Wednesday, May 7, 2025
5/7/2025
Test of Rapamycin in Aging Dogs (TRIAD) - SUMMARY Rapamycin is one of the most promising geroprotective agents identified to date, with proven ability to enhance longevity and improve health in laboratory animals and promising outcomes from more limited human studies. Originally embedded within the Dog Aging Project (DAP), the Test of Rapamycin in Aging Dogs (TRIAD) is a clinical trial for longevity and healthspan metrics in non-diseased, normatively aging companion dogs. With 150 dogs already enrolled, TRIAD will engage a further 430 companion dogs to complete study objectives. Notable for this proposal: 1) the infrastructure and all necessary protocols are in place and approved; 2) the rapamycin formulation is purchased and being utilized; and 3) enrollment, randomization, and clinical evaluation have already begun in over 20 clinical sites, attesting to the feasibility and efficacy of study implementation. The following Specific Aims are proposed: Aim 1. Conduct a randomized, double-blind, placebo-controlled veterinary clinical trial to determine whether once-weekly rapamycin treatment increases lifespan and decreases disease onset in companion dogs. Aim 1 tests if rapamycin treatment initiated in older, moderate to large dogs will a) increase lifespan and b) maintain health in 580 companion dogs. The treatment group will receive 0.15 mg/kg rapamycin once each week for 1 year with 2 years follow-up (total TRIAD duration 3 years). Exams, surveys, and samples will be collected throughout. The impact of rapamycin on lifespan and age-related disease incidence, including: cancers, infectious diseases, immune health, sensory loss, chronic kidney disease, joint disease, and cognitive decline, will be measured. Aim 2. Determine the effects of rapamycin on parameters of function and health in companion dogs. Aim 2 tests the hypothesis that rapamycin improves a) physical (all dogs); b) neurologic (290 dogs); and c) cardiovascular (290 dogs) function. Dogs will be enrolled and monitored in specialty clinics attended by board- certified veterinary cardiologists or neurologists. All parameters will be collected every 6 months for the 3-year duration of TRIAD. Assessments include physical function and frailty, neurologic function, cognition, markers of Alzheimer’s-like pathology, blood pressure, electrocardiogram, and cardiac function. TRIAD will determine whether rapamycin increases lifespan and improves healthspan in aging companion dogs who live with humans and demonstrate many conditions relevant to older adults. Protocols and pipelines for data acquisition, harmonization, and integration are established. There is uniformity and consistency in measures across all sites. Adverse events can be rapidly detected and addressed. TRIAD is a pseudo-pragmatic design that engages publicly accessible health care, data extraction from private records, and involves dogs in their homes. TRIAD will have an outsized impact on geroscience as it will create a foundation for future clinical trial design, recruitment strategies, logistic implementation, data analysis, and integration.
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