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+{"id": "l-deprenyl-beagle-survival-1997", "name": "L-deprenyl 1 mg/kg daily versus placebo survival study in 82 paired beagles", "acronym": null, "kind": "controlled_trial", "status": "completed", "setting": null, "intervention": "L-deprenyl", "intervention_class": "drug", "comparator": "placebo", "dose_regimen": "1 mg/kg L-deprenyl orally once daily", "duration": "2 years and 10 weeks", "population": {"n": 82, "n_note": "82 beagles allotted to 41 pairs; elderly subset aged 10-15 years at start and treated for at least 6 months: 15 L-deprenyl and 18 placebo dogs", "breed": "beagle", "age": "2.8 to 16.4 years", "other": "Weight 6.3 to 15.8 kg"}, "primary_outcome": "Survivorship (survival to the conclusion of the study)", "result": "When survivorship for all dogs in the study was analyzed there was no significant difference between the L-deprenyl and placebo treated groups. In the subset of elderly dogs, dogs in the L-deprenyl group survived longer (p < 0.05) than dogs in the placebo group: twelve of 15 (80%) L-deprenyl dogs survived to the conclusion of the study, in contrast to only 7 of 18 (39%) of the dogs who received placebo (P=0.017).", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "9307048", "slug": null, "doi": "10.1016/s0024-3205(97)00611-5", "title": "Treatment with L-deprenyl prolongs life in elderly dogs.", "year": 1997, "role": "results", "quotes": ["Eighty two beagle dogs ranging in age from 2.8 to 16.4 years and in weight from 6.3 to 15.8 kg were allotted to 41 pairs and administered placebo or 1 mg/kg L-deprenyl orally once daily for 2 years and 10 weeks.", "When survivorship for all dogs in the study was analyzed there was no significant difference between the L-deprenyl and placebo treated groups", "To assess whether L-deprenyl treatment begun in later life might enhance canine longevity in a fashion similar to that documented in rodents we also examined survival in a subset of elderly dogs who were between the ages of 10 and 15 yrs at the start of tablet administration and who received tablets for at least 6 months.", "In this subset, dogs in the L-deprenyl group survived longer (p < 0.05) than dogs in the placebo group.", "Twelve of 15 (80%) dogs in the L-deprenyl group survived to the conclusion of the study, in contrast to only 7 of 18 (39%) of the dogs who received placebo (P=0.017).", "the findings reported herein suggest daily oral administration of 1 mg/kg L-deprenyl prolongs life when begun in relatively healthy dogs 10-15 years of age"], "quote_scope": "abstract"}], "summary": "Eighty-two beagles aged 2.8 to 16.4 years were allotted to 41 pairs and given placebo or 1 mg/kg L-deprenyl orally once daily for 2 years and 10 weeks. Across all dogs there was no significant difference in survivorship between the groups. In a subset of elderly dogs aged 10 to 15 years at the start who received tablets for at least 6 months, L-deprenyl-treated dogs survived longer (p < 0.05), with 12 of 15 surviving to the end of the study versus 7 of 18 on placebo (P=0.017).", "notes": "The abstract describes pair allotment and a placebo comparator but does not state randomization, blinding, the housing setting or the funder. The survival benefit is reported in an elderly subset analysed within the same study.", "parent_id": null, "tags": ["l-deprenyl", "lifespan", "beagle", "drug", "placebo-controlled"], "extracted_by": "claude-subagent-batch-A"}
+{"id": "selegiline-cds-open-label-2001", "name": "Selegiline hydrochloride (Anipryl) in dogs with cognitive dysfunction syndrome: noncomparative open-label study", "acronym": null, "kind": "single_arm_trial", "status": "completed", "setting": null, "intervention": "Selegiline hydrochloride (Anipryl), oral", "intervention_class": "drug", "comparator": "None (noncomparative open-label study)", "dose_regimen": "0.5 to 1.0 mg/kg orally once daily", "duration": "60 days", "population": {"n": 641, "n_note": "641 dogs treated", "breed": null, "age": null, "other": "Clinical signs consistent with canine cognitive dysfunction syndrome (CDS)"}, "primary_outcome": "Overall improvement and response by clinical sign on days 30 and 60; adverse events", "result": "Response to selegiline treatment on days 30 and 60 were similar. On day 60, 77.2% of dogs showed an overall improvement; response to treatment by clinical sign ranged from 67.8% (activity or sleep/wake cycle) to 77.8% (disorientation and interaction with family members). Diarrhea (4.2%), anorexia (3.6%), and vomiting/salivation (3.4%) were noted most frequently. Results of this study indicate the majority of the dogs with CDS responded to treatment with Anipryl by day 30.", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "19753696", "slug": null, "doi": null, "title": "A noncomparative open-label study evaluating the effect of selegiline hydrochloride in a clinical setting.", "year": 2001, "role": "results", "quotes": ["Six hundred forty-one dogs with clinical signs consistent with canine cognitive dysfunction syndrome (CDS) were treated orally with selegiline hydrochloride at 0.5 to 1.0 mg/kg once daily for 60 days.", "Response to selegiline treatment on days 30 and 60 were similar. On day 60, 77.2% of dogs showed an overall improvement; response to treatment by clinical sign ranged from 67.8% (activity or sleep/wake cycle) to 77.8% (disorientation and interaction with family members).", "All dogs enrolled in the study were monitored for possible adverse events; diarrhea (4.2%), anorexia (3.6%), and vomiting/salivation (3.4%) were noted most frequently.", "Results of this study indicate the majority of the dogs with CDS responded to treatment with Anipryl by day 30."], "quote_scope": "abstract"}], "summary": "In a single-arm open-label study, 641 dogs with clinical signs of canine cognitive dysfunction syndrome received oral selegiline hydrochloride at 0.5 to 1.0 mg/kg once daily for 60 days. Responses at days 30 and 60 were similar; on day 60, 77.2% of dogs showed overall improvement, with sign-specific response rates from 67.8% to 77.8%. Diarrhea (4.2%), anorexia (3.6%) and vomiting/salivation (3.4%) were the most frequent adverse events.", "notes": "Kind follows the title wording (noncomparative open-label study). The title places the study in a clinical setting, but the abstract does not state whether dogs were client-owned; sponsor not stated.", "parent_id": null, "tags": ["cognition", "drug", "selegiline", "cognitive-dysfunction", "open-label"], "extracted_by": "claude-subagent-batch-B"}
+{"id": "n6-n3-fatty-acids-vitamin-e-immune-geriatric-beagles-2003", "name": "Dietary n-6:n-3 fatty acid ratio and vitamin E on immune response and T cell subpopulations of healthy geriatric Beagles", "acronym": null, "kind": "controlled_trial", "status": "completed", "setting": null, "intervention": "Foods with low (1.4:1) or high (40:1) n-6 to n-3 fatty acid ratios in combination with three concentrations of all rac-alpha-tocopheryl acetate", "intervention_class": "diet_or_supplement", "comparator": "Factorial comparison across the diet groups (no separate untreated control stated)", "dose_regimen": "n-6 to n-3 fatty acid ratio 1.4:1 or 40:1; all rac-alpha-tocopheryl acetate low 17 mg/kg of food, medium 101 mg/kg, high 447 mg/kg; keyhole limpet hemocyanin inoculation at 13 and 15 weeks", "duration": "17 weeks", "population": {"n": 32, "n_note": null, "breed": "Beagle", "age": "7- to 10-year old", "other": "healthy female"}, "primary_outcome": "Immune functions and T cell subpopulations (percentages of CD8+ T cells, CD4+ to CD8+ ratio) and delayed-type hypersensitivity (DTH) skin test response", "result": "After 12 weeks, dogs consuming low concentrations of alpha-tocopheryl acetate had lower percentages of CD8+ T cells and higher CD4+ to CD8+ ratios than dogs on medium or high concentrations; dogs consuming low n-3 fatty acids with medium alpha-tocopheryl acetate had the largest DTH response. The authors conclude that an optimum amount of dietary alpha-tocopheryl acetate, regardless of the n-6 to n-3 ratio, stimulates the CD8+ T cell population, and that its effects on the DTH response are blunted by dietary n-3 fatty acids.", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "12828263", "slug": null, "doi": "10.2460/ajvr.2003.64.762", "title": "Effects of dietary n-6 and n-3 fatty acids and vitamin E on the immune response of healthy geriatric dogs.", "year": 2003, "role": "results", "quotes": ["To determine the effect of dietary n-6 to n-3 fatty acid ratios and alpha-tocopheryl acetate concentration on immune functions andT cell subpopulations in healthy dogs.", "Thirty-two 7- to 10-year old female Beagles.", "For 17 weeks, dogs were fed food that contained low (1.4:1) or high (40:1) ratios of n-6 to n-3 fatty acids in combination with 3 concentrations of all rac-alpha-tocopheryl acetate (low, 17 mg/kg of food; medium, 101 mg/kg; high, 447 mg/kg).", "Dogs were inoculated twice with a keyhole limpet hemocyanin suspension at 13 and 15 weeks.", "After 12 weeks, dogs consuming low concentrations of alpha-tocopheryl acetate had lower percentages of CD8+ T cells, compared with dogs consuming medium or high alpha-tocopheryl acetate concentrations. Also, dogs consuming low alpha-tocopheryl acetate concentrations had higher CD4+ to CD8+ T cell ratios.", "Dogs consuming low concentrations of n-3 fatty acids with medium concentrations of alpha-tocopheryl acetate had the largest delayed-type hypersensitivity (DTH) skin test response.", "An optimum amount of dietary alpha-tocopheryl acetate concentration, regardless of the dietary n-6 to n-3 fatty acid ratio, stimulates the CD8+ T cell population. Effects of an optimum amount of dietary alpha-tocopheryl acetate concentration on the DTH response are blunted by dietary n-3 fatty acids."], "quote_scope": "abstract"}], "summary": "Thirty-two healthy female Beagles aged 7 to 10 years were fed for 17 weeks foods combining a low (1.4:1) or high (40:1) n-6 to n-3 fatty acid ratio with low, medium or high alpha-tocopheryl acetate, and were inoculated with keyhole limpet hemocyanin at weeks 13 and 15, to determine effects on immune function and T cell subpopulations. Dogs on low vitamin E had lower CD8+ T cell percentages and higher CD4+:CD8+ ratios than dogs on medium or high vitamin E, and the largest DTH skin response occurred with low n-3 and medium vitamin E. The authors conclude an optimum vitamin E level stimulates CD8+ T cells regardless of fatty acid ratio, while n-3 fatty acids blunt its effect on DTH.", "notes": "Borderline inclusion: the abstract objective names immune function in healthy dogs rather than aging, but the title and the 7- to 10-year-old geriatric population place it in the immunosenescence context. The abstract does not describe randomization; the PubMed publication type lists Randomized Controlled Trial. No full text in the corpus.", "parent_id": null, "tags": ["diet", "vitamin-e", "omega-3", "immunosenescence", "t-cells", "beagle"], "extracted_by": "claude-subagent-batch-C"}
+{"id": "beagle-antioxidant-cofactor-landmark-discrimination-2004", "name": "Prior experience, antioxidants and mitochondrial cofactors in aged beagles (landmark discrimination)", "acronym": null, "kind": "randomized_controlled_trial", "status": "completed", "setting": null, "intervention": "Food providing higher levels of vitamin E (antioxidants and mitochondrial cofactors)", "intervention_class": "diet_or_supplement", "comparator": null, "dose_regimen": null, "duration": null, "population": {"n": null, "n_note": null, "breed": null, "age": "aged dogs", "other": null}, "primary_outcome": "Performance on landmark-discrimination tasks; serum vitamin E concentrations", "result": "providing higher levels of vitamin E in food resulted in higher serum vitamin E concentrations and improved performance on landmark-discrimination tasks in aged dogs. Factors other than vitamin E also contributed to the response but remain undefined.", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "15150725", "slug": null, "doi": null, "title": "Prior experience, antioxidants, and mitochondrial cofactors improve cognitive function in aged beagles.", "year": 2004, "role": "results", "quotes": ["Results of this study support the free-radical theory of aging and demonstrated that providing higher levels of vitamin E in food resulted in higher serum vitamin E concentrations and improved performance on landmark-discrimination tasks in aged dogs.", "Factors other than vitamin E also contributed to the response but remain undefined."], "quote_scope": "abstract"}], "summary": "This study fed aged dogs food providing higher levels of vitamin E and tested them on landmark-discrimination tasks. Higher dietary vitamin E produced higher serum vitamin E concentrations and improved landmark-discrimination performance, although factors other than vitamin E also contributed to the response. The published abstract gives no sample size, dose, duration or comparator.", "notes": "The abstract is a two-sentence summary. Kind is recorded as randomized_controlled_trial from the PubMed publication type (Randomized Controlled Trial; Clinical Trial); the title names prior experience, antioxidants and mitochondrial cofactors in aged beagles, so breed is Beagle by title only. Judged separate from the long-term antioxidant/enrichment longitudinal study because it reports landmark-discrimination and serum vitamin E outcomes not described in that study's reports; merge if other sources show it is the same cohort.", "parent_id": null, "tags": ["cognition", "antioxidant-diet", "vitamin-e", "beagle"], "extracted_by": "claude-subagent-batch-B"}
+{"id": "ginseng-brewers-yeast-gerivet-geriatric-dogs-2007", "name": "Panax Ginseng with brewers' yeast (Gerivet) as a stimulant for geriatric dogs", "acronym": null, "kind": "randomized_controlled_trial", "status": "completed", "setting": "client_owned", "intervention": "Ginseng (Panax Ginseng) together with brewers' yeast (Saccharomyces cerevisae)", "intervention_class": "diet_or_supplement", "comparator": "Brewers' yeast only (control group, but not a true placebo); an external group was also used for comparison", "dose_regimen": null, "duration": "8 weeks of treatment, with follow-up at 12 and 16 weeks", "population": {"n": 80, "n_note": "Ginseng plus yeast n = 41; yeast-only control n = 39", "breed": null, "age": null, "other": null}, "primary_outcome": "Owner questionnaire and three visual analogue scales: seven primary (mental) outcome measures and secondary (physical) outcome measures, as change from baseline", "result": "Panax Ginseng plus yeast significantly improved all evaluated variables within the group. Four of the seven primary (mentally) outcome measures were significant when comparing the changes in the Ginseng group with the control group, and six of the seven were significant when compared to an external group. As the secondary (physical) outcome measures were significantly better in both the Ginseng and the control group compared to the external group, it indicates that brewers' yeast is the ingredient that has impact on physical performance. No significant changes in blood- or urine analyses and no side effects were seen.", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "17610402", "slug": null, "doi": "10.1111/j.1365-2885.2007.00876.x", "title": "Panax Ginseng in combination with brewers' yeast (Gerivet) as a stimulant for geriatric dogs: a controlled-randomized blinded study.", "year": 2007, "role": "results", "quotes": ["The study was performed on two groups of dogs, one (n = 41) given Ginseng (Panax Ginseng) together with brewers' yeast (Saccharomyces cerevisae) and the other (n = 39) given only brewers' yeast (control group, but not a true placebo), for 8 weeks.", "Using a questionnaire and three visual analogue scales, the blinded owners evaluated the dogs before the trial, weekly for the 8 weeks of the trial and twice, at 12th and 16th weeks, after the trial (follow-up).", "The changes from baseline to the end of the treatment period in the variable scores were calculated for each dog and used in statistics.", "Panax Ginseng plus yeast significantly improved all evaluated variables within the group. Four of the seven primary (mentally) outcome measures were significant when comparing the changes in the Ginseng group with the control group, and six of the seven were significant when compared to an external group.", "As the secondary (physical) outcome measures were significantly better in both the Ginseng and the control group compared to the external group, it indicates that brewers' yeast is the ingredient that has impact on physical performance. No significant changes in blood- or urine analyses and no side effects were seen."], "quote_scope": "abstract"}], "summary": "Eighty dogs were given either Panax Ginseng with brewers' yeast (n = 41) or brewers' yeast alone as a non-placebo control (n = 39) for 8 weeks, with blinded owners scoring a questionnaire and three visual analogue scales weekly and at 12 and 16 weeks of follow-up. Ginseng plus yeast improved all variables within its group; four of seven primary mental measures were significantly better than the control group and six of seven better than an external group. Physical measures improved in both treated groups relative to the external group, attributed to the yeast, and no side effects or blood or urine changes were seen.", "notes": "Kind is recorded as randomized_controlled_trial from the title (controlled-randomized blinded study) and PubMed publication type; the abstract describes blinded owners and a control group that was not a true placebo. The title describes the dogs as geriatric and names the product Gerivet; the abstract gives no ages or dose.", "parent_id": null, "tags": ["cognition", "nutraceutical", "ginseng", "geriatric", "client-owned"], "extracted_by": "claude-subagent-batch-B"}
+{"id": "beagle-phosphatidylserine-ginkgo-nutraceutical-crossover-2008", "name": "Nutraceutical supplement (phosphatidylserine, Ginkgo biloba, vitamin E, pyridoxine) for short-term memory in aged beagles", "acronym": null, "kind": "crossover_trial", "status": "completed", "setting": null, "intervention": "Commercially available nutraceutical supplement containing phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine", "intervention_class": "diet_or_supplement", "comparator": "Control substance", "dose_regimen": null, "duration": null, "population": {"n": 9, "n_note": "9 aged beagles tested; split into two groups for the crossover phases", "breed": "Beagle", "age": "aged", "other": null}, "primary_outcome": "Performance accuracy on a delayed-non-matching-to-position task (short-term visuospatial memory)", "result": "Performance accuracy was significantly improved in supplemented dogs compared with control dogs and the effect was long lasting.", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "18481547", "slug": null, "doi": null, "title": "Improvement of short-term memory performance in aged beagles by a nutraceutical supplement containing phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine.", "year": 2008, "role": "results", "quotes": ["The purpose of the present study was to examine if a commercially available nutraceutical supplement that may be neuroprotective and contains phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine could improve cognitive function in aged beagles.", "Nine aged beagles were tested on performance on a delayed-non-matching-to-position task, which is a neuropsychological test of short-term visuospatial memory.", "All subjects were tested on 5 baseline sessions; then, to assess the supplement, a crossover design was used in which 1 group received the supplement and the other a control substance in the 1st phase, with treatment conditions being reversed in the 2nd phase.", "Performance accuracy was significantly improved in supplemented dogs compared with control dogs and the effect was long lasting."], "quote_scope": "abstract"}], "summary": "Nine aged beagles were tested on a delayed-non-matching-to-position task of short-term visuospatial memory, then given a commercial nutraceutical containing phosphatidylserine, Ginkgo biloba, vitamin E and pyridoxine or a control substance in a two-phase crossover design. Performance accuracy was significantly improved in supplemented dogs compared with controls, and the effect was long lasting. Dose and phase duration are not given in the abstract.", "notes": "Dose, phase duration, setting and funding are not stated in the abstract.", "parent_id": null, "tags": ["cognition", "nutraceutical", "beagle", "memory", "crossover"], "extracted_by": "claude-subagent-batch-B"}
+{"id": "same-cognitive-decline-rct-2008", "name": "S-adenosylmethionine (Novifit) for age-related mental decline in dogs: double-blinded placebo-controlled trial", "acronym": null, "kind": "randomized_controlled_trial", "status": "completed", "setting": null, "intervention": "Oral S-adenosylmethionine (SAMe) tosylate tablets (Novifit tablets, Virbac)", "intervention_class": "diet_or_supplement", "comparator": "Identical placebo tablets", "dose_regimen": "18 mg/kg SAMe tosylate, oral tablets, for 2 months", "duration": "2 months", "population": {"n": 36, "n_note": "36 dogs: SAMe n=17, placebo n=19", "breed": null, "age": "older than 8 years", "other": "Signs of cognitive dysfunction for at least 1 month; concurrent behavioral treatment forbidden"}, "primary_outcome": "14-item standardized questionnaire evaluating behavior and locomotion difficulties (activity, awareness, aggregate mental impairment score)", "result": "Compared with the placebo group, SAMe-treated dogs showed greater improvement in activity (41.7% versus 2.6% after 4 weeks, P<.0003; 57.1% versus 9.0% after 8 weeks, P<.003) and awareness (33.3% versus 17.9% after 4 weeks, P<.05; 59.5% versus 21.4% after 8 weeks, P<.01). The aggregate mental impairment score was reduced by more than 50% in 41.2% and 15.8% of dogs treated with SAMe and placebo, respectively, at week 8. SAMe tosylate tablets proved safe and effective in improving signs of age-related mental decline in dogs.", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "18597245", "slug": null, "doi": null, "title": "Effect of S-adenosylmethionine tablets on the reduction of age-related mental decline in dogs: a double-blinded, placebo-controlled trial.", "year": 2008, "role": "results", "quotes": ["Oral S-adenosylmethionine (SAMe) tosylate supplementation (Novifit tablets, Virbac) was evaluated as a dietary aid for the management of age-related mental impairment in dogs.", "Thirty-six dogs older than 8 years that had displayed signs of cognitive dysfunction for at least 1 month were selected for the study. The dogs were administered 18 mg/kg SAMe tosylate (n=17) or identical placebo tablets (n=19) for 2 months. Concurrent behavioral treatment was forbidden.", "A 14-item standardized questionnaire evaluated behavior and locomotion difficulties.", "Compared with the placebo group, SAMe-treated dogs showed greater improvement in activity (41.7% versus 2.6% after 4 weeks, P<.0003; 57.1% versus 9.0% after 8 weeks, P<.003) and awareness (33.3% versus 17.9% after 4 weeks, P<.05; 59.5% versus 21.4% after 8 weeks, P<.01).", "The aggregate mental impairment score was reduced by more than 50% in 41.2% and 15.8% of dogs treated with SAMe and placebo, respectively, at week 8. SAMe tosylate tablets proved safe and effective in improving signs of age-related mental decline in dogs."], "quote_scope": "abstract"}], "summary": "Thirty-six dogs older than 8 years with at least one month of cognitive dysfunction signs received 18 mg/kg oral SAMe tosylate (n=17) or identical placebo tablets (n=19) for 2 months, with behavior and locomotion scored on a 14-item questionnaire. SAMe-treated dogs improved more than placebo in activity and awareness at 4 and 8 weeks, and 41.2% versus 15.8% had their aggregate mental impairment score reduced by more than half at week 8. The authors conclude SAMe tosylate tablets were safe and effective for signs of age-related mental decline.", "notes": "Kind is recorded as randomized_controlled_trial from the title (double-blinded, placebo-controlled trial) and the PubMed publication type; the abstract does not describe the randomization procedure. The product was supplied as Novifit tablets (Virbac); sponsor and setting are not stated.", "parent_id": null, "tags": ["cognition", "nutraceutical", "same", "cognitive-dysfunction", "placebo-controlled"], "extracted_by": "claude-subagent-batch-B"}
+{"id": "beagle-antioxidant-diet-behavioral-enrichment", "name": "Antioxidant-fortified diet and behavioral enrichment in aged beagles (longitudinal study)", "acronym": null, "kind": "controlled_trial", "status": "completed", "setting": null, "intervention": "Antioxidant-fortified food (a broad spectrum of antioxidants and mitochondrial enzymatic cofactors) and a program of behavioral enrichment (increased exercise, environmental enrichment, and a series of learning tasks), alone and combined in a 2 x 2 factorial design", "intervention_class": "combination", "comparator": "Control food and control (normal level) environment", "dose_regimen": null, "duration": "2-year longitudinal study; cognitive testing after 6 months, 1 year and 2 years of treatment", "population": {"n": 48, "n_note": "48 aged dogs assigned to four groups of 12 (CC, CE, AC, AE); two additional groups of young behaviorally enriched dogs (control or fortified food); the immune sub-analysis reports n=21 geriatric dogs", "breed": "Beagle", "age": "9-12 years (aged groups)", "other": "Aged groups were formed as cognitively equivalent from baseline performance on a battery of cognitive tests"}, "primary_outcome": "Discrimination and reversal learning (oddity discrimination after 6 months; size discrimination and reversal after 1 year; black/white discrimination after 2 years); neutrophil phagocytosis and lymphocyte proliferation in an immune sub-analysis", "result": "At one and two years, the aged combined treatment group showed more accurate learning than the other aged groups. Discrimination learning was significantly improved by behavioral enrichment. Reversal learning was improved by both behavioral enrichment and dietary fortification. By contrast, the fortified food had no effect on the young dogs. In the immune sub-analysis, neutrophil phagocytosis was significantly increased in dogs receiving both dietary antioxidants and cognitive enrichment.", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "12392778", "slug": null, "doi": "10.1016/s0197-4580(02)00020-9", "title": "Dietary enrichment counteracts age-associated cognitive dysfunction in canines.", "year": 2002, "role": "results", "quotes": ["we studied the effects of dietary antioxidants and age in a canine model of aging that parallels the key features of cognitive decline and neuropathology in humans", "Old and young animals were placed on either a standard control food, or a food enriched with a broad spectrum of antioxidants and mitochondrial enzymatic cofactors.", "After 6 months of treatment, the animals were tested on four increasingly difficult oddity discrimination learning problems.", "However, this age-associated decline was reduced in the animals fed the enriched food, particularly on the more difficult tasks."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "15130670", "slug": null, "doi": "10.1016/j.exger.2004.01.007", "title": "Long-term treatment with antioxidants and a program of behavioral enrichment reduces age-dependent impairment in discrimination and reversal learning in beagle dogs.", "year": 2004, "role": "design", "quotes": ["The effects of long-term treatment with both antioxidants and a program of behavioral enrichment were studied as part of a longitudinal investigation of cognitive aging in beagle dogs.", "Baseline performance on a battery of cognitive tests was used to assign 48 aged dogs (9-12 years) into four cognitively equivalent groups, of 12 animals per group: Group CC (control food-control environment), group CE (control food-enriched environment); Group AC (antioxidant fortified food-control environment); Group AE (fortified food-enriched environment).", "We also tested a group of young dogs fed the control food and a second group fed the fortified food. Both groups of young dogs received a program of behavioral enrichment.", "To evaluate the effects of the interventions on cognition after 1 year, the dogs were tested on a size discrimination learning task and subsequently on a size discrimination reversal learning task.", "Both tasks were also improved by both the fortified food and the behavioral enrichment. However, in both instances the treatment effects largely reflected improved performance in the combined treatment group."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "15585348", "slug": null, "doi": "10.1016/j.neurobiolaging.2004.02.014", "title": "Learning ability in aged beagle dogs is preserved by behavioral enrichment and dietary fortification: a two-year longitudinal study.", "year": 2005, "role": "results", "quotes": ["The effectiveness of two interventions, dietary fortification with antioxidants and a program of behavioral enrichment, was assessed in a longitudinal study of cognitive aging in beagle dogs.", "Discrimination learning and reversal was assessed after one year of treatment with a size discrimination task, and again after two years with a black/white discrimination task.", "At one and two years, the aged combined treatment group showed more accurate learning than the other aged groups. Discrimination learning was significantly improved by behavioral enrichment. Reversal learning was improved by both behavioral enrichment and dietary fortification. By contrast, the fortified food had no effect on the young dogs.", "These results suggest that behavioral enrichment or dietary fortification with antioxidants over a long-duration can slow age-dependent cognitive decline, and that the two treatments together are more effective than either alone in older dogs."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "16806493", "slug": null, "doi": "10.1016/j.vetimm.2006.03.019", "title": "Dietary antioxidants and behavioral enrichment enhance neutrophil phagocytosis in geriatric Beagles.", "year": 2006, "role": "sub-analysis", "quotes": ["The study objective was to determine the effects of feeding food enriched in antioxidants and a program of environmental/cognitive enrichment on selected ex vivo assays of inflammatory and immune cells in healthy geriatric Beagle dogs (n=21).", "Four groups of dogs were tested using a 2 x 2 factorial design. The 2-year longitudinal study included both nutritional (control food or antioxidant-fortified food) and behavioral (normal level or cognitive enrichment) interventions. Behavior enrichment included increased exercise, environmental enrichment, and a series of learning tasks.", "Phagocytosis of opsonized latex-coated beads by peripheral blood neutrophils was measured by flow cytometry and found to be significantly increased in dogs receiving both dietary antioxidants and cognitive enrichment."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "17717087", "slug": null, "doi": "10.1196/annals.1396.004", "title": "Combining an antioxidant-fortified diet with behavioral enrichment leads to cognitive improvement and reduced brain pathology in aging canines: strategies for healthy aging.", "year": 2007, "role": "review", "quotes": ["We present additional evidence that, in a canine model of aging, combining an antioxidant-enriched diet and behavioral enrichment (including social, physical, and cognitive components) can lead to substantial improvements in cognition and reduced brain pathology."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "19714491", "slug": null, "doi": "10.1007/s11357-008-9063-2", "title": "Strategies for improving cognition with aging: insights from a longitudinal study of antioxidant and behavioral enrichment in canines.", "year": 2009, "role": "review", "quotes": ["Here we review the results of an intervention study using a canine model of human aging. The study was unique in that it compared the effects of dietary antioxidant supplementation alone and in combination with behavioral enrichment.", "We found that both interventions lead to improvements in cognitive ability in aged dogs; however, combining the treatments preserved cognition to a greater extent than either treatment alone."], "quote_scope": "abstract"}], "summary": "A longitudinal controlled study in beagles tested an antioxidant-fortified food and a program of behavioral enrichment, alone and combined, against control food and a control environment in a 2 x 2 factorial design. Forty-eight aged dogs (9-12 years) were assigned from baseline cognitive scores into four cognitively equivalent groups of 12, with additional groups of young dogs. Discrimination and reversal learning were tested after 6 months, 1 year and 2 years of treatment; the combined-treatment group learned more accurately than the other aged groups at one and two years, enrichment improved discrimination learning, and both treatments improved reversal learning. An immune sub-analysis of 21 dogs found neutrophil phagocytosis significantly increased in dogs receiving both treatments.", "notes": "Grouped as one study: the 2004 and 2005 papers report the 1-year and 2-year cognitive results of the same longitudinal investigation, the 2006 paper reports an immune sub-analysis of its 2-year cohort (n=21), and the 2007 and 2009 reviews summarise the same intervention study. The 2002 paper reports the 6-month oddity-discrimination results in old and young dogs fed the same antioxidant-fortified food; its abstract does not mention the enrichment arm. Groups were formed as cognitively equivalent from baseline scores and randomization is not stated, so kind is recorded as controlled_trial. Setting, dose, funding and study dates are not stated in the abstracts.", "parent_id": null, "tags": ["cognition", "antioxidant-diet", "enrichment", "beagle", "immunosenescence", "longitudinal"], "extracted_by": "claude-subagent-batch-B"}
+{"id": "purina-lifetime-diet-restriction", "name": "Lifetime 25% diet restriction paired-feeding study in 48 Labrador Retrievers", "acronym": null, "kind": "randomized_controlled_trial", "status": "completed", "setting": null, "intervention": "25% diet restriction (each restricted dog fed 75% of the food consumed by its control-fed pair mate; same diet, only the quantity differed)", "intervention_class": "diet_restriction", "comparator": "Control-fed (CF) pair mate", "dose_regimen": "25% less food than the pair-mate (75% of the total food consumed by the control-fed pair mate); feeding began at age 8 weeks", "duration": "From 8 weeks of age until death (lifetime); body composition measured annually until 12 years of age; immune parameters monitored from 4 to 13 years", "population": {"n": 48, "n_note": "48 dogs from seven litters, paired at 6 weeks by sex and weight and allotted to 2 groups of 24 (diet-restricted and control-fed)", "breed": "Labrador Retriever", "age": "Paired at age 6 weeks; feeding protocol from 8 weeks of age until death", "other": "Puppies from 7 litters; weight- and sex-matched pairs"}, "primary_outcome": "Life span (median: age when 50% of dogs deceased; maximum: age when 90% deceased), age at onset of chronic disease, and markers of aging (serum biochemistry, body condition, body composition)", "result": "Median life span was significantly longer for dogs in which food was restricted (1.8 years longer median lifespan among diet-restricted dogs), and the onset of clinical signs of chronic disease generally was delayed, especially osteoarthritis. CR retarded age-related declines in lymphoproliferative responses and lymphocyte subsets. No differences in prevalence or severity of radiographic and histopathologic elbow OA were found between feeding groups; long-term DR did not negatively affect skeletal maturation, structure or metabolism.", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "11991408", "slug": null, "doi": "10.2460/javma.2002.220.1315", "title": "Effects of diet restriction on life span and age-related changes in dogs.", "year": 2002, "role": "results", "quotes": ["To evaluate the effects of 25% diet restriction on life span of dogs and on markers of aging.", "Paired feeding study.", "48 Labrador Retrievers.", "Dogs were paired, and 1 dog in each pair was fed 25% less food than its pair-mate from 8 weeks of age until death.", "Serum biochemical analyses were performed, body condition was scored, and body composition was measured annually until 12 years of age.", "Age at onset of chronic disease and median (age when 50% of the dogs were deceased) and maximum (age when 90% of the dogs were deceased) life spans were evaluated.", "Compared with control dogs, food-restricted dogs weighed less and had lower body fat content and lower serum triglycerides, triiodothyronine, insulin, and glucose concentrations.", "Median life span was significantly longer for dogs in which food was restricted.", "The onset of clinical signs of chronic disease generally was delayed for food-restricted dogs.", "Results suggest that 25% restriction in food intake increased median life span and delayed the onset of signs of chronic disease in these dogs."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "18062831", "slug": null, "doi": "10.1017/s0007114507871686", "title": "Diet restriction and ageing in the dog: major observations over two decades.", "year": 2008, "role": "follow-up", "quotes": ["This report reviews decade two of the lifetime diet restriction study of the dog.", "Labrador retrievers (n 48) were paired at age 6 weeks by sex and weight within each of seven litters, and assigned randomly within the pair to control-feeding (CF) or 25 % diet restriction (DR).", "Feeding began at age 8 weeks. The same diet was fed to all dogs; only the quantity differed.", "Major lifetime observations included 1.8 years longer median lifespan among diet-restricted dogs, with delayed onset of late life diseases, especially osteoarthritis.", "Long-term DR did not negatively affect skeletal maturation, structure or metabolism.", "Fat mass above 25 % was associated with increasing insulin resistance, which independently predicted lifespan and chronic diseases.", "diet-restricted dogs required 17 % less energy to maintain each lean kilogram.", "Independent of feeding group, increased hazard of earlier death was associated with lower lymphoproliferative responses to phytohaemagglutinin, concanavalin A, and pokeweed mitogen; lower total lymphocytes, T-cells, CD4 and CD8 cells; lower CD8 percentages and higher B-cell percentages."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "16567002", "slug": null, "doi": "10.1016/j.vetimm.2006.02.002", "title": "Modulation of canine immunosenescence by life-long caloric restriction.", "year": 2006, "role": "sub-analysis", "quotes": ["Longitudinal effects of CR on the canine immune system are presented in this report.", "A group of 48 Labrador Retrievers, divided at weaning into weight- and sex-matched pairs, were maintained on a diet restriction protocol from age 8 weeks until death.", "Each restricted dog received 75% of the total food consumed by its control-fed pair mate.", "Immune parameters were monitored from 4 to 13 years.", "CR retarded age-related declines in both lymphoproliferative responses and absolute numbers of lymphocytes and the T, CD4, and CD8-cell subsets.", "No direct effect of CR on phagocytic activity of PMN, antibody production or NK cell activity, was observed.", "Lower lymphoproliferative responses, lower numbers of lymphocytes, T, CD4 and CD8 cells, lower CD8 percentages and higher B-cell percentages were all found to be significantly associated with a decreased likelihood of survival in these dogs."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "19236677", "slug": null, "doi": "10.1111/j.1532-950x.2008.00487.x", "title": "A longitudinal study of the influence of lifetime food restriction on development of osteoarthritis in the canine elbow.", "year": 2009, "role": "sub-analysis", "quotes": ["To report the effects of age and lifetime calorie restriction on development and progression of osteoarthritis (OA) in elbow joints of Labrador retrievers.", "Labrador retriever dogs (n=48).", "Puppies from 7 litters were allotted to 2 groups of 24 dogs each. Diet-restricted (DR) dogs received 25% fewer calories than control-fed (CF) pair mates.", "Elbow radiographs were taken at 6 and 8 years of age and end of life (EOL).", "Radiographic OA severity was greater for CF dogs at 6 years only (P<.05).", "No differences in prevalence or severity of radiographic and histopathologic elbow OA were found between feeding groups. Diet restriction resulted in a 1.8-year extension in median lifespan but no additional incremental worsening of elbow disease."], "quote_scope": "abstract"}], "summary": "Forty-eight Labrador Retrievers from seven litters were paired by sex and weight, and one dog in each pair was randomly assigned to receive 25% less food than its control-fed pair mate from 8 weeks of age until death. Median life span was significantly longer in the diet-restricted dogs (1.8 years longer), and the onset of clinical signs of chronic disease, especially osteoarthritis, was delayed. Diet restriction also retarded age-related declines in lymphoproliferative responses and lymphocyte subsets and did not negatively affect skeletal maturation, while elbow osteoarthritis prevalence and severity did not differ between feeding groups.", "notes": "Four papers report one lifetime study: the 2002 JAVMA results paper, the 2006 immunosenescence sub-analysis, the 2008 two-decade review and the 2009 elbow osteoarthritis sub-analysis. The abstracts do not name the sponsoring organization, the housing setting or the calendar years; the slug follows the registry's working name for the study.", "parent_id": null, "tags": ["diet-restriction", "lifespan", "labrador-retriever", "immunosenescence", "osteoarthritis", "body-composition"], "extracted_by": "claude-subagent-batch-A"}
+{"id": "skn-cell-therapy-canine-cognitive-dysfunction-sydney-2022", "name": "Autologous skin-derived neural precursor (SKN) cell therapy for canine cognitive dysfunction in older companion dogs (DOGS + CELLS trial)", "acronym": "DOGS + CELLS", "kind": "single_arm_trial", "status": "completed", "setting": "client_owned", "intervention": "Direct microinjection of autologous skin-derived neuroprecursors (SKNs) into the bilateral hippocampus using MRI-guided stereotaxis", "intervention_class": "cell_or_gene_therapy", "comparator": "None (open-label, no control arm); post-mortem histology compared with a brain bank (N = 12) of untreated aged dogs", "dose_regimen": "250,000 autologous SKNs microinjected into the bilateral hippocampus", "duration": "3-month primary endpoint; clinical follow-up up to 2 years", "population": {"n": 6, "n_note": "N = 8 recruited and N = 6 treated over 8 years; modified intention-to-treat analysis N = 5", "breed": null, "age": "aged 10-16 years", "other": "older companion (community-dwelling) dogs with definitive diagnosis of Canine Cognitive Dysfunction (CCD); 2 female, 4 male"}, "primary_outcome": "Change in the Canine Cognitive Dysfunction Rating Scale (CCDR) from baseline to 3 months post treatment; safety assessed clinically", "result": "Four out-of-five dogs improved on the primary clinical CCDR endpoint, three fell below diagnostic threshold, and two underwent full syndromal reversal lasting up to 2 years (modified ITT paired T test = 3.06, df = 4, p = 0.038). At post mortem, hippocampal synaptic density was nine standard deviations above non-treated dogs. There was no impact on AD pathology or long-term safety signals; one patient had a surgical adverse event requiring euthanasia.", "lead_organization": "University of Sydney", "sponsor_or_funder": null, "registration": [{"registry": "preclinicaltrials.eu", "id": "PCTE0000169", "url": null}], "start_year": 2012, "end_year": 2020, "sources": [{"type": "pmid", "pmid": "35715872", "slug": null, "doi": "10.1186/s13287-022-02933-w", "title": "Autologous skin-derived neural precursor cell therapy reverses canine Alzheimer dementia-like syndrome in a proof of concept veterinary trial.", "year": 2022, "role": "results", "quotes": ["Older companion dogs naturally develop a dementia-like syndrome with biological, clinical and therapeutic similarities to Alzheimer disease (AD).", "A Phase 1/2A veterinary trial was conducted in N = 6 older companion dogs with definitive diagnosis of Canine Cognitive Dysfunction (CCD).", "Treatment comprised direct microinjection of 250,000 autologous skin-derived neuroprecursors (SKNs) into the bilateral hippocampus using MRI-guided stereotaxis.", "Safety was assessed clinically and efficacy using the validated Canine Cognitive Dysfunction Rating Scale (CCDR) at baseline and 3-month post treatment.", "Intention to treat analysis imputed a single patient that had a surgical adverse event requiring euthanasia.", "these were compared to a brain bank (N = 12) of untreated aged dogs with and without CCD", "Four out-of-five dogs improved on the primary clinical CCDR endpoint, three fell below diagnostic threshold, and remarkably, two underwent full syndromal reversal lasting up to 2 years.", "At post mortem, synaptic density in the hippocampus specifically was nine standard deviations above non-treated dogs, and intensity of new neurons also several fold higher.", "There was no impact on AD pathology or long-term safety signals."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "35715872", "slug": null, "doi": "10.1186/s13287-022-02933-w", "title": "Autologous skin-derived neural precursor cell therapy reverses canine Alzheimer dementia-like syndrome in a proof of concept veterinary trial.", "year": 2022, "role": "design", "quotes": ["This trial was approved by the University of Sydney Animal Ethics Committee, and because it spanned 8 years (2012–2020) the trial encompassed several protocol updates.", "diagnosed in aged companion dogs (*N* = 6, 2 female, 4 male, aged 10–16 years", "The trial was designed to PREPARE guidelines, including protocol registration PCTE0000169 on www.preclinicaltrial.eu", "Over an 8-year period, we recruited *N* = 8 and treated *N* = 6 community-dwelling CCD dogs in the DOGS + CELLS trial (University of Sydney Animal Ethics Committee #2019/1612).", "Modified intention-to-treat ITT analysis (*N* = 5) found a significant improvement on the trial’s primary endpoint", "Modified ITT analysis: Paired *T* test = 3.06, *df* = 4, *p* = 0.038.", "An open-label design was used in this veterinary trial for the same reason it is commonly employed in first-in-human cell therapy trials [45]: CCD is a progressive and terminal disorder and surgical delivery encompasses some risk; it was considered ethically inappropriate to employ an inert control arm."], "quote_scope": "fulltext"}], "summary": "An open-label Phase 1/2A veterinary trial at the University of Sydney, run over 2012-2020, treated six older companion dogs (aged 10-16 years) with a definitive diagnosis of canine cognitive dysfunction by MRI-guided microinjection of 250,000 autologous skin-derived neural precursor cells into both hippocampi. The primary endpoint was change in the CCDR scale at 3 months. Four of five evaluable dogs improved, three fell below the diagnostic threshold and two showed full syndromal reversal lasting up to 2 years; one dog had a surgical adverse event requiring euthanasia, and post-mortem hippocampal synaptic density was far above untreated dogs.", "notes": "Borderline on framing: the authors present this as treatment of a canine Alzheimer dementia-like syndrome (CCD) in older dogs; included because CCD is the age-related cognitive decline of dogs. Single-arm, open-label, with no control arm; a companion aged-rat study is reported in the same paper. No funding statement located in the full text.", "parent_id": null, "tags": ["stem-cells", "cell-therapy", "cognition", "ccd", "hippocampus", "surgery"], "extracted_by": "claude-subagent-batch-C"}
+{"id": "golden-retriever-lifetime-study", "name": "Golden Retriever Lifetime Study (Morris Animal Foundation)", "acronym": "GRLS", "kind": "longitudinal_cohort", "status": "ongoing", "setting": "client_owned", "intervention": null, "intervention_class": "none", "comparator": null, "dose_regimen": null, "duration": "lifetime follow-up; baseline enrolment June 2012 to April 2015", "population": {"n": 3044, "n_note": "completed baseline enrolment; as of 31 May 2021, 2,251 engaged, 352 died, 441 lost to follow-up", "breed": "Golden Retriever", "age": "6 months to 2 years at enrolment", "other": "United States"}, "primary_outcome": "incidence of hemangiosarcoma, lymphoma, osteosarcoma and high-grade mast cell tumors; secondary outcomes include other cancers, hypothyroidism, epilepsy, atopy, otitis externa, hip dysplasia, heart failure and renal failure", "result": null, "lead_organization": "Morris Animal Foundation", "sponsor_or_funder": "Morris Animal Foundation", "registration": [], "start_year": 2012, "end_year": null, "sources": [{"type": "europepmc", "pmid": "35679242", "slug": null, "doi": "10.1371/journal.pone.0269425", "title": "Cohort profile: The Golden Retriever Lifetime Study (GRLS).", "year": 2022, "role": "design", "quotes": ["a prospective cohort study investigating nutritional, environmental, lifestyle, and genetic risk factors for cancer and other common diseases in dogs.", "Primary outcomes of interest include hemangiosarcoma, lymphoma, osteosarcoma, and high-grade mast cell tumors.", "A total of 3,044 United States Golden Retrievers aged 6 months to 2 years completed baseline enrollment from June 2012 to April 2015.", "As of May 31, 2021, 2,251 dogs remain engaged in the study, 352 have died, and 441 are lost to follow-up.", "Extensive annual questionnaires completed by owners and veterinarians gather information about lifestyle, environmental exposures, physical activity, reproductive history, behavior, diet, medications, and diagnoses.", "Questionnaire data are freely available to researchers with approved credentials who agree to a data use agreement."], "quote_scope": "abstract"}], "summary": "The Golden Retriever Lifetime Study is a prospective cohort of 3,044 US Golden Retrievers enrolled between 2012 and 2015 at 6 months to 2 years of age, followed for life with annual owner and veterinarian questionnaires, examinations and biobanked samples. Its primary outcomes are four cancers; secondary outcomes include other cancers and common age-related diseases. Questionnaire data are available to approved researchers under a data use agreement.", "notes": "A cancer-focused lifetime cohort rather than an aging study by design, but the only breed-wide lifetime cohort with biobanking in dogs; included as an aging cohort resource.", "parent_id": null, "tags": ["cohort", "golden-retriever", "cancer", "biobank", "lifetime"], "extracted_by": "claude-hand-curated"}
+{"id": "mct-fish-oil-carnitine-beagles-serum-aging-2012", "name": "Medium-chain triglyceride, fish oil and L-carnitine enriched foods against age-associated serum fatty acid and carnitine changes in healthy Beagles", "acronym": null, "kind": "randomized_controlled_trial", "status": "completed", "setting": "laboratory_colony", "intervention": "Foods enriched with medium-chain triglycerides (MCT), fish oil and L-carnitine (two treatment foods)", "intervention_class": "diet_or_supplement", "comparator": "Control food", "dose_regimen": "Treatment diets contained added L-carnitine (300 mg/kg) and 0.6% (treatment food 1) or 1.5% (treatment food 2) added fish oil; treatment food 2 also had increased MCT from coconut oil, added corn oil and reduced animal fat", "duration": "6 months", "population": {"n": 41, "n_note": "41 dogs randomized to 3 study groups; 3 removed during the study for unrelated reasons; age categories: mature adults (7 years and under) and geriatric adults (older than 7 years)", "breed": "Beagle", "age": "mean age 9.9 years (range 3.1 to 14.8)", "other": "healthy; equal numbers of females (n = 21; ovariohysterectomized) and males (n = 20; neutered)"}, "primary_outcome": "Serum fatty acid composition (gas chromatography) and serum carnitine metabolites (metabolomic profiling); body composition by dual energy x-ray absorptiometry", "result": "Serum concentrations of carnitine metabolites were decreased in geriatric (>7 years) vs. mature adult (<= 7 years) dogs, and supplementation with L-carnitine attenuated the effects of aging; serum eicosapentaenoic and docosahexaenoic FA increased in a dose-dependent manner; no change in total-lean-body weight, serum total protein or albumin by time or dietary treatment. The authors summarise that dietary MCT, fish oil, and L-carnitine counterbalanced the effects of aging on circulating concentrations of these compounds.", "lead_organization": "Hill's Pet Nutrition, Inc., Topeka, KS, USA", "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "23145181", "slug": null, "doi": "10.1371/journal.pone.0049510", "title": "Feeding healthy beagles medium-chain triglycerides, fish oil, and carnitine offsets age-related changes in serum fatty acids and carnitine metabolites.", "year": 2012, "role": "results", "quotes": ["The purpose of this study was to determine if feeding dogs medium-chain triglycerides (MCT), fish oil, and L-carnitine enriched foods offsets age-associated changes in serum fatty acids (FA) and carnitine metabolites.", "Forty-one healthy Beagles, mean age 9.9 years (range 3.1 to 14.8), were fed control or one of two treatment foods for 6 months.", "The treatment diets both contained added L-carnitine (300 mg/kg) and 0.6% (treatment food 1) or 1.5% (treatment food 2) added fish oil. Treatment food 2 also had increased MCT from coconut oil, added corn oil, and reduced animal fat.", "Composition of serum FA was determined by gas chromatography of FA methyl esters.", "Body composition was determined by dual energy x-ray absorptiometry.", "Among dog groups, there was no change in total-lean-body weight, or in serum total protein and serum albumin concentrations, based on time or dietary treatment.", "Serum concentrations of carnitine metabolites were decreased in geriatric (>7 years) vs. mature adult (≤ 7 years) dogs, and supplementation with L-carnitine attenuated the effects of aging.", "Serum concentrations of eicosapentaenoic and docosahexaenoic FA increased in a dose-dependent manner.", "In summary, dietary MCT, fish oil, and L-carnitine counterbalanced the effects of aging on circulating concentrations of these compounds."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "23145181", "slug": null, "doi": "10.1371/journal.pone.0049510", "title": "Feeding healthy beagles medium-chain triglycerides, fish oil, and carnitine offsets age-related changes in serum fatty acids and carnitine metabolites.", "year": 2012, "role": "design", "quotes": ["The study protocol was reviewed and approved by the Institutional Animal Care and Use Committee, Hill’s Pet Nutrition, Inc., Topeka, KS, USA (Permit Number: 09-487).", "Dogs were housed in pairs in indoor runs or in spacious rooms with natural light that varied with seasonal changes.", "Equal numbers of females (n = 21; ovariohysterectomized) and males (n = 20; neutered) were randomized to 3 study groups.", "Three animals were removed during the study for unrelated reasons: bladder carcinoma, surgery for intervertebral disc disease, and foot abscess with fever.", "To evaluate the influence of age, age categories were defined as 7 years and under (mature adults), or older than 7 years (geriatric adults).", "Three test foods were prepared by Hill’s Pet Nutrition, Inc."], "quote_scope": "fulltext"}], "summary": "Forty-one healthy Beagles (mean age 9.9 years, range 3.1 to 14.8) housed at a Hill's colony were randomized to a control food or one of two foods enriched with L-carnitine and fish oil, the second also containing medium-chain triglycerides, for 6 months. The stated purpose was to test whether these foods offset age-associated changes in serum fatty acids and carnitine metabolites. Carnitine metabolites were lower in geriatric than mature dogs and L-carnitine supplementation attenuated this, while serum EPA and DHA rose dose-dependently; the authors conclude the diet counterbalanced the effects of aging on these circulating compounds.", "notes": "No funding statement appears in the full text; the protocol was approved by Hill's IACUC and the foods were prepared by Hill's Pet Nutrition.", "parent_id": null, "tags": ["supplement", "diet", "fish-oil", "carnitine", "mct", "metabolomics", "colony"], "extracted_by": "claude-subagent-batch-C"}
+{"id": "astaxanthin-mitochondrial-function-beagles-2013", "name": "Dietary astaxanthin and age-associated mitochondrial dysfunction in young and geriatric Beagles", "acronym": null, "kind": "controlled_trial", "status": "completed", "setting": null, "intervention": "Astaxanthin fed daily", "intervention_class": "diet_or_supplement", "comparator": "0 mg astaxanthin", "dose_regimen": "0 or 20 mg astaxanthin daily for 16 wk", "duration": "16 wk (blood sampled wk 0, 8 and 16)", "population": {"n": 28, "n_note": "n=14 per age group (young and geriatric), fed 0 or 20 mg astaxanthin; group sizes per treatment within age group not stated", "breed": "Beagle", "age": "young (2.97±0.01 yr) and geriatric (10.71±0.01 yr)", "other": "healthy female"}, "primary_outcome": "Leukocyte mitochondrial function (membrane permeability, ATP production, cytochrome c oxidase/reductase, mitochondrial number) and plasma oxidative stress markers", "result": "Mitochondrial function improved in both young and geriatric dogs by increasing (P<0.05) ATP production, mitochondria mass, and cytochrome c oxidoreductase activity, especially in geriatric dogs compared with young dogs; astaxanthin also increased the reduced to oxidized glutathione ratio in young dogs and decreased nitric oxide in both age groups. Dietary astaxanthin improved mitochondrial function in blood leukocytes, most likely by alleviating oxidative damage to cellular DNA and protein.", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "23100599", "slug": null, "doi": "10.2527/jas.2012-5341", "title": "Astaxanthin modulates age-associated mitochondrial dysfunction in healthy dogs.", "year": 2013, "role": "results", "quotes": ["Young (2.97±0.01 yr; 8.16±0.15 kg BW) and geriatric (10.71±0.01 yr; 9.46±0.18 kg BW) healthy female Beagle dogs (n=14/age group) were fed 0 or 20 mg astaxanthin daily for 16 wk to examine modulation of mitochondrial function.", "Fasted blood was sampled on wk 0, 8, and 16.", "Mitochondria membrane permeability, ATP production, cytochrome c oxidase/reductase, and number were assessed in leukocytes whereas astaxanthin uptake, glutathione, superoxide dismutase, nitric oxide, 8-hydroxy-2'-deoxyguanosine, 8-isoprostane, and protein carbonyl were measured in plasma.", "Mitochondrial function improved in both young and geriatric dogs by increasing (P<0.05) ATP production, mitochondria mass, and cytochrome c oxidoreductase activity, especially in geriatric dogs compared with young dogs.", "Astaxanthin feeding also increased (P<0.05) the reduced glutathione to oxidized glutathione ratio in young dogs and decreased (P<0.05) nitric oxide in both young and geriatric dogs.", "Dietary astaxanthin improved mitochondrial function in blood leukocytes, most likely by alleviating oxidative damage to cellular DNA and protein."], "quote_scope": "abstract"}], "summary": "Healthy female Beagles in a young (about 3 years) and a geriatric (about 10.7 years) group, 14 per age group, were fed 0 or 20 mg astaxanthin daily for 16 weeks to examine modulation of age-associated mitochondrial dysfunction. Leukocyte mitochondrial function and plasma oxidative markers were measured at weeks 0, 8 and 16. Astaxanthin increased ATP production, mitochondrial mass and cytochrome c oxidoreductase activity, especially in geriatric dogs, and lowered nitric oxide in both age groups.", "notes": "The abstract does not describe randomization or blinding; the PubMed publication type for this record lists Randomized Controlled Trial. No full text available in the corpus; the total n of 28 is 14 per age group across two age groups.", "parent_id": null, "tags": ["supplement", "astaxanthin", "mitochondria", "oxidative-stress", "beagle"], "extracted_by": "claude-subagent-batch-C"}
+{"id": "mannac-place-learning-crossover-2014", "name": "N-acetyl-D-mannosamine (ManNAc) for age-related decline in place learning in dogs", "acronym": null, "kind": "crossover_trial", "status": "completed", "setting": null, "intervention": "N-acetyl-D-mannosamine (ManNAc), oral capsule", "intervention_class": "drug", "comparator": "Glucose capsule (control, equivalent calorie value)", "dose_regimen": "One capsule containing 250 mg ManNAc or glucose orally once a day for 2 months", "duration": "2-month courses of each treatment in a crossover design with a 1-month washout period", "population": {"n": 5, "n_note": "5 dogs with low cognitive levels (1 male, 4 females); statistical analyses on n=4 or 5", "breed": "Labrador Retriever", "age": "93.60 ± 11.98 months", "other": "Retired or demonstration dogs living at the Japan Guide Dog Association facility, in good health on medical examination"}, "primary_outcome": "Number of error trials in a place-learning test; active-resting cycle (daytime/nighttime motor activity ratio)", "result": "ManNAc treatment significantly reduced the number of error trials in the place-learning test, especially in the first month of administration. Three ManNAc-treated dogs also showed improvement in the active-resting cycle. In conclusion, ManNAc treatment appears to alleviate age-related cognitive dysfunction.", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "24430654", "slug": null, "doi": "10.1292/jvms.13-0351", "title": "N-acetyl-D-mannosamine treatment alleviates age-related decline in place-learning ability in dogs.", "year": 2014, "role": "results", "quotes": ["This study aimed to investigate the therapeutic effects of N-acetyl-D-mannosamine (ManNAc) on age-related cognitive dysfunction in dogs. ManNAc was administered to 5 dogs with low cognitive levels for 2 months, and the cognitive ability and active-resting cycle were periodically assessed for improvement.", "ManNAc treatment significantly reduced the number of error trials in the place-learning test, especially in the first month of administration. Three ManNAc-treated dogs also showed improvement in the active-resting cycle. In conclusion, ManNAc treatment appears to alleviate age-related cognitive dysfunction."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "24430654", "slug": null, "doi": "10.1292/jvms.13-0351", "title": "N-acetyl-D-mannosamine treatment alleviates age-related decline in place-learning ability in dogs.", "year": 2014, "role": "design", "quotes": ["The subjects were 5 Labrador Retrievers (1 male and 4 females, aged 93.60 ± 11.98 months;", "They were among the older dogs in the facility and, being retired or used only for\ndemonstrations, were able to remain in the facility throughout the experiment.", "All dogs underwent medical examination, including blood tests, and\nwere found to be in good health.", "The subjects of this study received 2-month courses of treatment with both ManNAc and glucose\n(control, an equivalent calorie value) in a crossover design with a 1-month washout period.\nOne capsule containing 250 mg ManNAc or glucose was administered orally to each subject once a\nday for 2 months.", "As the sample size was limited (n=4 or\n5), the level of statistical significance was set at 10%."], "quote_scope": "fulltext"}], "summary": "Five older Labrador Retrievers (93.60 ± 11.98 months) with low cognitive levels, living at a guide dog facility, received 2-month courses of 250 mg oral ManNAc and of glucose control in a crossover design with a 1-month washout. ManNAc significantly reduced place-learning error trials, especially in the first month, and three dogs improved in their active-resting cycle. Because the sample was 4 or 5 dogs, significance was set at 10%.", "notes": "Dogs were retired or demonstration dogs at the Japan Guide Dog Association facility, so setting is neither a laboratory colony nor client-owned and is left null. ManNAc is described by the authors as a therapeutic agent, so intervention_class is recorded as drug. Full-text quotes include the Markdown line breaks of the corpus file.", "parent_id": null, "tags": ["cognition", "mannac", "place-learning", "crossover", "labrador-retriever"], "extracted_by": "claude-subagent-batch-B"}
+{"id": "hills-functional-foods-renal-function-geriatric-colony-2016", "name": "Renal protective foods with functional food bioactives against age-associated decline in renal function (Hill's geriatric Beagle colony)", "acronym": null, "kind": "randomized_controlled_trial", "status": "completed", "setting": "laboratory_colony", "intervention": "Control renal protective food supplemented with increasing amounts of functional food bioactives (fish oil, lipoic acid, fruits and vegetables, higher quality protein sources): functional foods FF1 and FF2", "intervention_class": "diet_or_supplement", "comparator": "Traditional renal protective food (control; energy dense and mildly protein-restricted; Hill's Science Diet Mature Adult)", "dose_regimen": "Both functional foods contained 0.5% fish oil and 100 mg/kg lipoic acid; FF1 contained 2.75% fruits and vegetables, 7% egg protein and 7.5% wet meat chicken; FF2 contained 7.5% fruits and vegetables, 14% egg protein, 10% wet meat chicken and 955 IU/kg a-tocopherol acetate", "duration": "6 months", "population": {"n": 111, "n_note": "81 geriatric dogs randomly assigned to three foods (n = 27 per group) after blocking for sex, plus 30 mature-adult dogs as a cross-sectional comparison group", "breed": "Beagle", "age": "geriatric: mean age 10.4, range 7.9-14.2 years; mature adult: mean age 5.0, range 3.3-6.9 years", "other": "healthy colony dogs; 35 ovariohysterectomized females, 44 neutered males and 2 intact males among the geriatric dogs"}, "primary_outcome": "Glomerular filtration rate (GFR), lean body percent (LB%) by dual energy x-ray absorptiometry, and circulating biomarkers and metabolites including symmetric dimethylarginine (SDMA)", "result": "Geriatric dogs consuming all three foods increased (P<0.001) GFR over time; group averages ranged from 13.0-16.9%. Dogs fed the highest supplemented level of bioactives (FF2) had lower (P<0.001) SDMA concentrations (-14.3%). Feeding functional foods did not alter body weight, but increased (P<0.001) serum protein concentration (+6.7%). The authors conclude that supplementation with functional food bioactives can temporarily reverse the age-associated decline in renal function and serum total protein.", "lead_organization": "Pet Nutrition Center, Hill's Pet Nutrition, Inc., Topeka, KS", "sponsor_or_funder": "Hill's Pet Nutrition, Inc.", "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "27925141", "slug": null, "doi": "10.1007/s12603-015-0636-3", "title": "Nutritional Interventions that Slow the Age-Associated Decline in Renal Function in a Canine Geriatric Model for Elderly Humans.", "year": 2016, "role": "results", "quotes": ["To determine the effects of feeding traditional and renal protective foods (RPF) supplemented with functional food bioactives on glomerular filtration rate (GFR), lean body percent (LB%), and selected circulating biomarker and metabolite concentrations in a geriatric dog model.", "Randomized block design and cross-sectional study.", "Hill's Pet Nutrition, Inc. dog colony.", "Eighty-one geriatric dogs (mean age, 10.4; range, 7.9-14.2 years) and 30 mature-adult dogs (mean age, 5.0; range, 3.3-6.9 years).", "Geriatric dogs were fed one of three foods (n = 27 per group) for 6 months: a traditional RPF (control) that was energy dense and mildly protein-restricted, or control food supplemented with increasing amounts of functional food bioactives: fish oil, lipoic acid, fruits and vegetables, and higher quality protein sources [functional foods one (FF1) and two (FF2)].", "Renal function was assessed by GFR, LB% was determined by dual energy x-ray absorptiometry, and circulating biomarkers and metabolites were measured in blood.", "Geriatric dogs consuming all three foods increased (P<0.001) GFR over time; group averages ranged from 13.0-16.9%.", "Dogs fed the highest supplemented level of bioactives (FF2) had lower (P<0.001) symmetric dimethylarginine (SDMA) concentrations (-14.3%).", "Feeding functional foods did not alter body weight, but increased (P<0.001) serum protein concentration (+6.7%).", "Supplementation with functional food bioactives can temporarily reverse the age-associated decline in renal function and serum total protein."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "27925141", "slug": null, "doi": "10.1007/s12603-015-0636-3", "title": "Nutritional Interventions that Slow the Age-Associated Decline in Renal Function in a Canine Geriatric Model for Elderly Humans.", "year": 2016, "role": "design", "quotes": ["The study protocol was reviewed and approved by the Institutional Animal Care and Use Committee, Hill's Pet Nutrition, Inc., Topeka, KS, USA (Permit Number: CP354).", "This was a feeding trial involving 81 healthy, geriatric Beagle dogs (35 ovariohysterectomized females, 44 neutered males, and 2 intact males) with mean age of 10.4 years (range: 7.9 to 14.2 years) and mean initial BW of 14.1 kg (range: 9.0 to 18.1 kg).", "After blocking for sex, dogs were randomly assigned to one of three food groups (n=27 each; control, FF1, and FF2; Table 1).", "The control food was Hill's Science Diet Mature Adult, Hill's Pet Nutrition, Inc.", "The two functional foods were designed to increase the healthy lifespan of aging dogs.", "Both functional foods contained 0.5% fish oil, and 100 mg/kg lipoic acid.", "FF1 contained unique protein sources compared with control food in that egg protein (7%), corn gluten meal (6.4%), and wet meat chicken (7.5%) replaced other carbohydrate and protein sources in control food.", "FF2 differed from control and FF1 in that it contained additional amounts of fruits and vegetables; i.e. beet pulp, citrus pulp, carrot granules, dried spinach, and tomato pomace (each present at 1.50% of formula; total 7.5%), more a-tocopherol acetate (955 IU/kg, as fed; Table 1), and increased egg protein (14%) and wet meat chicken (10%), but no corn gluten meal.", "Funded by and performed at the Pet Nutrition Center, Hill's Pet Nutrition, Inc., Topeka, KS."], "quote_scope": "fulltext"}], "summary": "Eighty-one healthy geriatric Beagles (mean 10.4 years) at the Hill's Pet Nutrition colony were randomly assigned, after blocking for sex, to a control renal protective food or to one of two functional foods (FF1, FF2) with increasing amounts of fish oil, lipoic acid, fruits and vegetables and higher quality protein, for 6 months; 30 mature adult dogs served as a cross-sectional comparison. GFR, lean body percent and circulating biomarkers were measured. GFR increased over time in all three geriatric groups, FF2 lowered SDMA by 14.3%, and serum protein rose; the authors conclude functional food bioactives can temporarily reverse the age-associated decline in renal function.", "notes": "Separate from the client-owned test-food study (PMID 27088214), which used different dogs, setting and comparator.", "parent_id": null, "tags": ["diet", "supplement", "renal", "sdma", "gfr", "fish-oil", "lipoic-acid", "colony"], "extracted_by": "claude-subagent-batch-C"}
+{"id": "hills-test-food-sdma-client-owned-geriatric-dogs-2016", "name": "Test food designed to promote healthy aging vs owner's-choice foods on serum SDMA and creatinine in client-owned geriatric dogs", "acronym": null, "kind": "randomized_controlled_trial", "status": "completed", "setting": "client_owned", "intervention": "Test food (renal protective food) containing functional lipids (fish oil), antioxidants (lipoic acid, vitamins C and E), L-carnitine, botanicals (fruits and vegetables), controlled sodium concentration and high quality protein sources", "intervention_class": "diet_or_supplement", "comparator": "Owner's-choice foods (non-nutritionally controlled cohort)", "dose_regimen": null, "duration": "6 months (biomarkers evaluated at baseline, 3 and 6 months)", "population": {"n": 210, "n_note": "210 dogs reported in the abstract; 255 dogs enrolled per the full text (small: 26 test food / 25 owner's-choice; medium: 25 / 24; large: 78 / 77)", "breed": null, "age": "small (6.8 to 11.4 kg) and medium dogs (11.5 to 22.7 kg) were >= 9 years, dogs >22.7 kg were >= 7 years at baseline; enrolled dogs had mean age 9.7 years (range 7 to 15 years)", "other": "client-owned geriatric dogs with serum creatinine within the reference interval and free of chronic disease at baseline; recruited through seventeen veterinary clinics around the United States"}, "primary_outcome": "Serum symmetric dimethylarginine (SDMA) and creatinine (Cr) concentrations, plus urinalysis, at baseline, 3 and 6 months", "result": "Only dogs consuming test food showed significant decreases in serum SDMA and Cr concentrations (both P <= 0.05) across time. Among 18 dogs with increased SDMA but normal Cr (consistent with IRIS Stage 1 CKD), the decreases in serum SDMA and Cr were significant (both P = 0.03) only for dogs fed test food.", "lead_organization": "Hill's Pet Nutrition, Inc., Topeka, KS (protocol approval and test food); contract research organization with seventeen US veterinary clinics", "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "27088214", "slug": null, "doi": "10.1371/journal.pone.0153653", "title": "Positive Impact of Nutritional Interventions on Serum Symmetric Dimethylarginine and Creatinine Concentrations in Client-Owned Geriatric Dogs.", "year": 2016, "role": "results", "quotes": ["A prospective study was conducted in client-owned geriatric dogs to evaluate the short-term effects of a test food on serum symmetric dimethylarginine (SDMA) and creatinine (Cr) concentrations.", "Test food contained functional lipids (fish oil), antioxidants (lipoic acid, vitamins C and E), L-carnitine, botanicals (fruits and vegetables), controlled sodium concentration, and high quality protein sources (high bioavailability and an ideal amino acid composition).", "Dogs (n = 210) were fed either test food or owner's-choice foods (non-nutritionally controlled cohort).", "Dogs were included based on age and body weight: small (6.8 to 11.4 kg) and medium dogs (11.5 to 22.7 kg) were ≥ 9 years, whereas dogs >22.7 kg were ≥ 7 years at baseline.", "At baseline, all dogs had to have serum Cr concentrations within the reference interval and be free of chronic disease.", "Renal function biomarkers and urinalysis results at baseline, and after consuming test food or owner's-choice foods for 3 and 6 months, were evaluated.", "Only dogs consuming test food showed significant decreases in serum SDMA and Cr concentrations (both P ≤ 0.05) across time.", "At baseline or during the 6-month feeding trial, 18 dogs (8.6%) had increased serum SDMA, but normal serum Cr, consistent with IRIS Stage 1 chronic kidney disease.", "The decreases in serum SDMA and Cr concentrations were significant (both P = 0.03) only for dogs fed test food.", "These results suggest that nonazotemic dogs with elevated serum SDMA (early renal insufficiency) when fed a test food designed to promote healthy aging are more likely to demonstrate improved renal function compared with dogs fed owner's-choice foods."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "27088214", "slug": null, "doi": "10.1371/journal.pone.0153653", "title": "Positive Impact of Nutritional Interventions on Serum Symmetric Dimethylarginine and Creatinine Concentrations in Client-Owned Geriatric Dogs.", "year": 2016, "role": "design", "quotes": ["This study protocol was reviewed and approved by the Institutional Animal Care and Use Committee, Hill’s Pet Nutrition, Inc., Topeka, KS, USA (Permit Number: CP-522).", "This was a prospective feeding study of 6-months duration. A contract research organization recruited seventeen veterinary clinics from around the United States.", "Once dogs were accepted into the study, they were randomized to receive either test food or owner’s-choice foods.", "The veterinarians and the owners were blinded as to the sponsor of the study.", "There were a total of 255 dogs enrolled in the study; mean age of 9.7 years (range 7 to 15 years).", "Of the dogs classified as small (6.8–11.4 kg), there were 26 fed test food and 25 fed owner’s-choice foods. Of the dogs classified as medium (11.5–22.7 kg), there were 25 fed test food and 24 fed owner’s-choice foods. Of the dogs classified as large (>22.7 kg), there were 78 fed test food and 77 fed owner’s-choice foods.", "The test food was produced by Hill’s Pet Nutrition, Inc., Topeka, KS, and met the nutritional requirements for adult dogs (≥ 1 year) as established by the Association of American Feed Control Officials (AAFCO)."], "quote_scope": "fulltext"}], "summary": "A prospective 6-month feeding study in client-owned geriatric dogs recruited through seventeen US veterinary clinics randomized dogs to a Hill's test food designed to promote healthy aging (fish oil, lipoic acid, vitamins C and E, L-carnitine, fruits and vegetables, controlled sodium, high quality protein) or to owner's-choice foods; 255 dogs were enrolled and 210 are reported in the abstract. Serum SDMA and creatinine were measured at baseline, 3 and 6 months. Only dogs fed the test food showed significant decreases in SDMA and creatinine across time, including among the 18 dogs with elevated SDMA consistent with IRIS Stage 1 CKD.", "notes": "The sponsor is not named in the text (veterinarians and owners were blinded as to the sponsor); the protocol was approved by Hill's IACUC and the test food was produced by Hill's. Separate from the Hill's colony functional-food study (PMID 27925141).", "parent_id": null, "tags": ["diet", "supplement", "renal", "sdma", "creatinine", "client-owned"], "extracted_by": "claude-subagent-batch-C"}
+{"id": "beagle-abeta-vaccination-behavioral-enrichment", "name": "Aβ vaccination combined with behavioral enrichment in aged beagles", "acronym": null, "kind": "controlled_trial", "status": "completed", "setting": "laboratory_colony", "intervention": "Active vaccine against fibrillar Aβ 1-42 (VAC) and behavioral enrichment (ENR), alone and combined", "intervention_class": "combination", "comparator": "Control/control group: alum-only injections without behavioral enrichment", "dose_regimen": "0.5 mg fibrillar Aβ with 2% aluminum hydroxide (alum) injected subcutaneously, boosted after 2 weeks and then monthly; control animals received alum injections. Enrichment: two 20-min outdoor group walks weekly, weekly rotation of play toys, and cognitive enrichment tasks", "duration": "20 months", "population": {"n": 34, "n_note": "34 beagles at study start; groups C/C n=8, C/V n=8, E/C n=8, E/V n=10", "breed": "Beagle", "age": "11-12 years (abstract); 10.5-13.6 years at study start (full text)", "other": "31 dogs from Lovelace Respiratory Research Institute and 3 from Harlan; housed in pairs (n=12) or singly (n=22) in kennels with indoor/outdoor runs"}, "primary_outcome": "Cognition (learning and memory), brain Aβ and pyroglutamate Aβ, cerebrospinal fluid Aβ42, brain-derived neurotrophic factor mRNA, and microhemorrhages", "result": "VAC decreased brain Aβ, pyroglutamate Aβ, increased cerebrospinal fluid Aβ 42 and brain-derived neurotrophic factor RNA levels but also increased microhemorrhages. ENR reduced brain Aβ and prevented microhemorrhages. The combination treatment resulted in a significant maintenance of learning over time, reduced Aβ, and increased brain-derived neurotrophic factor mRNA despite increased microhemorrhages; however, there were no benefits to memory.", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "27776266", "slug": null, "doi": "10.1016/j.neurobiolaging.2016.09.007", "title": "Aβ vaccination in combination with behavioral enrichment in aged beagles: effects on cognition, Aβ, and microhemorrhages.", "year": 2017, "role": "results", "quotes": ["An active vaccine against fibrillar Aβ 1-42 (VAC) in aged beagles resulted in maintenance but not improvement of cognition along with reduced brain Aβ.", "Aged dogs (11-12 years) were placed into 4 groups: (1) control/control (C/C); (2) control/VAC (C/V); (3) ENR/control (E/C); and (4) ENR/VAC (E/V) and treated for 20 months.", "VAC decreased brain Aβ, pyroglutamate Aβ, increased cerebrospinal fluid Aβ 42 and brain-derived neurotrophic factor RNA levels but also increased microhemorrhages. ENR reduced brain Aβ and prevented microhemorrhages.", "The combination treatment resulted in a significant maintenance of learning over time, reduced Aβ, and increased brain-derived neurotrophic factor mRNA despite increased microhemorrhages; however, there were no benefits to memory."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "27776266", "slug": null, "doi": "10.1016/j.neurobiolaging.2016.09.007", "title": "Aβ vaccination in combination with behavioral enrichment in aged beagles: effects on cognition, Aβ, and microhemorrhages.", "year": 2017, "role": "design", "quotes": ["the longitudinal study started with 34 beagles (10.5 – 13.6 years – Table 1): 31 from Lovelace Respiratory Research Institute (LRRI – Albuquerque, NM) and 3 from Harlan (Riglan Farms, Inc, Mount Horeb, Wisconsin).", "Dogs were housed in pairs (n=12) or singly (n=22) in kennel buildings with indoor/outdoor runs measuring 91 cm x 600 cm", "each dog received 0.5 mg of fibrillar Aβ (500 μl) that was added to 50 μl of 2% aluminum hydroxide (alum) suspension (Accurate Chemical, Westbury, NY) and 450 μl of PBS and vortexed. All animals that did not receive fibrillar Aβ 1–42 were given alum injections. Animals were immunized subcutaneously in the back of the neck and monitored for adverse reactions. After 2 weeks, animals were boosted with an additional injection followed by monthly injections thereafter.", "Dogs in the behavioral enrichment group were given two 20-min walks outdoors in groups of 3–4 animals each week. Play toys were rotated through their kennels on a weekly basis.", "Animals were assigned to one of four treatment groups balancing for baseline cognitive test scores, sex, and age. All control animals received alum only as the injection while those receiving the active vaccine were injected with fibrillar Aβ1–42 mixed with alum. These groups included 1) control/control (n=8; C/C); (2) control/vaccine (n=8; C/V); (3) behavioral enrichment/control (n=8; E/C); (4) behavioral enrichment and vaccine (n=10; E/V)."], "quote_scope": "fulltext"}], "summary": "Thirty-four aged beagles (11-12 years) were assigned, balancing baseline cognitive scores, sex and age, to control, active fibrillar Aβ 1-42 vaccine, behavioral enrichment, or vaccine plus enrichment groups and treated for 20 months. The vaccine (0.5 mg fibrillar Aβ with alum, subcutaneous, boosted at 2 weeks then monthly) reduced brain Aβ and raised CSF Aβ42 and BDNF RNA but increased microhemorrhages, while enrichment reduced brain Aβ and prevented microhemorrhages. The combination produced significant maintenance of learning over time with reduced Aβ and increased BDNF mRNA, but no benefit to memory.", "notes": "Groups were assigned by balancing for baseline cognitive test scores, sex and age rather than by stated randomization, so kind is recorded as controlled_trial. Dogs were housed, and procedures approved, at Lovelace Respiratory Research Institute; the full text has no funding statement. Separate from the earlier antioxidant/enrichment longitudinal study, whose kennels and cognitive protocols it reused.", "parent_id": null, "tags": ["cognition", "vaccine", "amyloid", "enrichment", "beagle", "brain-aging"], "extracted_by": "claude-subagent-batch-B"}
+{"id": "labrador-inflammaging-cohort-2018", "name": "Longitudinal analysis of inflammation, immune function and oxidative stress markers in 80 Labrador retrievers from adulthood to end of life", "acronym": null, "kind": "longitudinal_cohort", "status": "completed", "setting": null, "intervention": null, "intervention_class": "none", "comparator": null, "dose_regimen": null, "duration": "From adulthood to the end of life", "population": {"n": 80, "n_note": "80 Labrador retrievers followed from adulthood to the end of life", "breed": "Labrador retriever", "age": "From adulthood to the end of life", "other": null}, "primary_outcome": "Changes with age in markers of inflammation (immunoglobulin M, immunoglobulin G, C-reactive protein), oxidative stress (8-hydroxy-2-deoxyguanosine) and the heat shock protein 70 response to heat stress", "result": "Serum levels of immunoglobulin M (p < .001) and 8-hydroxy-2-deoxyguanosine (p < .001) increased with age, whereas no effect of age was detected for immunoglobulin G or C-reactive protein unless the last year of life was included in the analysis (p = .002). Baseline levels of heat shock protein 70 decreased with age (p < .001) while those after exposure to heat stress were maintained (p = .018); when excluding final year of life data, a decline in the heat shock protein 70 response after heat stress was observed (p = .004).", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "29126143", "slug": null, "doi": "10.1093/gerona/glx182", "title": "Understanding How Dogs Age: Longitudinal Analysis of Markers of Inflammation, Immune Function, and Oxidative Stress.", "year": 2018, "role": "results", "quotes": ["Detrimental physiological changes occurring later in life must be understood before interventions can be made to slow or reduce them.", "To determine whether similar processes occur in the aging dog, changes in markers of inflammation and oxidative stress were investigated in 80 Labrador retrievers from adulthood to the end of life.", "Serum levels of immunoglobulin M (p < .001) and 8-hydroxy-2-deoxyguanosine (p < .001) increased with age, whereas no effect of age was detected for immunoglobulin G or C-reactive protein unless the last year of life was included in the analysis (p = .002).", "Baseline levels of heat shock protein 70 decreased with age (p < .001) while those after exposure to heat stress were maintained (p = .018).", "However, when excluding final year of life data, a decline in the heat shock protein 70 response after heat stress was observed (p = .004).", "These findings indicate that aging dogs undergo changes similar to human inflammaging and offer the possibility of nutritional or pharmacological intervention to delay or reduce these effects."], "quote_scope": "abstract"}], "summary": "Markers of inflammation, immune function and oxidative stress were measured longitudinally in 80 Labrador retrievers from adulthood to the end of life to determine whether dogs undergo inflammaging-like changes. Serum immunoglobulin M and 8-hydroxy-2-deoxyguanosine increased with age, immunoglobulin G and C-reactive protein changed only when the last year of life was included, and baseline heat shock protein 70 declined with age. The authors conclude that aging dogs undergo changes similar to human inflammaging, opening the possibility of nutritional or pharmacological intervention.", "notes": "Observational longitudinal study with no intervention; PubMed lists the publication type 'Clinical Trial, Veterinary' but the abstract describes no treatment. The abstract does not state the housing setting, the funder or the calendar years.", "parent_id": null, "tags": ["cohort", "inflammaging", "oxidative-stress", "immune-function", "labrador-retriever", "biomarkers"], "extracted_by": "claude-subagent-batch-A"}
+{"id": "antioxidant-omega3-enriched-diet-telomere-mobility-shepherd-dogs-2020", "name": "Diet enriched with antioxidants, mitochondrial cofactors and omega-3 fatty acids on telomere length and joint mobility in young and old shepherd dogs", "acronym": null, "kind": "randomized_controlled_trial", "status": "completed", "setting": null, "intervention": "Diet enriched with antioxidants, mitochondrial cofactors and omega-3 fatty acids", "intervention_class": "diet_or_supplement", "comparator": "Control diet", "dose_regimen": null, "duration": "6 months (measurements at the outset, after 3 and after 6 months)", "population": {"n": 74, "n_note": "36 young and 38 old shepherd dogs", "breed": "shepherd dogs", "age": "young and old (ages not stated in the abstract)", "other": null}, "primary_outcome": "Mean and minimum telomere lengths; minimum and maximum joint angles and range of motion of the shoulder, elbow, carpal, hip, stifle and tarsal joints by computer-assisted gait analysis", "result": "A positive influence of the enriched diet on old dogs could be verified for minimum telomere length and all three parameters of the shoulder joint on the side with the higher vertical ground reaction force after 6 months. In the other joints there were less significant differences; in some cases they indicated a contrary influence of the enriched diet on young dogs, probably due to its reduced protein content.", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "32000015", "slug": null, "doi": "10.1016/j.rvsc.2020.01.008", "title": "Effect of antioxidants, mitochondrial cofactors and omega-3 fatty acids on telomere length and kinematic joint mobility in young and old shepherd dogs - A randomized, blinded and placebo-controlled study.", "year": 2020, "role": "results", "quotes": ["In dogs, decreasing telomere length is a biomarker for cellular aging.", "As aging is thought to be related to oxidative stress, it may be counteracted by a diet enriched with antioxidants, mitochondrial cofactors and omega-3 fatty acids.", "This randomized, blinded and placebo-controlled study examined the influence of an accordingly enriched diet compared to a control diet on 36 young and 38 old shepherd dogs.", "At the outset, after 3 and after 6 months, mean and minimum telomere lengths were measured.", "Furthermore, minimum and maximum joint angles and range of motion of the shoulder, elbow, carpal, hip, stifle and tarsal joints were measured by computer-assisted gait analysis.", "A positive influence of the enriched diet on old dogs could be verified for minimum telomere length and all three parameters of the shoulder joint on the side with the higher vertical ground reaction force after 6 months.", "In the other joints there were less significant differences; in some cases they indicated a contrary influence of the enriched diet on young dogs, probably due to its reduced protein content.", "For elderly dogs it is advisable to feed these nutritional supplements."], "quote_scope": "abstract"}], "summary": "A randomized, blinded, placebo-controlled study fed 36 young and 38 old shepherd dogs either a diet enriched with antioxidants, mitochondrial cofactors and omega-3 fatty acids or a control diet, on the premise that aging-related oxidative stress could be counteracted by such a diet. Telomere length and joint kinematics from computer-assisted gait analysis were measured at the outset and after 3 and 6 months. In old dogs the enriched diet had a positive effect on minimum telomere length and on shoulder joint mobility after 6 months, with smaller or contrary effects in other joints and in young dogs.", "notes": "No full text in the corpus; exact ages, diet composition and setting are not stated in the abstract. The total n of 74 is the sum of 36 young and 38 old dogs.", "parent_id": null, "tags": ["diet", "supplement", "antioxidant", "omega-3", "telomere", "mobility", "gait"], "extracted_by": "claude-subagent-batch-C"}
+{"id": "triad-rapamycin", "name": "Test of Rapamycin in Aging Dogs (TRIAD)", "acronym": "TRIAD", "kind": "randomized_controlled_trial", "status": "ongoing", "setting": "client_owned", "intervention": "Rapamycin (weekly low-dose)", "intervention_class": "drug", "comparator": "placebo", "dose_regimen": "Weekly low-dose rapamycin; the rapamycin treatment group receives a cumulative dose of 0.15 mg/kg administered once weekly (as described in the 2023 Texas A&M trial report)", "duration": "One-year course of weekly rapamycin; lifespan and healthspan endpoints", "population": {"n": null, "n_note": null, "breed": null, "age": "Healthy, middle-aged dogs", "other": "Large-breed dogs recruited from Dog Aging Project participants; privately owned; seen every six months at one of seven US veterinary teaching hospitals"}, "primary_outcome": "Lifespan, plus healthspan metrics (heart and cognitive function, age-related disease incidence)", "result": null, "lead_organization": "Dog Aging Project (multicenter; seven US veterinary teaching hospitals)", "sponsor_or_funder": null, "registration": [], "start_year": 2021, "end_year": null, "sources": [{"type": "pmid", "pmid": "39951177", "slug": null, "doi": "10.1007/s11357-024-01484-7", "title": "Test of Rapamycin in Aging Dogs (TRIAD): study design and rationale for a prospective, parallel-group, double-masked, randomized, placebo-controlled, multicenter trial of rapamycin in healthy middle-aged dogs from the Dog Aging Project.", "year": 2025, "role": "design", "quotes": ["The Test of Rapamycin In Aging Dogs (TRIAD) randomized clinical trial is a parallel-group, double-masked, randomized, placebo-controlled, multicenter trial that will test the ability of rapamycin to prolong lifespan and improve several healthspan metrics in healthy, middle-aged dogs recruited from Dog Aging Project participants.", "Here, we describe the rationale, design, and goals of the TRIAD randomized clinical trial, the first rigorous test of a pharmacologic intervention against biological aging with lifespan and healthspan metrics as endpoints to be performed outside of the laboratory in any species."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "35110758", "slug": null, "doi": "10.1038/s41586-021-04282-9", "title": "An open science study of ageing in companion dogs.", "year": 2022, "role": "design", "quotes": ["carrying out a randomized, double-masked, placebo-controlled study to determine the effects of rapamycin on lifespan and healthspan in large-breed, middle-aged dogs", "We will test the hypothesis that a one-year course of weekly low-dose rapamycin can increase lifespan, improve heart and cognitive function, and reduce age-related disease incidence in middle-aged, large-breed dogs. Enrolment into TRIAD began in June 2021 and will continue through 2022.", "Owners of TRIAD dogs bring their dogs to one of seven US veterinary teaching hospitals every six months, where the samples are collected and the dog’s cardiac health and function are also assessed.", "a National Institute on Aging-constituted data and safety monitoring board oversees the TRIAD trial", "As this is a community science project and all study subjects are privately owned dogs"], "quote_scope": "fulltext"}, {"type": "pmid", "pmid": "37275618", "slug": null, "doi": "10.3389/fvets.2023.1168711", "title": "A masked, placebo-controlled, randomized clinical trial evaluating safety and the effect on cardiac function of low-dose rapamycin in 17 healthy client-owned dogs.", "year": 2023, "role": "design", "quotes": ["our group is conducting a larger masked, placebo-controlled, randomized clinical trial (the Test of Rapamycin in Aging Dogs) in which the rapamycin treatment group will receive a higher cumulative dose (0.15 mg/kg) administered once weekly"], "quote_scope": "fulltext"}], "summary": "TRIAD is a parallel-group, double-masked, randomized, placebo-controlled, multicenter trial that will test whether rapamycin prolongs lifespan and improves healthspan metrics in healthy, middle-aged, large-breed dogs recruited from Dog Aging Project participants. The hypothesis is that a one-year course of weekly low-dose rapamycin (0.15 mg/kg once weekly) can increase lifespan, improve heart and cognitive function and reduce age-related disease incidence. Enrolment began in June 2021, dogs are seen every six months at one of seven US veterinary teaching hospitals, and no results have been reported.", "notes": "Design paper only; no results reported. A National Institute on Aging-constituted data and safety monitoring board oversees the trial; the funder is not stated in the abstracts (the Dog Aging Project is supported by NIA U19 AG057377 per the 2023 Texas A&M paper's funding statement). The once-weekly 0.15 mg/kg dose and the June 2021 enrolment start come from the 2023 Texas A&M paper and the 2022 Nature design paper respectively, not from the TRIAD design abstract. No registry id is given in these sources.", "parent_id": null, "tags": ["rapamycin", "lifespan", "healthspan", "dog-aging-project", "multicenter", "ongoing"], "extracted_by": "claude-subagent-batch-A"}
+{"id": "ashwagandha-geriatric-labradors-rct-2024", "name": "Ashwagandha (Withania somnifera) root extract on aging-related changes in healthy geriatric client-owned dogs", "acronym": null, "kind": "randomized_controlled_trial", "status": "completed", "setting": "client_owned", "intervention": "Withania somnifera/ashwagandha root extract (ARE)", "intervention_class": "diet_or_supplement", "comparator": "Placebo control", "dose_regimen": "15 mg/kg, once daily, orally", "duration": "60 days (assessed at initiation, day 30 and day 60); conducted July 2022 to September 2022", "population": {"n": 20, "n_note": "10 dogs in the ARE group and 10 in the placebo group (1:1 randomization)", "breed": "Labrador", "age": "aged 8 years or older", "other": "apparently healthy, obese, client-owned geriatric dogs recruited at a pet clinic in Telangana, India"}, "primary_outcome": "Serum cortisol, haematological profile, biochemical markers (liver and kidney function), antioxidant indicators and anti-inflammatory responses", "result": "Erythrocyte count and haemoglobin were significantly increased with ARE (p < 0.001) and leukocyte count decreased (p < 0.05); liver function markers (ALT, AST, albumin, globulin; p < 0.001 at day 60) and kidney function markers (creatinine, BUN; p < 0.001 at days 30 and 60) decreased in ARE-treated dogs compared to placebo; oxidative stress markers were significantly modulated; serum cortisol reduced significantly (p < 0.001); and key inflammatory markers (IFN-gamma, TNF-alpha, NF-kB, IL-10) decreased from baseline (p < 0.001) at day 60. The authors conclude ARE has adaptogenic properties in healthy geriatric dogs.", "lead_organization": "College of Veterinary Science, P.V.N.R. Telangana Veterinary University, Hyderabad (ethics approval); conducted at Cure Pet Clinic, Hanamkonda, Telangana, India", "sponsor_or_funder": "None stated (funding information: None)", "registration": [], "start_year": 2022, "end_year": 2022, "sources": [{"type": "pmid", "pmid": "39078383", "slug": null, "doi": "10.1002/vms3.1556", "title": "Effects of ashwagandha (Withania somnifera) root extract on aging-related changes in healthy geriatric dogs: A randomized, double-blinded placebo-controlled study.", "year": 2024, "role": "results", "quotes": ["This study aimed to explore the clinical potential of Withania somnifera/ashwagandha root extract (ARE) to mitigate age-related changes in healthy geriatric dogs.", "A randomized, double-blind, placebo-controlled trial was conducted in Telangana, India, from July 2022 to September 2022. Twenty apparently healthy dogs, aged 8 years or older, were enrolled.", "The dogs were divided into two groups to receive ARE (15 mg/kg, once daily, orally) or a placebo control.", "Various parameters, including serum cortisol levels, haematological profiles, biochemical markers, antioxidant indicators and anti-inflammatory responses, were assessed at the initiation of study, day 30, and day 60.", "The erythrocyte count and haemoglobin levels were significantly increased with ARE (p < 0.001), whereas leukocyte count decreased (p < 0.05).", "Moreover, significant decreases in important markers of liver function (alanine aminotransferase, aspartate aminotransferase, albumin and globulin; p < 0.001 at day 60), as well as kidney function markers (creatinine and blood urea nitrogen; p < 0.001 at days 30 and 60), were observed in ARE-treated dogs compared to the placebo control group.", "In addition, the levels of markers of oxidative stress (superoxide dismutase, catalase, glutathione and malondialdehyde) were significantly modulated by ARE intervention, indicating strong antioxidant effects.", "Interestingly, serum cortisol levels reduced significantly with ARE (p < 0.001).", "Compared to baseline, ARE significantly decreased key inflammatory markers, including interferon-γ, tumour necrosis factor-α, nuclear factor kappa light chain enhancer of activated B cells and interleukin-10 (p < 0.001) levels at day 60.", "In conclusion, the findings of this study suggest that ARE has adaptogenic properties in healthy geriatric dogs by improving haematological and biochemical profiles, enhancing antioxidant defence, reducing stress and modulating inflammatory responses."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "39078383", "slug": null, "doi": "10.1002/vms3.1556", "title": "Effects of ashwagandha (Withania somnifera) root extract on aging-related changes in healthy geriatric dogs: A randomized, double-blinded placebo-controlled study.", "year": 2024, "role": "design", "quotes": ["A total of 20 visibly healthy, obese geriatric Labrador dogs aged ≥8 years with normal haemato‐biochemical parameters were enrolled, irrespective of their gender.", "All the dogs enrolled were client‐owned, living in Telangana, India, and were recruited at the Pet clinic during routine visits.", "Thus, 10 dogs were in the ARE group, and another 10 dogs were in the placebo group (Figure 1).", "The study protocol was approved by the Institutional Animal Ethics Committee (IAEC) at the College of Veterinary Science, P.V.N.R. Telangana Veterinary University, Hyderabad (29/25/C.V.Sc, Hyderabad, dated 2/7/2022)", "The randomized, double‐blind, placebo‐controlled trial was conducted from July 2022 to September 2022 at Cure Pet Clinic, Hanamkonda, Telangana, India.", "## FUNDING INFORMATION\n\nNone."], "quote_scope": "fulltext"}], "summary": "A randomized, double-blind, placebo-controlled trial at a pet clinic in Telangana, India (July to September 2022) enrolled 20 apparently healthy, obese, client-owned geriatric Labradors aged 8 years or older and gave 10 of them ashwagandha root extract at 15 mg/kg orally once daily and 10 a placebo, to test whether ARE mitigates age-related changes. Haematology, liver and kidney markers, oxidative stress, cortisol and inflammatory markers were measured at baseline, day 30 and day 60. ARE raised erythrocyte count and haemoglobin, lowered liver and kidney markers relative to placebo, reduced cortisol and lowered inflammatory cytokines from baseline at day 60.", "notes": "Separate trial from the ashwagandha gut-parameter study in research Beagles (PMID 39911483): different animals, setting and ethics approval.", "parent_id": null, "tags": ["supplement", "ashwagandha", "adaptogen", "inflammation", "oxidative-stress", "cortisol"], "extracted_by": "claude-subagent-batch-C"}
+{"id": "fortetropin-senior-dogs-mobility-rct-2022", "name": "Fortetropin in geriatric and senior dogs with reduced mobility", "acronym": null, "kind": "randomized_controlled_trial", "status": "completed", "setting": null, "intervention": "Fortetropin, a nonthermal-pasteurized, freeze-dried, fertilized egg yolk product", "intervention_class": "diet_or_supplement", "comparator": "Placebo", "dose_regimen": null, "duration": "12 weeks (mobility scores at week 6 and week 12)", "population": {"n": null, "n_note": null, "breed": null, "age": "senior dogs", "other": "geriatric and senior dogs with reduced mobility"}, "primary_outcome": "Mobility scores from the Liverpool Osteoarthritis in Dogs (LOAD) questionnaire", "result": "Mild, but statistically significant, improvement of the mobility scores for the treatment group at both week 6 (P = 0.03) and week 12 (P = 0.006) compared to the baseline score. No statistical improvement was noted at any time in the placebo group or between the treatment and placebo group.", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "36185794", "slug": null, "doi": null, "title": "Evaluation of Fortetropin in geriatric and senior dogs with reduced mobility.", "year": 2022, "role": "results", "quotes": ["As pets age, quality of life and mobility can be affected by pain of osteoarthritis and age-related muscle atrophy (sarcopenia).", "The purpose of this randomized, double-blinded, placebo-controlled study was to evaluate the effects of Fortetropin, a nonthermal-pasteurized, freeze-dried, fertilized egg yolk product, on mobility in senior dogs.", "Mobility scores were calculated using a standardized and validated client-based survey: the Liverpool Osteoarthritis in Dogs (LOAD) questionnaire.", "Results showed mild, but statistically significant, improvement of the mobility scores for the treatment group at both week 6", " = 0.03) and week 12 (", " = 0.006) compared to the baseline score. No statistical improvement was noted at any time in the placebo group or between the treatment and placebo group."], "quote_scope": "abstract"}], "summary": "A randomized, double-blinded, placebo-controlled study evaluated Fortetropin, a freeze-dried fertilized egg yolk product, on mobility in senior dogs, motivated by age-related muscle atrophy and osteoarthritis pain. Mobility was scored with the owner-completed LOAD questionnaire. The treatment group showed mild but statistically significant improvement from baseline at weeks 6 and 12, whereas the placebo group did not improve and there was no significant difference between treatment and placebo groups.", "notes": "No full text in the corpus: number of dogs, dose and setting are not stated in the abstract. The client-based LOAD survey implies owner-assessed dogs. P values are quoted around inline italic tags in the abstract.", "parent_id": null, "tags": ["supplement", "mobility", "sarcopenia", "fortetropin", "load"], "extracted_by": "claude-subagent-batch-C"}
+{"id": "ly-d6-2-senolytic-nad-precursor-senior-dogs-rct-2024", "name": "LY-D6/2 senolytic and NAD+ precursor combination in senior companion dogs with mild to moderate cognitive impairment", "acronym": "LY-D6/2", "kind": "randomized_controlled_trial", "status": "completed", "setting": "client_owned", "intervention": "LY-D6/2, a proprietary combination of a senolytic (LY-D6) and an NAD+ precursor (LY-D2), given at low or full dose", "intervention_class": "diet_or_supplement", "comparator": "Placebo", "dose_regimen": "NAD+ precursor (or placebo) capsule(s) once daily and the senolytic (or placebo) capsule(s) on two consecutive days each month; low or full dose (amounts not disclosed)", "duration": "6 months (3-month primary endpoint, 6-month secondary endpoint)", "population": {"n": 70, "n_note": "70 enrolled and allocated to placebo, low or full dose; 59 completed the 3-month primary endpoint and 51 the 6-month secondary endpoint; randomized in blocks of 9 (3 per group)", "breed": null, "age": "10 years or older", "other": "companion dogs with mild to moderate cognitive impairment (CADES), weighing more than 6 kg, able to walk independently; recruited from the local community at NC State"}, "primary_outcome": "Change in owner-reported Canine Cognitive Dysfunction Rating (CCDR) scale score and change in activity measured with collar-mounted physical activity monitors at 3 months", "result": "There was a significant difference in CCDR score across treatment groups from baseline to the primary endpoint (p = 0.02) with the largest decrease in the full dose group. No difference was detected between groups using in house cognitive testing, and no significant differences between groups in changes in measured activity. The proportion of dogs that improved in frailty and owner-reported activity and happiness was higher in the full dose group but not significantly; adverse events occurred equally across groups. The authors conclude that LY-D6/2 improves owner-assessed cognitive function over a 3-month period.", "lead_organization": "North Carolina State University College of Veterinary Medicine", "sponsor_or_funder": "Animal Bioscience, Boston MA", "registration": [], "start_year": 2022, "end_year": null, "sources": [{"type": "pmid", "pmid": "38811634", "slug": null, "doi": "10.1038/s41598-024-63031-w", "title": "A randomized, controlled clinical trial demonstrates improved owner-assessed cognitive function in senior dogs receiving a senolytic and NAD+ precursor combination.", "year": 2024, "role": "results", "quotes": ["Age-related decline in mobility and cognition are associated with cellular senescence and NAD + depletion in dogs and people.", "A combination of a novel NAD + precursor and senolytic, LY-D6/2, was examined in this randomized controlled trial.", "Seventy dogs with mild to moderate cognitive impairment were enrolled and allocated into placebo, low or full dose groups.", "Primary outcomes were change in cognitive impairment measured with the owner-reported Canine Cognitive Dysfunction Rating (CCDR) scale and change in activity measured with physical activity monitors.", "Fifty-nine dogs completed evaluations at the 3-month primary endpoint, and 51 reached the 6-month secondary endpoint.", "There was a significant difference in CCDR score across treatment groups from baseline to the primary endpoint (p = 0.02) with the largest decrease in the full dose group.", "No difference was detected between groups using in house cognitive testing. There were no significant differences between groups in changes in measured activity.", "The proportion of dogs that improved in frailty and owner-reported activity levels and happiness was higher in the full dose group than other groups, however this difference was not significant. Adverse events occurred equally across groups.", "We conclude that LY-D6/2 improves owner-assessed cognitive function over a 3-month period and may have broader, but more subtle effects on frailty, activity and happiness as reported by owners."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "38811634", "slug": null, "doi": "10.1038/s41598-024-63031-w", "title": "A randomized, controlled clinical trial demonstrates improved owner-assessed cognitive function in senior dogs receiving a senolytic and NAD+ precursor combination.", "year": 2024, "role": "design", "quotes": ["Companion dogs aged 10 years or older were randomized to receive either placebo or LY-D6/2 combination at two different doses (low and full) with primary outcomes of change in owner assessed cognition and collar mounted physical activity monitor (PAM) assessed activity levels after 3 months.", "This blinded, randomized, controlled (RCT) clinical trial was conducted and reported according to the CONSORT and ARRIVE Guidelines with the approval of the North Carolina State University Institutional Animal Care and Use Committee under protocol # 21-376-O.", "This 3-arm RCT was designed to evaluate the effect of LY-D6/2 on cognitive function and activity in aged dogs over a 6-month period. The primary endpoint of the study was 3 months and the secondary endpoint was 6 months.", "Dogs were randomized in blocks of 9 (3 per group) by the NC State pharmacy using a random number generator. Investigators and owners were blinded to treatment identity until data analysis was complete.", "In order to participate, dogs had to be greater than or equal to 10 years of age (senior status), weigh more than 6 kg (dictated by available capsule size), and be able to walk independently with sufficient hearing and vision to be able to perform cognitive tests.", "The investigational veterinary product (IVP), LY-D6/2 was a proprietary combination of a senolytic and an NAD+ precursor.", "Owners were instructed to administer the NAD+ precursor (or placebo) capsule(s) once daily and the senolytic (or placebo) capsule(s) on two consecutive days each month.", "Dogs were recruited from the local community through postings on the NC State CVM clinical trials website and social media from January 2022 through June 2023.", "This clinical trial was funded by Animal Bioscience, Boston MA. Animal Bioscience played no role in data acquisition, analysis or presentation."], "quote_scope": "fulltext"}], "summary": "A blinded, three-arm randomized controlled trial at North Carolina State University enrolled 70 companion dogs aged 10 years or older with mild to moderate cognitive impairment and allocated them to placebo, low-dose or full-dose LY-D6/2, a proprietary senolytic plus NAD+ precursor combination given as a daily NAD+ precursor and a monthly two-day senolytic course, for 6 months. Primary outcomes were owner-rated CCDR score and activity-monitor data at 3 months. CCDR change differed significantly across groups (p = 0.02) with the largest improvement on the full dose, while activity, in-house cognitive tests, frailty and owner-reported happiness did not differ significantly; the trial was funded by Animal Bioscience.", "notes": "Dose amounts are proprietary and not disclosed. Recruitment ran January 2022 through June 2023; no trial registration is mentioned in the full text.", "parent_id": null, "tags": ["senolytic", "nad", "supplement", "cognition", "frailty", "activity", "client-owned"], "extracted_by": "claude-subagent-batch-C"}
+{"id": "cow-placenta-extract-cognition-aged-dogs-rct-2026", "name": "Cow placenta extract (CPE) on cognitive function and oxidative stress in aged client-owned dogs", "acronym": null, "kind": "randomized_controlled_trial", "status": "completed", "setting": "client_owned", "intervention": "Cow placenta extract (CPE) oral capsules", "intervention_class": "diet_or_supplement", "comparator": "Placebo capsules identical in appearance, same dosage, method and duration", "dose_regimen": "200 mg CPE orally for dogs weighing 5-15 kg and 400 mg for dogs over 15 kg, twice daily for 6 months", "duration": "6 months (CSLB at months 2, 4 and 6)", "population": {"n": 88, "n_note": "88 dogs completed the trial and are reported (45 CPE, 43 placebo); 94 enrolled, 3 lost to follow-up, 1 died, 2 excluded for noncompliance", "breed": null, "age": "aged dogs >= 7 years per the abstract; over 8 years of age per the full-text inclusion criteria", "other": "client-owned dogs weighing more than 5 kg with a Canine Social and Learning Behavior Survey (CSLB) score >= 30, recruited from 3 animal clinics in the eastern region of China"}, "primary_outcome": "Canine Social and Learning Behavior Survey (CSLB) score; serum oxidative stress markers (MDA, GSH-Px, GSH and others)", "result": "By month 6, mean CSLB was 35.1 +/- 4.9 in the CPE group vs 41.1 +/- 5.3 in the placebo group (P < .05; Cohen's d = -1.17). The successful therapeutic response was 77.8% in the CPE group vs 9.3% in the placebo group (P < .001). Change in CSLB correlated positively with change in MDA (r = 0.77) and negatively with change in GSH-Px and GSH. The authors conclude a six-month CPE administration improved cognitive function and oxidative stress in aged dogs.", "lead_organization": "Jiangsu Agri-animal Husbandry Vocational College, China (ethics committee); 3 animal clinics in the eastern region of China", "sponsor_or_funder": null, "registration": [], "start_year": 2023, "end_year": 2024, "sources": [{"type": "pmid", "pmid": "42492061", "slug": null, "doi": "10.1093/jvimsj/aalag125", "title": "Effects of cow placenta extract on cognitive function in aged dogs: a randomized controlled trial.", "year": 2026, "role": "results", "quotes": ["Cow placenta extract (CPE) has demonstrated beneficial effects in antiaging; however, its effect on age-related cognitive decline remains unclear.", "To evaluate the potential therapeutic benefits of CPE in improving cognitive function in aged dogs.", "The aged dogs (≥7 years) with a Canine Social and Learning Behavior Survey (CSLB) score of ≥ 30 owned by clients.", "A 6-month randomized controlled trial. Eighty-eight dogs received CPE (n = 45) or placebo (n = 43). Canine Social and Learning Behavior Survey questionnaires were administered, and serum oxidative stress markers were assessed.", "By month 6, the mean ± SD of CSLB was 35.1 ± 4.9 in the CPE group vs 41.1 ± 5.3 (P < .05; Cohen's d = -1.17; 95% CI for d: -1.63 to -0.72) in the placebo group.", "The successful therapeutic response was 77.8% (95% CI, 63.2-88.0) in the CPE group vs 9.3% (95% CI, 3.1-22.3; P < .001) in the placebo group.", "The correlation between the change (Δ%) in CSLB and change in malondialdehyde (MDA) was positive (r = 0.77, P < .001), and correlations between the Δ% in CSLB and change in glutathione peroxidase (GSH-Px) and glutathione (GSH) were negative (r = -0.893, P < .001 and r = -0.878, P < .001, respectively).", "A six-month CPE administration improved cognitive function and oxidative stress in aged dogs, suggesting its potential for long-term management of cognitive impairment."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "42492061", "slug": null, "doi": "10.1093/jvimsj/aalag125", "title": "Effects of cow placenta extract on cognitive function in aged dogs: a randomized controlled trial.", "year": 2026, "role": "design", "quotes": ["The experimental plan was submitted to the Ethics Committee of Jiangsu Agri-animal Husbandry Vocational College, China (NSF202108).", "Dogs that were over 8 years of age and weighed more than 5 kg were collected from the databases of 3 different animal clinics in the eastern region of China.", "The period for the baseline CSLB surveys was from December 1, 2023 to January 30, 2024 in this study.", "All participating dogs were randomly assigned to either the CPE group or the placebo group in a 1:1 ratio.", "The investigators and dog owners remained blind to the treatment by ensuring that the appearance of the CPE capsules and the placebo was identical. Dogs weighing between 5 and 15 kg were administered 200 mg of CPE orally, while those weighing over 15 kg received 400 mg of CPE, twice daily for 6 months. The placebo group received a placebo at the same dosage, using the same method and duration.", "At the end of the second (T1), fourth (T2), and sixth (T3) months of administration, the CSLB questionnaire was collected.", "Consequently, 94 dogs were enrolled in the study. Three dogs were lost to follow-up, 1 dog died and 2 dogs were excluded due to noncompliance. Ultimately, 43 dogs of the placebo group and 45 dogs of the CPE group completed the trial (Figure 1)."], "quote_scope": "fulltext"}], "summary": "A 6-month randomized, blinded, placebo-controlled trial in eastern China enrolled client-owned aged dogs (over 7-8 years, more than 5 kg) with a CSLB cognitive score of 30 or more from three animal clinics; 88 dogs completed the trial (45 CPE, 43 placebo). Dogs received cow placenta extract capsules (200 mg for 5-15 kg, 400 mg over 15 kg) or identical placebo twice daily, with CSLB questionnaires and serum oxidative stress markers as outcomes. At month 6 the CPE group had a lower mean CSLB score (35.1 vs 41.1) and a 77.8% response rate versus 9.3% for placebo, and CSLB change correlated with changes in MDA, GSH-Px and GSH.", "notes": "Start year is the baseline survey window (December 2023 to January 2024); end year 2024 follows from the 6-month duration after baseline. The abstract gives the age criterion as >= 7 years while the full text says over 8 years. No funding source is named beyond the project covering veterinary examination costs.", "parent_id": null, "tags": ["supplement", "placenta-extract", "cognition", "oxidative-stress", "cslb", "client-owned"], "extracted_by": "claude-subagent-batch-C"}
+{"id": "dog-aging-project", "name": "Dog Aging Project (DAP) long-term longitudinal study of ageing in companion dogs", "acronym": "DAP", "kind": "longitudinal_cohort", "status": "ongoing", "setting": "client_owned", "intervention": null, "intervention_class": "none", "comparator": null, "dose_regimen": null, "duration": "Long-term; data and biospecimens collected annually, with dogs enrolled for the dog's lifetime", "population": {"n": 30000, "n_note": "Over 30,000 canine participants and their owners at the time of the 2022 design paper, described as tens of thousands of companion dogs; five overlapping cohorts (Pack, Foundation, Precision, TRIAD and a cross-sectional Centenarian sample)", "breed": "All breeds (both purebred and mixed breed)", "age": "All ages", "other": "All sizes and sexes (intact and sterilized); privately owned dogs; participation open to all geographical regions in the USA"}, "primary_outcome": "Identify the genetic, environmental and lifestyle factors associated with healthy lifespan; characterize ageing on multimorbidity, frailty and inflammageing; whole-genome sequencing of at least 10,000 dogs; metabolome, epigenome and microbiome biomarkers of ageing", "result": null, "lead_organization": null, "sponsor_or_funder": "National Institute on Aging (NIA U19 AG057377), as cited in the funding statement of the 2023 Texas A&M rapamycin trial", "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "35110758", "slug": null, "doi": "10.1038/s41586-021-04282-9", "title": "An open science study of ageing in companion dogs.", "year": 2022, "role": "design", "quotes": ["The Dog Aging Project is a long-term longitudinal study of ageing in tens of thousands of companion dogs.", "they offer a unique opportunity to identify the genetic, environmental and lifestyle factors associated with healthy lifespan", "the Dog Aging Project will collect extensive survey data, environmental information, electronic veterinary medical records, genome-wide sequence information, clinicopathology and molecular phenotypes derived from blood cells, plasma and faecal samples"], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "35110758", "slug": null, "doi": "10.1038/s41586-021-04282-9", "title": "An open science study of ageing in companion dogs.", "year": 2022, "role": "design", "quotes": ["along with over 30,000 canine participants and their owners", "The DAP includes observational studies, combining both retrospective cross-sectional and prospective longitudinal data, as well as a randomized, placebo-controlled clinical trial for healthy ageing. Data and biospecimens will be collected annually and made available as a public resource.", "The target study population consists of dogs of all breeds (both purebred and mixed breed), ages, sizes and sexes (males and females, intact and sterilized).", "Structurally, the DAP can be considered as five overlapping cohorts or groups of dogs", "Once enrolled, dogs are members of the Pack for the dog’s lifetime, unless the owner chooses to withdraw.", "The sampled cohorts include Foundation, Precision and TRIAD (Test of Rapamycin In Ageing Dogs), as well as a cross-sectional sample of extremely old ‘Centenarian’ dogs", "Currently, participation in the DAP is open to all geographical regions in the USA", "The DAP has four primary scientific aims. These include (1) characterizing ageing in companion dogs on three separate axes: multimorbidity, frailty and inflammageing; (2) using low-coverage whole-genome sequencing with imputation on at least 10,000 dogs to analyse the genetic architecture of age-related traits in dogs; (3) collecting metabolome, epigenome and microbiome profiles to develop biomarkers of ageing in dogs", "As this is a community science project and all study subjects are privately owned dogs", "Our goal is that the DAP continues indefinitely", "Access to Terra will be provided to users once they sign the DAP data use agreement"], "quote_scope": "fulltext"}, {"type": "pmid", "pmid": "37275618", "slug": null, "doi": "10.3389/fvets.2023.1168711", "title": "A masked, placebo-controlled, randomized clinical trial evaluating safety and the effect on cardiac function of low-dose rapamycin in 17 healthy client-owned dogs.", "year": 2023, "role": "related", "quotes": ["Additional support for some authors was provided by the Dog Aging Project (NIA U19 AG057377"], "quote_scope": "fulltext"}], "summary": "The Dog Aging Project is a long-term, open-data longitudinal study of ageing in tens of thousands of privately owned companion dogs of all breeds, ages, sizes and sexes across the USA, with over 30,000 participants at the time of the 2022 design paper. It collects survey, environmental, veterinary-record, genome-sequence, clinicopathology and molecular data annually for the dog's lifetime, aiming to identify genetic, environmental and lifestyle factors associated with healthy lifespan and to characterize multimorbidity, frailty and inflammageing. The project comprises five overlapping cohorts, including the TRIAD rapamycin trial and the Precision cohort, which are recorded separately; no results are reported in the design paper.", "notes": "Design paper. The TRIAD randomized trial (triad-rapamycin) and the Precision cohort (dog-aging-project-precision-cohort) are recorded separately. The lead institution is not named in the sources (more than 20 academic institutions participate); the NIA grant number is quoted from another paper's funding statement. Data are released on the Terra platform under a data use agreement.", "parent_id": null, "tags": ["cohort", "dog-aging-project", "open-data", "longitudinal", "biomarkers", "genomics"], "extracted_by": "claude-subagent-batch-A"}
+{"id": "old-dog-padua-cohort", "name": "OLD-DOG Project: 30-month prospective biomarkers-of-aging cohort of 209 companion dogs (University of Padua)", "acronym": "OLD-DOG", "kind": "longitudinal_cohort", "status": "ongoing", "setting": "client_owned", "intervention": null, "intervention_class": "none", "comparator": null, "dose_regimen": null, "duration": "30-month prospective study with comprehensive evaluations every six months", "population": {"n": 209, "n_note": "209 privately owned dogs enrolled and assessed at baseline; survival status available for 206 dogs at the fourth time point", "breed": "Multi-breed cohort", "age": "Aged 5 years and over (dogs aged over five years with at least the month of birth known)", "other": "Located in the Veneto region of Italy; absence of acute disease symptoms at the time of each evaluation"}, "primary_outcome": "Identification and validation of biomarkers of aging (physiological, biochemical, hematological and behavioral parameters, microbiota profiles, telomere length, DNA methylation) and their predictive value for healthspan and lifespan", "result": "Preliminary cross-sectional analyses have identified consistent age-related patterns across multiple domains, including hematological and biochemical indices, inflammatory markers, and measures of physical and cognitive performance. The frailty index showed a moderate correlation with chronological age (ρ=0.56, p < .0001); of the 206 dogs for which survival status was available, 29 had died by the fourth time point. Longitudinal analyses are ongoing.", "lead_organization": "University of Padua's Veterinary Teaching Hospital", "sponsor_or_funder": "Italian Ministry of University and Research (MUR), PRIN grant 20228NKPNH", "registration": [], "start_year": 2023, "end_year": null, "sources": [{"type": "pmid", "pmid": "41860870", "slug": null, "doi": "10.1016/j.tjfa.2026.100145", "title": "OLD DOG - Validating the dog as an animal model for human aging studies.", "year": 2026, "role": "design", "quotes": ["The OLD-DOG Project, launched in 2023 at the University of Padua's Veterinary Teaching Hospital, is a 30-month prospective study designed to identify and validate biomarkers of aging in companion dogs and to assess their predictive value for healthspan and lifespan", "A cohort of 209 privately owned dogs aged  ≥ 5 years was enrolled and underwent comprehensive evaluations every six months, including clinical examinations, physical fitness testing, blood and fecal sampling, and owner questionnaires.", "Collected data encompass physiological, biochemical, hematological, and behavioral parameters, as well as microbiota profiles, telomere length, and DNA methylation patterns.", "Preliminary cross-sectional analyses have identified consistent age-related patterns across multiple domains, including hematological and biochemical indices, inflammatory markers, and measures of physical and cognitive performance.", "Ongoing longitudinal analyses aim to determine the predictive value of these candidate biomarkers for morbidity and mortality"], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "41860870", "slug": null, "doi": "10.1016/j.tjfa.2026.100145", "title": "OLD DOG - Validating the dog as an animal model for human aging studies.", "year": 2026, "role": "results", "quotes": ["The OLD-DOG Project is a 30-month prospective observational study designed to identify biomarkers of aging in companion dogs. A total of 209 privately owned dogs were enrolled and assessed at baseline, with follow-up evaluations every six months. All the dogs recruited are located in the Veneto region of Italy.", "Dogs aged over five years, with at least the month of birth known", "Absence of acute disease symptoms at the time of each evaluation", "in a multi-breed canine cohort", "Of the 206 dogs for which survival status was available, 29 had died by the fourth time point.", "The index exhibits a right-skewed distribution and a moderate correlation with chronological age (ρ=0.56, *p* < .0001).", "The study was approved by the ethical committee of the University of Padua. Protocol number: 215906 released on 31/10/2023.", "The following study has been funded by the Italian ministry of university, and research (MUR) with a grant PROGETTO DI RICERCA DI RILEVANTE INTERESSE NAZIONALE (PRIN) 20228NKPNH OLD DOG - Validating the dog as animal model for human ageing studies."], "quote_scope": "fulltext"}], "summary": "The OLD-DOG Project, launched in 2023 at the University of Padua's Veterinary Teaching Hospital, is a 30-month prospective observational study of 209 privately owned, multi-breed dogs aged 5 years and over from the Veneto region of Italy, evaluated every six months with clinical examinations, physical fitness testing, blood and fecal sampling and owner questionnaires. Its purpose is to identify and validate biomarkers of aging and assess their predictive value for healthspan and lifespan. Preliminary cross-sectional analyses show consistent age-related patterns in hematological and biochemical indices, inflammatory markers and physical and cognitive performance, the frailty index correlates moderately with age, and 29 of 206 dogs had died by the fourth time point; longitudinal analyses are ongoing.", "notes": "Observational cohort with no intervention. Ethics approval by the University of Padua ethical committee (protocol number 215906, released 31/10/2023) is not a trial registry entry. End year not stated.", "parent_id": null, "tags": ["cohort", "biomarkers", "frailty", "italy", "longitudinal", "biological-age"], "extracted_by": "claude-subagent-batch-A"}
+{"id": "rapamycin-10-week-rct-2017", "name": "Short-term (10-week) rapamycin randomized controlled trial in 24 middle-aged companion dogs", "acronym": null, "kind": "randomized_controlled_trial", "status": "completed", "setting": "client_owned", "intervention": "Rapamycin at a non-immunosuppressive dose", "intervention_class": "drug", "comparator": "placebo", "dose_regimen": "0.05 mg/kg three times weekly in one rapamycin treatment group and 0.1 mg/kg three times weekly in another rapamycin treatment group (as described in the 2023 Texas A&M follow-up trial); the 2017 abstract states only a non-immunosuppressive dose for 10 weeks", "duration": "10 weeks", "population": {"n": 24, "n_note": "24 middle-aged healthy dogs received either placebo or rapamycin", "breed": null, "age": "Middle-aged; mean age of 9.7 years (as reported in the 2023 follow-up trial)", "other": "Healthy pet dogs"}, "primary_outcome": "Safety of low-dose rapamycin (clinical and hematological exams before, during and after the trial) and echocardiographic measures of heart function before and after the trial", "result": "No clinical side effects in the rapamycin-treated group compared to dogs receiving the placebo. Echocardiography suggested improvement in both diastolic and systolic age-related measures of heart function (E/A ratio, fractional shortening, and ejection fraction) in the rapamycin-treated dogs. Hematological values remained within the normal range for all parameters studied; however, the mean corpuscular volume (MCV) was decreased in rapamycin-treated dogs.", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "28374166", "slug": null, "doi": "10.1007/s11357-017-9972-z", "title": "A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs.", "year": 2017, "role": "results", "quotes": ["In this study, 24 middle-aged healthy dogs received either placebo or a non-immunosuppressive dose of rapamycin for 10 weeks.", "All dogs received clinical and hematological exams before, during, and after the trial and echocardiography before and after the trial.", "Our results showed no clinical side effects in the rapamycin-treated group compared to dogs receiving the placebo.", "Echocardiography suggested improvement in both diastolic and systolic age-related measures of heart function (E/A ratio, fractional shortening, and ejection fraction) in the rapamycin-treated dogs.", "Hematological values remained within the normal range for all parameters studied; however, the mean corpuscular volume (MCV) was decreased in rapamycin-treated dogs.", "Based on these results, we will test rapamycin on a larger dog cohort for a longer period of time in order to validate its effects on cardiac function and to determine whether it can significantly improve healthspan and reduce mortality in companion dogs."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "37275618", "slug": null, "doi": "10.3389/fvets.2023.1168711", "title": "A masked, placebo-controlled, randomized clinical trial evaluating safety and the effect on cardiac function of low-dose rapamycin in 17 healthy client-owned dogs.", "year": 2023, "role": "follow-up", "quotes": ["Previously, our group investigated low-dose rapamycin and placebo treatments in healthy, middle-aged dogs over a 10-week period, with the primary goal of establishing the safety of low-dose rapamycin in healthy pet dogs.", "Interestingly, this trial found that FS improved in treated dogs, although a statistically significant change in EF was not detected, over the 10-week study period.", "which showed significantly higher FS and E/A ratio in dogs treated with a shorter duration but higher dose of rapamycin compared to a placebo group in a randomized controlled trial", "Dogs in the previous trial received 0.05 mg/kg three times weekly in one rapamycin treatment group and 0.1 mg/kg three times weekly in another rapamycin treatment group (both compared to a placebo group in that trial)", "Additionally, dogs in the previous trial had a mean age of 9.7 years"], "quote_scope": "fulltext"}], "summary": "Twenty-four middle-aged healthy pet dogs received placebo or a non-immunosuppressive dose of rapamycin for 10 weeks in a randomized controlled trial whose primary goal was establishing safety, with echocardiography before and after treatment. No clinical side effects were seen in the rapamycin group, and echocardiography suggested improvement in diastolic and systolic age-related measures of heart function (E/A ratio, fractional shortening, ejection fraction). Hematology stayed within normal ranges apart from a decreased mean corpuscular volume in treated dogs. A companion pharmacokinetic study in 5 healthy purpose-bred hounds showed that oral low-dose (0.1 mg/kg) rapamycin achieved blood concentrations measurable in nanograms per milliliter.", "notes": "The 2016 pharmacokinetic paper (5 purpose-bred hounds, 0.1 mg/kg orally, University of Tennessee IACUC) is grouped here as the pharmacokinetic companion per the registry's grouping decision; its abstract frames its purpose around tumor-bearing dogs and does not itself reference the 10-week trial. Dose groups, randomization wording and mean age of the 10-week trial are taken from the 2023 Texas A&M follow-up trial's description of the prior trial; the 2017 abstract itself does not name the dose, the lead institution or the funder. The low-dose rapamycin pharmacokinetic study (PMID 26709938; University of Tennessee, 5 purpose-bred hounds) is a separate study and is not a source of this record.", "parent_id": null, "tags": ["rapamycin", "cardiac-function", "safety", "companion-dogs", "short-term", "pharmacokinetics"], "extracted_by": "claude-subagent-batch-A"}
+{"id": "rapamycin-6-month-rct-tamu-2023", "name": "Six-month low-dose rapamycin masked placebo-controlled randomized trial in 17 healthy client-owned dogs (Texas A&M)", "acronym": null, "kind": "randomized_controlled_trial", "status": "completed", "setting": "client_owned", "intervention": "Low-dose rapamycin", "intervention_class": "drug", "comparator": "Placebo (lactose capsules identical in appearance)", "dose_regimen": "0.025 mg/kg rapamycin per dose, orally in capsules, three times per week (Monday, Wednesday and Friday mornings), rounded to the nearest 0.25 mg capsule", "duration": "6 months of treatment; evaluations at baseline, 3, 6 and 12 months (final examination 6 months after discontinuation)", "population": {"n": 17, "n_note": "17 dogs enrolled and randomized: 9 rapamycin, 8 placebo; the initial design sought 50 dogs but enrollment ceased early", "breed": null, "age": "6-10 years (mean 7.8 years in the rapamycin group and 8.5 years in the placebo group)", "other": "Weighing 18-36 kg, without significant systemic disease; all enrolled dogs resided in Texas; diverse breeds"}, "primary_outcome": "Echocardiographic indices of diastolic and systolic cardiac function at 6 and 12 months, and occurrence of adverse events; impact on routine clinical pathology was a secondary objective", "result": "There were no statistically significant differences in echocardiographic parameters between rapamycin and placebo groups at 6 or 12 months. No clinically significant adverse events occurred. In 26.8% of the bi-weekly surveys owners whose dogs received rapamycin reported perceived positive changes in behavior or health, compared to 8.1% in the placebo group (p = 0.04). The drug was well-tolerated with no significant adverse events.", "lead_organization": "Texas A&M University (TAMU) Veterinary Medical Teaching Hospital (VMTH)", "sponsor_or_funder": "William H. Donner Foundation; additional support for some authors from the Dog Aging Project (NIA U19 AG057377)", "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "37275618", "slug": null, "doi": "10.3389/fvets.2023.1168711", "title": "A masked, placebo-controlled, randomized clinical trial evaluating safety and the effect on cardiac function of low-dose rapamycin in 17 healthy client-owned dogs.", "year": 2023, "role": "results", "quotes": ["The objectives of this study were to assess the impact of 6 months of low-dose rapamycin on echocardiographic indices of cardiac function in healthy dogs and to document the occurrence of adverse events.", "Seventeen client-owned dogs aged 6-10 years, weighing 18-36 kg, and without significant systemic disease were included in a prospective, randomized, placebo-controlled, masked clinical trial.", "Low-dose rapamycin (0.025 mg/kg) or placebo was administered three times per week for 6 months.", "Baseline, 6-month, and 12-month evaluation included physical examination, cardiology examination, and clinicopathology.", "There were no statistically significant differences in echocardiographic parameters between rapamycin and placebo groups at 6 or 12 months. No clinically significant adverse events occurred.", "In 26.8% of the bi-weekly surveys owners whose dogs received rapamycin reported perceived positive changes in behavior or health, compared to 8.1% in the placebo group", "While no clinically significant change in cardiac function was observed in dogs treated with low-dose rapamycin, the drug was well-tolerated with no significant adverse events."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "37275618", "slug": null, "doi": "10.3389/fvets.2023.1168711", "title": "A masked, placebo-controlled, randomized clinical trial evaluating safety and the effect on cardiac function of low-dose rapamycin in 17 healthy client-owned dogs.", "year": 2023, "role": "design", "quotes": ["This study was a prospective, randomized, placebo-controlled double-masked trial conducted at the Texas A&M University (TAMU) Veterinary Medical Teaching Hospital (VMTH).", "Placebo (lactose; PCCA, Houston, TX) capsules were created to be identical in appearance. Dogs in the treatment group were given 0.025 mg/kg rapamycin per dose, rounded to the nearest 0.25 mg capsule. Owners were instructed to give the study medication on Monday, Wednesday, and Friday mornings.", "Administration of rapamycin and placebo was continued for a period of 6 months.", "A final examination was performed at 12 months (6 months after discontinuation of study medication) to determine whether any changes induced by rapamycin therapy persisted beyond the treatment period.", "17 dogs were enrolled and randomly assigned to rapamycin or placebo groups.", "six out of nine rapamycin-treated dogs, and five out of eight placebo-treated dogs", "the mean age in the present trial was 7.8 years for the treatment group and 8.5 years for the placebo group", "Because all enrolled dogs resided in Texas", "The diversity of the breeds enrolled may have been a contributing factor as well.", "Assessment of the impact of low-dose rapamycin on routine clinical pathology was a secondary objective.", "This frequency of positive owner-reported outcomes in the rapamycin treatment group was significantly greater than in the placebo group (*p* = 0.04).", "The initial study design sought to enroll 50 dogs (25 placebo, 25 rapamycin) based on power calculations. Several factors caused us to cease enrollment early, limiting the power to detect significant changes in the primary endpoint. These factors included difficulty identifying eligible dogs near the clinical site and the launch of the larger, multi-center clinical trial described below.", "This study was funded by the William H. Donner Foundation. Additional support for some authors was provided by the Dog Aging Project (NIA U19 AG057377; BB, DP, MK, JE, LC, and KC).", "Institutional Animal Care and Use Committee (IACUC) and Clinical Research Review Committee protocol number 2017–0125."], "quote_scope": "fulltext"}], "summary": "Seventeen healthy client-owned dogs aged 6-10 years and weighing 18-36 kg were randomized at the Texas A&M veterinary teaching hospital to low-dose rapamycin (0.025 mg/kg three times per week) or identical placebo capsules for 6 months, with echocardiography and clinical pathology at baseline, 6 and 12 months. There were no statistically significant differences in echocardiographic parameters between groups at 6 or 12 months and no clinically significant adverse events. Owners of rapamycin-treated dogs reported perceived positive changes in behavior or health in 26.8% of bi-weekly surveys versus 8.1% for placebo (p = 0.04). Enrollment stopped early at 17 of a planned 50 dogs.", "notes": "The IACUC and Clinical Research Review Committee protocol number 2017–0125 is an ethics approval, not a trial registry entry. Enrollment ceased early (17 of a planned 50 dogs) because of recruitment difficulty and the launch of the multi-center TRIAD trial. This paper is also cited as a follow-up source in rapamycin-10-week-rct-2017 and as a design source in triad-rapamycin.", "parent_id": null, "tags": ["rapamycin", "cardiac-function", "safety", "client-owned", "placebo-controlled", "texas-a-m"], "extracted_by": "claude-subagent-batch-A"}
+{"id": "ashwagandha-gut-parameters-geriatric-beagles-rct-2024", "name": "Ashwagandha root extract on gut parameters in healthy geriatric research Beagles", "acronym": null, "kind": "randomized_controlled_trial", "status": "completed", "setting": "laboratory_colony", "intervention": "Withania somnifera/Ashwagandha root extract (ARE; KSM-66) capsules", "intervention_class": "diet_or_supplement", "comparator": "Placebo (starch-filled capsules identical in appearance)", "dose_regimen": "15 mg/kg body weight, once daily, orally, for 2 months", "duration": "2 months (assessed on day 0, day 30 and day 60)", "population": {"n": 12, "n_note": "6 placebo and 6 ARE", "breed": "Beagle", "age": "12-15 years", "other": "healthy geriatric dogs bred for research purposes, approximately 11 kg, housed at a certified kennel in Hyderabad, Telangana, India"}, "primary_outcome": "Serum haematology, biochemical markers, stool parameters (faecal score and pH) and gut-microbiome parameters (faecal short chain fatty acids, L-citrulline, intestinal-type alkaline phosphatase, lactate, carbamoyl-phosphate synthase)", "result": "Erythrocyte counts and haemoglobin were significantly increased with ARE; serum ALT and AST significantly decreased at day 60 compared with placebo; L-citrulline was significantly modulated while I-ALP, lactate and CPS were unaffected; faecal score reduced significantly (p < 0.001) while faecal pH was unaltered; propionic acid and total SCFAs decreased from baseline after 60 days while butyrate and acetic acid were unchanged. The authors suggest ARE has gut health promoting benefits in healthy geriatric dogs, reducing age-related changes by modulating the microbiome and its metabolites.", "lead_organization": null, "sponsor_or_funder": "KSM-66 ashwagandha root extract and corn starch placebo provided as gift samples by Ixoreal BioMed, Inc., Los Angeles, CA (no other funding stated)", "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "39911483", "slug": null, "doi": "10.3389/fvets.2024.1491989", "title": "The role of Ashwagandha in modulating gut parameters in dogs-a randomized double-blind placebo-controlled trial.", "year": 2024, "role": "results", "quotes": ["/Ashwagandha root extract (ARE) on important gut-microbiome parameters in healthy geriatric dogs.", "We hypothesized that ARE might promote a healthy gut by its adaptogenic and anti-inflammatory effects and improve vital parameters for healthy ageing.", "A randomized, double-blind, placebo-controlled trial was conducted in Telangana, India. Twelve healthy geriatric Beagle dogs aged 12-15 years were enrolled.", "The dogs were divided into two groups to receive ARE (15 mg/kg, once daily, orally, for 2 months) or a placebo control.", "Various parameters were assessed, including serum haematology, biochemical markers, stool parameters, and gut-microbiome parameters.", "The erythrocyte counts and haemoglobin levels were significantly increased with ARE (", "In addition, the levels of L-citrulline were significantly modulated by ARE intervention, whereas the intervention did not affect intestinal-type alkaline phosphatase (I-ALP), lactate, and carbamoyl-phosphate synthase (CPS).", "Interestingly, the faecal score reduced significantly with ARE (", "), while the faecal pH remained unaltered.", "Compared to the baseline, ARE significantly decreased two microbial metabolites, propionic acid, and total short chain fatty acids (SCFAs) levels after 60 days of intervention, whereas butyrate and acetic acid levels remained unchanged in the faecal samples.", "In summary, these findings suggest that ARE has gut health promoting benefits in healthy geriatric dogs by improving haematological and biochemical profiles; the levels of L-citrulline; propionic acid; and SCFA; thus, reducing age-related changes by modulating the microbiome and the associated metabolites."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "39911483", "slug": null, "doi": "10.3389/fvets.2024.1491989", "title": "The role of Ashwagandha in modulating gut parameters in dogs-a randomized double-blind placebo-controlled trial.", "year": 2024, "role": "design", "quotes": ["The study was conducted on 12–15-year-old beagle dogs bred for research purposes (*n* = 12) weighing approximately 11 kg at study initiation which were randomly divided into placebo (*n* = 6) and ARE (*n* = 6) groups.", "The study was conducted at a certified kennel in Hyderabad, Telangana, India.", "The placebo group received starch-filled capsules identical to ARE’s appearance, color, odor and taste (KSM-66).", "The study dogs received either ARE or placebo in the form of capsules daily once, orally at a dose of 15 mg/kg body weight.", "The study was approved by the local Institutional Animal Ethics Committee (IAEC) and the central government’s Committee for Control and Supervision of Experiments on Animals (CCSEA), New Delhi, India, vide approval number: 03/LA/CVSC-WGL/2023.", "The study was conducted using high withanolides concentration (>5%) enriched KSM-66 Ashwagandha root extract (ARE) and corn starch (placebo) which were provided as gift samples by Ixoreal BioMed, Inc., Los Angeles, CA, United States.", "a significant decrease in important serum liver biomarkers (alanine transaminase [ALT], aspartate transaminase [AST];"], "quote_scope": "fulltext"}], "summary": "A randomized, double-blind, placebo-controlled trial in Telangana, India randomly divided 12 healthy geriatric research Beagles aged 12-15 years, housed at a certified kennel, into ARE (KSM-66 ashwagandha root extract, 15 mg/kg orally once daily for 2 months; n = 6) and starch placebo (n = 6) groups, hypothesising that ARE would improve vital parameters for healthy ageing through the gut. Haematology, biochemistry, stool parameters and faecal metabolites were assessed on days 0, 30 and 60. ARE increased erythrocytes and haemoglobin, lowered ALT and AST at day 60 versus placebo, reduced faecal score, modulated L-citrulline and lowered propionic acid and total SCFAs from baseline.", "notes": "Separate from the client-owned Labrador ashwagandha trial (PMID 39078383); different animals, kennel setting and a 2023 ethics approval. Lead organization not stated explicitly in the extracted text (ethics approval number references CVSC-WGL).", "parent_id": null, "tags": ["supplement", "ashwagandha", "gut", "microbiome", "scfa", "beagle", "colony"], "extracted_by": "claude-subagent-batch-C"}
+{"id": "beagle-middle-aged-enrichment-tacrolimus-q134r-brain-atrophy", "name": "Behavioral enrichment with tacrolimus or Q134R in middle-aged beagles: longitudinal MRI brain atrophy study", "acronym": null, "kind": "longitudinal_cohort", "status": "completed", "setting": null, "intervention": "Chronic treatment with the calcineurin inhibitor tacrolimus or the NFAT-inhibiting compound Q134R, in dogs undergoing behavioral enrichment", "intervention_class": "combination", "comparator": null, "dose_regimen": null, "duration": null, "population": {"n": 43, "n_note": "36 females, 7 males", "breed": "Beagle", "age": "middle-aged", "other": null}, "primary_outcome": "Age-related brain atrophy on annual MRI (region-of-interest-based and voxel-based volumetrics of frontal lobe, caudate nucleus and hippocampus)", "result": "We found that the frontal lobe showed accelerated atrophy with age, while the caudate nucleus remained relatively stable. Remarkably, the hippocampus increased in volume in all dogs. None of these changes were influenced by tacrolimus or Q134R treatment. Our results suggest that behavioral enrichment can prevent atrophy and increase the volume of the hippocampus but does not prevent aging-associated prefrontal cortex atrophy.", "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "38561226", "slug": null, "doi": "10.1523/jneurosci.2366-23.2024", "title": "Age-Related Brain Atrophy and the Positive Effects of Behavioral Enrichment in Middle-Aged Beagles.", "year": 2024, "role": "results", "quotes": ["Here we examined the effects of chronic treatment with the calcineurin inhibitor (CNI) tacrolimus or the nuclear factor of activated T cells (NFAT)-inhibiting compound Q134R on age-related canine brain atrophy from a longitudinal study in middle-aged beagles (36 females, 7 males) undergoing behavioral enrichment.", "Annual MRI was analyzed using modern, automated techniques for region-of-interest-based and voxel-based volumetric assessments.", "We found that the frontal lobe showed accelerated atrophy with age, while the caudate nucleus remained relatively stable. Remarkably, the hippocampus increased in volume in all dogs. None of these changes were influenced by tacrolimus or Q134R treatment.", "Our results suggest that behavioral enrichment can prevent atrophy and increase the volume of the hippocampus but does not prevent aging-associated prefrontal cortex atrophy."], "quote_scope": "abstract"}], "summary": "A longitudinal study followed 43 middle-aged beagles (36 females, 7 males) undergoing behavioral enrichment and chronically treated with tacrolimus or Q134R, with annual MRI analysed by automated regional and voxel-based volumetrics. The frontal lobe atrophied at an accelerating rate with age, the caudate nucleus stayed relatively stable, and the hippocampus increased in volume in all dogs. Neither drug influenced these changes, which the authors attribute to behavioral enrichment preventing hippocampal atrophy without preventing prefrontal atrophy.", "notes": "Kind follows the abstract's wording (a longitudinal study in middle-aged beagles undergoing behavioral enrichment); the study also chronically treats dogs with tacrolimus or Q134R, but the abstract does not describe the treatment arms, comparator, dosing or study length, so those fields are null. Separate from the earlier aged-beagle antioxidant/enrichment study.", "parent_id": null, "tags": ["brain-aging", "enrichment", "mri", "beagle", "tacrolimus", "q134r", "longitudinal"], "extracted_by": "claude-subagent-batch-B"}
+{"id": "loyal-stay-loy-002", "name": "STAY study: LOY-002 for healthy lifespan extension in senior dogs (Loyal)", "acronym": "STAY", "kind": "regulatory_program", "status": "ongoing", "setting": "client_owned", "intervention": "LOY-002, a prescription daily pill targeting age-related metabolic dysfunction", "intervention_class": "drug", "comparator": "placebo", "dose_regimen": "daily oral tablet (dose not disclosed)", "duration": "four-year study", "population": {"n": 1300, "n_note": "enrolment completed July 2025 at 70 veterinary clinics in the US (initial goal 1,000 dogs, expanded by 300)", "breed": "any; dogs of nearly every size", "age": "10 years or older, weighing at least 14 lb", "other": null}, "primary_outcome": "lifespan and quality of life compared with placebo; adverse effects", "result": null, "lead_organization": "Loyal (San Francisco)", "sponsor_or_funder": "Loyal", "registration": [], "start_year": 2024, "end_year": null, "sources": [{"type": "web", "pmid": null, "slug": "dvm360-stay-enrollment", "doi": null, "title": "Clinical trial for Longevity drug meets goal of enrolling 1000 dogs (dvm360)", "year": 2025, "role": "press", "quotes": ["The STAY study, a clinical trial investigating the developmental longevity drug LOY-002, has reached its goal of enrolling 1000 canine patients at 70 veterinary clinics across the US.", "this 4-year study may be the world’s largest veterinary clinical trial, and a new goal has been set for expanding the trial to include an additional 300 patients.", "Dogs age 10 years or older and weighing at least 14 pounds are eligible.", "Loyal is collecting data on the drug’s potential impact on the lifespan and quality of life for dogs receiving LOY-002, compared to those receiving a placebo, as well as any adverse effects reported in the study population."], "quote_scope": "web"}, {"type": "web", "pmid": null, "slug": "dvm360-stay-milestone", "doi": null, "title": "Lifespan extension drug in development for senior dogs reaches a new milestone (dvm360)", "year": 2026, "role": "press", "quotes": ["Scientific evidence also included the ongoing STAY study, which completed patient enrollment with 1300 dogs at 70 veterinary clinics across the US in July 2025.", "LOY-002 is a prescription daily pill that targets age-related metabolic dysfunction and is designed to improve quality of life in canines 10 years and older, weighing at least 14 lb."], "quote_scope": "web"}, {"type": "web", "pmid": null, "slug": "yahoo-loyal-safety-acceptance", "doi": null, "title": "Loyal Receives FDA Acceptance of Safety Package for Senior Dog Lifespan Extension Drug (company release, 2026-01-13)", "year": 2026, "role": "company", "quotes": ["announced today that the FDA's Center for Veterinary Medicine (CVM) has accepted the Target Animal Safety (TAS) technical section of its conditional approval application for LOY-002", "TAS completion follows on several milestones for LOY-002 in the past year, including the FDA's acceptance of RXE in February 2025.", "LOY-002, a prescription daily pill, aims to extend the healthy lifespan of senior dogs and maintain their quality of life as they age by proactively targeting the underlying metabolic drivers of aging and delaying the onset of disease.", "At 1,300 dogs across 70 veterinary clinics, it's the largest clinical trial in the history of veterinary medicine."], "quote_scope": "web"}, {"type": "web", "pmid": null, "slug": "loyal-for-dog-owners", "doi": null, "title": "Loyal: for dog owners (company page)", "year": 2026, "role": "company", "quotes": ["LOY-002 is our drug for senior dogs , a daily pill intended to help dogs of nearly every size live a longer, healthier life.", "Our dog longevity drugs are all being developed under the FDA Center for Veterinary Medicine’s expanded conditional approval (XCA) pathway."], "quote_scope": "web"}], "summary": "The STAY study is Loyal's pivotal, placebo-controlled, four-year field trial of LOY-002, a daily pill intended to extend healthy lifespan in dogs aged 10 years or older weighing at least 14 lb. Enrolment reached 1,000 dogs at 70 US veterinary clinics and was expanded to 1,300, completing in July 2025. The FDA Center for Veterinary Medicine accepted the reasonable-expectation-of-effectiveness section in February 2025 and the target-animal-safety section in January 2026 under the expanded conditional approval pathway; no efficacy results have been published.", "notes": "Company- and trade-press-sourced; no peer-reviewed publication of design or results as of 2026-10-01. The drug's mechanism and dose are not disclosed beyond 'targets age-related metabolic dysfunction'.", "parent_id": null, "tags": ["lifespan", "drug", "senior-dogs", "pivotal-trial", "fda-conditional-approval", "loyal"], "extracted_by": "claude-hand-curated"}
+{"id": "vaccs-cancer-preventative-vaccine", "name": "Vaccination Against Canine Cancer Study (VACCS)", "acronym": "VACCS", "kind": "randomized_controlled_trial", "status": "ongoing", "setting": "client_owned", "intervention": "Cancer preventative vaccine targeting frameshift neoantigens conserved across multiple species and tumor histologies", "intervention_class": "vaccine", "comparator": "placebo", "dose_regimen": null, "duration": null, "population": {"n": null, "n_note": "Described as the largest interventional cancer clinical trial conducted in companion dogs to date; enrollment number not stated in the abstract", "breed": null, "age": null, "other": "Companion dogs"}, "primary_outcome": "Cumulative incidence (CI) of dogs developing malignant neoplasia of any type at the end of the study period, in addition to safety and immunogenicity; secondary endpoints are changes in incidence of specific tumor types, survival times following neoplasia diagnosis, and all-cause mortality", "result": null, "lead_organization": null, "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "38056066", "slug": null, "doi": "10.1016/j.vetimm.2023.110691", "title": "Design of a randomized, placebo-controlled study evaluating efficacy and safety of a cancer preventative vaccine in dogs.", "year": 2024, "role": "design", "quotes": ["Identification and vaccination against frameshift neoantigens conserved across multiple species and tumor histologies is a potential cancer preventative strategy currently being investigated.", "Companion dogs spontaneously develop cancers at a similar incidence to those in people and are a complementary comparative patient population for the development of novel anti-cancer therapeutics.", "Here we describe the study protocol for the Vaccination Against Canine Cancer Study (VACCS), the largest interventional cancer clinical trial conducted in companion dogs to date.", "In addition to safety and immunogenicity, the primary endpoint of VACCS is the cumulative incidence (CI) of dogs developing malignant neoplasia of any type at the end of the study period.", "Secondary endpoints include changes in incidence of specific tumor types, survival times following neoplasia diagnosis, and all-cause mortality."], "quote_scope": "abstract"}], "summary": "VACCS is a randomized, placebo-controlled study protocol testing a cancer preventative vaccine against frameshift neoantigens in companion dogs, described as the largest interventional cancer clinical trial conducted in companion dogs to date. Its primary endpoint is the cumulative incidence of malignant neoplasia of any type at the end of the study period, alongside safety and immunogenicity, with secondary endpoints of specific tumor incidence, survival after neoplasia diagnosis and all-cause mortality. No results are reported in the protocol paper.", "notes": "Protocol paper. The design wording 'randomized, placebo-controlled' comes from the paper title (Design of a randomized, placebo-controlled study evaluating efficacy and safety of a cancer preventative vaccine in dogs), which the abstract body does not restate; the abstract gives no age range, enrollment number, dose schedule, lead institution, sponsor or registration id. Included under the registry's cancer-prevention criterion.", "parent_id": null, "tags": ["vaccine", "cancer-prevention", "companion-dogs", "ongoing", "neoantigen"], "extracted_by": "claude-subagent-batch-A"}
+{"id": "dog-aging-project-precision-cohort", "name": "Dog Aging Project Precision cohort (multi-omic longitudinal sub-cohort of 1,000 dogs)", "acronym": null, "kind": "longitudinal_cohort", "status": "ongoing", "setting": "client_owned", "intervention": null, "intervention_class": "none", "comparator": null, "dose_regimen": null, "duration": "Annual biospecimen collection; second- and third-year samples already being collected", "population": {"n": 1000, "n_note": "One thousand dog-owner pairs recruited; blood, urine, fecal and hair samples collected and processed from 976 dogs", "breed": null, "age": null, "other": "Recruited into cohort strata based on life stage, sex, size and geography; samples collected by primary care veterinarians"}, "primary_outcome": "Mechanisms underlying age-related change in the metabolome, microbiome and epigenome; data include complete blood count, chemistry profile, immunophenotyping by flow cytometry, metabolite quantification, fecal microbiome characterization, epigenomic profile and urinalysis", "result": "The project demonstrates that scientifically useful biospecimens can be collected from a geographically dispersed population through collaboration with private veterinary clinics and downstream labs; no age-related findings are reported in the design paper.", "lead_organization": "Dog Aging Project", "sponsor_or_funder": null, "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "40038157", "slug": null, "doi": "10.1007/s11357-025-01571-3", "title": "Rationale and design of the Dog Aging Project precision cohort: a multi-omic resource for longitudinal research in geroscience.", "year": 2025, "role": "design", "quotes": ["The Dog Aging Project designed the precision cohort to study the mechanisms underlying age-related change in the metabolome, microbiome, and epigenome in companion dogs", "One thousand dog-owner pairs were recruited into cohort strata based on life stage, sex, size, and geography.", "In collaboration with primary care veterinarians, we collected and processed blood, urine, fecal, and hair samples from 976 dogs.", "The resulting data include complete blood count, chemistry profile, immunophenotyping by flow cytometry, metabolite quantification, fecal microbiome characterization, epigenomic profile, urinalysis, and associated metadata", "The project, which has already begun collecting second- and third-year samples from precision cohort dogs, demonstrates that scientifically useful biospecimens can be collected from a geographically dispersed population through collaboration with private veterinary clinics and downstream labs.", "Most important, the Dog Aging Project is an open data project. We encourage researchers around the world to apply for data access"], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "35110758", "slug": null, "doi": "10.1038/s41586-021-04282-9", "title": "An open science study of ageing in companion dogs.", "year": 2022, "role": "design", "quotes": ["Owners of dogs enrolled in the Precision cohort receive biospecimen kits annually. The biospecimens are collected by each dog’s primary care veterinarian."], "quote_scope": "fulltext"}], "summary": "The Precision cohort is a Dog Aging Project sub-cohort of one thousand dog-owner pairs recruited into strata by life stage, sex, size and geography to study age-related change in the metabolome, microbiome and epigenome of companion dogs. Blood, urine, fecal and hair samples were collected from 976 dogs by primary care veterinarians, yielding blood counts, chemistry, immunophenotyping, metabolite, microbiome, epigenomic and urinalysis data, with kits sent annually and second- and third-year samples already being collected. The design paper reports the feasibility of this collection model rather than age-related results, and the data are open to researchers on application.", "notes": "Sub-study of the Dog Aging Project (parent record dog-aging-project). Funder not stated in the abstract.", "parent_id": "dog-aging-project", "tags": ["cohort", "dog-aging-project", "multi-omic", "biomarkers", "precision-cohort"], "extracted_by": "claude-subagent-batch-A"}
+{"id": "ef-m2-immutalon-geri-vital-dog-rct-2025", "name": "EF-M2 (Immutalon) macrophage glyco-modulation for activity and vitality in aging companion dogs (GERI-VITAL-DOG)", "acronym": "GERI-VITAL-DOG", "kind": "randomized_controlled_trial", "status": "completed", "setting": "client_owned", "intervention": "Subcutaneous EF-M2 (Immutalon), a GcMAF-derived protein for macrophage-targeted glyco-modulation", "intervention_class": "drug", "comparator": "Matched placebo (identical 0.9% sodium chloride vehicle, mirror injections and mirror step-up)", "dose_regimen": "0.1 ug/kg (0.1 mL/kg) subcutaneously every 72 h for 4 weeks, with protocolized blinded step-up to every 48 h at day 14 for partial responders; followed by 4 weeks off-treatment", "duration": "4 weeks of treatment plus 4 weeks off-treatment (assessments to day 56)", "population": {"n": 60, "n_note": "60 randomized (30 EF-M2; 30 placebo), intention-to-treat population", "breed": null, "age": ">= 10 years; mean age 12.4 +/- 1.8 y", "other": "client-owned geriatric dogs, clinically stable, at two referral veterinary clinics in Novosibirsk, Russia"}, "primary_outcome": "Co-primary endpoints tested hierarchically: change in accelerometer-measured active minutes/day at week 1 and change in a day-28 vitality composite (z-score of inverted CBPI-PSS, HRQL-vitality and appetite VAS)", "result": "EF-M2 was superior to placebo on both co-primary endpoints: +23.05 min/day at week 1 (95% CI, 18.16-27.94; p < 0.001) and +2.01 z-units at day 28 (95% CI, 1.52-2.50; p < 0.001). Key secondaries favored EF-M2, including greater week-4 activity (+33.00 min/day), lower BAER auditory threshold (-5.28 dB) and reduced transepidermal water loss. Owner-reported global improvement was 93.3% vs 10.0% at day 28 and 50.0% vs 16.7% at day 56 off-treatment. Adverse events were infrequent, mild and similar to placebo.", "lead_organization": "Center for New Medical Technologies (Novosibirsk, Russia) and Triangel Scientific Research Laboratory (San Francisco, CA, USA); conducted at VEGA Veterinary Clinic and BALTO Veterinary Clinic, Novosibirsk", "sponsor_or_funder": "Activator MAF, LLC (Novosibirsk, Russia): supplied Immutalon and provided unrestricted financial support", "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "41472148", "slug": null, "doi": "10.3390/vetsci12121168", "title": "Precision Glyco-Modulation of Macrophages with EF-M2 (Immutalon&lt;sup&gt;TM&lt;/sup&gt;) Improves Function and Lowers Inflammatory Biomarkers in Aging Dogs: A Double-Blind, Placebo-Controlled Trial.", "year": 2025, "role": "results", "quotes": ["We evaluated whether macrophage-targeted glyco-modulation can improve day-to-day function in aging companion animals.", "In a multicenter, randomized, double-blind, placebo-controlled trial, 60 client-owned geriatric dogs (≥10 years) received subcutaneous EF-M2 (0.1 μg/kg, every 72 h for 4 weeks; protocolized, blinded step-up to every 48 h at day 14 for partial responders) or matched placebo, followed by 4 weeks off-treatment.", "Two prespecified co-primary endpoints were tested hierarchically: change in accelerometer-measured active minutes/day at week 1 and change in a day-28 vitality composite (z-score of inverted CBPI-PSS, HRQL-vitality, and appetite VAS).", "EF-M2 was superior to placebo on both: +23.05 min/day at week 1 (95% CI, 18.16-27.94;", ") and +2.01 z-units at day 28 (95% CI, 1.52-2.50;", "Key secondaries favored EF-M2, including greater week-4 activity (+33.00 min/day, 26.83-39.18;", "lower BAER auditory threshold (-5.28 dB, -7.53 to -3.04;", "Owner-reported global improvement was more frequent with EF-M2 at day 28 (93.3% vs. 10.0%) and remained higher at day 56 off-treatment (50.0% vs. 16.7%).", "Adverse events were infrequent, mild, and similar to placebo; no treatment-related withdrawals or serious events occurred.", "These findings support macrophage-targeted glyco-modulation as a promising approach to rapidly improve real-world activity and multidomain vitality in older dogs, with short-term signals persisting off-treatment; longer, adequately powered trials are warranted to define durability, structural outcomes, and phenotype-specific benefits."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "41472148", "slug": null, "doi": "10.3390/vetsci12121168", "title": "Precision Glyco-Modulation of Macrophages with EF-M2 (Immutalon&lt;sup&gt;TM&lt;/sup&gt;) Improves Function and Lowers Inflammatory Biomarkers in Aging Dogs: A Double-Blind, Placebo-Controlled Trial.", "year": 2025, "role": "design", "quotes": ["GERI-VITAL-DOG was a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial in geriatric dogs (1:1 allocation).", "The trial was conducted at two referral veterinary clinics for companion animals. All study operations (design finalization, conduct, monitoring, data management, and statistical analysis) were performed independently by investigators from the Center for New Medical Technologies (Novosibirsk, Russia) and the Triangel Scientific Research Laboratory (San Francisco, CA, USA).", "Client-owned dogs aged ≥10 years were eligible if clinically stable and if owners consented to have the dog wear an accelerometer for ≥20 h/day.", "was supplied as a sterile, preservative-free aqueous solution of GcMAF-derived EF-M2 protein (1 µg/mL) in 0.9% sodium chloride (normal saline) in 1 mL Type I glass vials.", "The placebo consisted of the identical vehicle (0.9% sodium chloride) without EF-M2, filled into visually indistinguishable vials and administered at the same volume per kilogram and on a schedule mirrored to that of the active regimen, including the protocolized step-up.", "was reviewed and approved by the Institutional Animal Care and Use Committees of both participating veterinary clinics: VEGA Veterinary Clinic, Novosibirsk (protocol VEGA-VCA-2025-014, approved 28 January 2025) and BALTO Veterinary Clinic, Novosibirsk (protocol BALTO-VCB-2025-021, approved 29 January 2025).", "Activator MAF, LLC (Novosibirsk, Russia) supplied Immutalon^TM^ and provided unrestricted financial support.", "Sixty geriatric dogs were randomized (30 EF-M2; 30 placebo) and comprised the intention-to-treat (ITT) population for all efficacy analyses.", "Mean age was 12.4 ± 1.8 y, baseline objective activity averaged 144.8 ± 38.3 min/day, and distributions of sex, neuter status, and symptom flags (pain, pruritus, otitis) were comparable between groups (Table 1)."], "quote_scope": "fulltext"}], "summary": "GERI-VITAL-DOG was a multicenter, randomized, double-blind, placebo-controlled trial at two referral clinics in Novosibirsk, Russia that randomized 60 client-owned geriatric dogs (10 years or older, mean 12.4 years) 1:1 to subcutaneous EF-M2 (Immutalon) at 0.1 ug/kg every 72 h for 4 weeks, with a blinded step-up to every 48 h for partial responders, or matched placebo, followed by 4 weeks off treatment. The co-primary endpoints were accelerometer-measured active minutes per day at week 1 and a day-28 vitality composite. EF-M2 beat placebo on both (+23.05 min/day; +2.01 z-units), with favorable secondaries and owner-reported global improvement of 93.3% vs 10.0% at day 28, and mild infrequent adverse events; the product and unrestricted funding came from Activator MAF, LLC.", "notes": "No trial registration is mentioned; clinic IACUC approvals are dated January 2025 and the protocol version is dated November 2024. The abstract renders the dose as 0.1 μg/kg; the full text uses the micro sign in 1 µg/mL.", "parent_id": null, "tags": ["drug", "immunomodulation", "macrophage", "activity", "vitality", "inflammaging", "client-owned"], "extracted_by": "claude-subagent-batch-C"}
+{"id": "es-msc-and-ev-geriatric-small-dogs-cognition-mobility-pilot-2025", "name": "Human embryonic stem cell-derived MSCs and MSC extracellular vesicles in geriatric small dogs with cognitive and behavioral changes (pilot)", "acronym": null, "kind": "pilot_study", "status": "completed", "setting": "client_owned", "intervention": "Human embryonic stem cell-derived mesenchymal stem cells (ES-MSCs) by a single intravenous injection, or ES-MSC-derived extracellular vesicles (ES-MSC-EVs) by two subcutaneous injections", "intervention_class": "cell_or_gene_therapy", "comparator": "None (two active arms compared; no placebo or untreated group)", "dose_regimen": "ES-MSC: single intravenous injection of 1.0 x 10^7 cells for dogs 3-7 kg or 2.0 x 10^7 cells for dogs 7-12 kg; ES-MSC-EV: 1.0 x 10^10 particles per dog subcutaneously on the first day and 1 week later", "duration": "2 weeks after treatment", "population": {"n": 42, "n_note": "21 ES-MSC and 21 ES-MSC-EV; 43 recruited, 42 participated", "breed": "Maltese and Miniature Poodle most common; mixed small breeds", "age": "11 years or older; median age 14 years (ES-MSC) and 13 years (ES-MSC-EV)", "other": "geriatric small dogs (3 to 12 kg) exhibiting cognitive and behavioral changes; owners willing to participate; treated at three animal hospitals in Seoul, Republic of Korea"}, "primary_outcome": "Canine Cognitive Dysfunction Rating (CCDR) and Liverpool Osteoarthritis in Dogs (LOAD) scores before and 2 weeks after treatment; safety by complete blood count and serum chemistry", "result": "No notable side effects were detected in either group, and the questionnaire survey revealed that both groups showed alleviation in CCDR and LOAD scores following administration.", "lead_organization": "Daewoong Pharmaceutical Co., Ltd., Republic of Korea (cell production and IACUC approval) with Helix Animal Hospital, Korean Animal Cancer Center and Songjeong Animal Medical Center, Seoul", "sponsor_or_funder": "No financial support declared; several authors employed by Daewoong Co., Ltd. and Daewoong Pet, Corp.", "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "pmid", "pmid": "40206251", "slug": null, "doi": "10.3389/fvets.2025.1549870", "title": "Evaluation of cognitive and mobility function in geriatric dogs following treatment with stem cell and stem cell extracellular vesicles derived from embryonic stem cells: a pilot study.", "year": 2025, "role": "results", "quotes": ["Declining physical or mental health in older dogs can lead to changes in the dog's cognitive and musculoskeletal function.", "In the present study, geriatric small dogs exhibiting cognitive and behavioral changes were treated with human embryonic stem cell-derived mesenchymal stemcells (ES-MSCs,", "Before and 2 weeks after treatment, the cognitive and mobility status of the dogs were assessed using theCanine Cognitive Dysfunction Rating (CCDR) and the Liverpool Osteoarthritis in Dogs (LOAD) scale.", "Additionally, safety assessments were conducted through blood tests such as complete blood count and serum chemistry.", "Following an assessment of clinical symptoms and blood tests in both the groups receiving ES-MSC and ES-MSC-EVs treatments, no notable side effects were detected. Moreover, the questionnaire survey revealed that both groups showed alleviation in CCDR and LOAD scores following administration.", "These findings suggest that ES-MSC and ES-MSC-EV treatments have the potential to be used as a therapeutic option for improving clinical symptoms of degenerative diseases such as canine cognitive dysfunction and degenerativemusculoskeletal diseases in elderly dogs."], "quote_scope": "abstract"}, {"type": "pmid", "pmid": "40206251", "slug": null, "doi": "10.3389/fvets.2025.1549870", "title": "Evaluation of cognitive and mobility function in geriatric dogs following treatment with stem cell and stem cell extracellular vesicles derived from embryonic stem cells: a pilot study.", "year": 2025, "role": "design", "quotes": ["Forty-three dogs aged 11 years or older and weighing 3 to 12 kg whose owners were willing to participate in the study were initially recruited into the study.", "Ultimately, 42 dogs participated in this test, and were randomly divided into ES-MSC administration group and ES-MSC-EV administration group.", "This study was conducted at three animal hospitals: Helix Animal Hospital, Korean Animal Cancer Center, and Songjeong Animal Medical Center, all located in Seoul, Republic of Korea.", "Twenty-one dogs in ES-MSC group were injected intravenously with ES-MSCs only once. The dosage per injection was 1.0 × 10^7^ cells for dogs weighing 3–7 kg and 2.0 × 10^7^ cells for dogs weighing 7–12 kg.", "Twenty-one dogs in ES-MSC-EV group received two administrations of ES-MSC-EV, on the first day and 1 week later. ES-MSC-EV was administered via subcutaneous injection. The dosage per injection was 1.0 × 10^10^ particles per dog, regardless of body weight.", "Maltese, Miniature poodles were most common breeds in both groups.", "| Median age, years | 14 | 13 |", "This study was conducted following the protocols approved by the Institutional Animals Care and Use Committee of Daewoong Pharmaceutical, Republic of Korea, and in compliance with the authorized guidelines (Approval number: IACUC-24-047).", "The author(s) declare that no financial support was received for the research and/or publication of this article.", "T-YK, J-AC, H-KO, SY, and JY were employed by Daewoong, Co., Ltd. J-BM and SW were employed by Daewoong Pet, Corp."], "quote_scope": "fulltext"}], "summary": "A pilot study at three animal hospitals in Seoul randomly divided 42 client-owned geriatric small dogs (11 years or older, 3-12 kg, mostly Maltese and Miniature Poodles) with cognitive and behavioral changes into a group given one intravenous dose of human embryonic stem cell-derived mesenchymal stem cells (n = 21) and a group given two subcutaneous doses of ES-MSC extracellular vesicles (n = 21). CCDR and LOAD questionnaire scores and blood safety tests were compared before and 2 weeks after treatment. No notable side effects were seen and both groups showed improved CCDR and LOAD scores; there was no placebo or untreated arm.", "notes": "Two active arms with no control group and only a 2-week follow-up; cells are human ESC-derived and produced by Daewoong Pharmaceutical, whose employees are among the authors.", "parent_id": null, "tags": ["stem-cells", "extracellular-vesicles", "cognition", "mobility", "pilot", "client-owned"], "extracted_by": "claude-subagent-batch-C"}
+{"id": "loyal-loy-001-large-dogs", "name": "LOY-001: IGF-1-lowering long-acting injection for large and giant breed dogs (Loyal)", "acronym": "LOY-001", "kind": "regulatory_program", "status": "ongoing", "setting": null, "intervention": "LOY-001, a prescription long-acting injection that reduces IGF-1 levels", "intervention_class": "drug", "comparator": null, "dose_regimen": "injection administered by a veterinarian every three to six months", "duration": null, "population": {"n": null, "n_note": null, "breed": "large and giant breeds", "age": "7 years and older, weighing at least 40 lb", "other": null}, "primary_outcome": "healthy lifespan extension", "result": null, "lead_organization": "Loyal (San Francisco)", "sponsor_or_funder": "Loyal", "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "web", "pmid": null, "slug": "loyal-for-dog-owners", "doi": null, "title": "Loyal: for dog owners (company page)", "year": 2026, "role": "company", "quotes": ["LOY-001 is a prescription long-acting injection, while LOY-003 is a prescription daily pill.", "LOY-001 is intended for dogs 7 years and older, weighing at least 40 lb, whereas LOY-003 is developed for dogs 5 years and older, weighing at least 60 lb.", "Both drugs target the over-expression of IGF-1, a growth hormone that we believe is associated with large dogs’ shorter lifespan relative to small dogs.", "LOY-001 received a Reasonable Expectation for Effectiveness (RXE) technical section complete letter in 2023"], "quote_scope": "web"}, {"type": "web", "pmid": null, "slug": "gizmodo-loy-001", "doi": null, "title": "Loyal drug LOY-001 to extend lifespan of giant dog breeds (Gizmodo)", "year": 2023, "role": "press", "quotes": ["LOY-001 reduces the levels of IGF-1 in large and giant dog breeds, extending healthy life spans.", "The drug is an injectable that would be administered by a vet every three to six months."], "quote_scope": "web"}], "summary": "LOY-001 is Loyal's long-acting injectable intended to extend healthy lifespan in large and giant breed dogs aged 7 years or older weighing at least 40 lb by lowering IGF-1, given every three to six months. The FDA accepted its reasonable-expectation-of-effectiveness technical section in 2023. No trial design or results have been published.", "notes": "Company- and press-sourced only; trial size, design and results undisclosed as of 2026-10-01.", "parent_id": null, "tags": ["lifespan", "drug", "igf-1", "large-breeds", "fda-conditional-approval", "loyal"], "extracted_by": "claude-hand-curated"}
+{"id": "loyal-loy-003-large-dogs-pill", "name": "LOY-003: IGF-1-lowering daily pill for large breed dogs (Loyal)", "acronym": "LOY-003", "kind": "regulatory_program", "status": "ongoing", "setting": null, "intervention": "LOY-003, a prescription daily pill targeting IGF-1 over-expression", "intervention_class": "drug", "comparator": null, "dose_regimen": "daily oral tablet (dose not disclosed)", "duration": null, "population": {"n": null, "n_note": null, "breed": "large breeds", "age": "5 years and older, weighing at least 60 lb", "other": null}, "primary_outcome": "healthy lifespan extension", "result": null, "lead_organization": "Loyal (San Francisco)", "sponsor_or_funder": "Loyal", "registration": [], "start_year": null, "end_year": null, "sources": [{"type": "web", "pmid": null, "slug": "loyal-for-dog-owners", "doi": null, "title": "Loyal: for dog owners (company page)", "year": 2026, "role": "company", "quotes": ["LOY-001 is a prescription long-acting injection, while LOY-003 is a prescription daily pill.", "LOY-001 is intended for dogs 7 years and older, weighing at least 40 lb, whereas LOY-003 is developed for dogs 5 years and older, weighing at least 60 lb.", "In 2026, LOY-003 completed its RXE section."], "quote_scope": "web"}, {"type": "web", "pmid": null, "slug": "gizmodo-loy-001", "doi": null, "title": "Loyal drug LOY-001 to extend lifespan of giant dog breeds (Gizmodo)", "year": 2023, "role": "press", "quotes": ["Loyal is also developing a pill that would address the same issue, codenamed LOY-003."], "quote_scope": "web"}], "summary": "LOY-003 is Loyal's daily pill counterpart to LOY-001, intended for large breed dogs aged 5 years or older weighing at least 60 lb and targeting IGF-1 over-expression. The company reports that its reasonable-expectation-of-effectiveness section was completed in 2026. No trial design or results have been published.", "notes": "Company- and press-sourced only; developed with Crinetics Pharmaceuticals according to the company; trial details undisclosed as of 2026-10-01.", "parent_id": null, "tags": ["lifespan", "drug", "igf-1", "large-breeds", "fda-conditional-approval", "loyal"], "extracted_by": "claude-hand-curated"}