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

Abstract

Companion dogs are a powerful model for aging research given their morphologic and genetic variability, risk for age-related disease, and habitation of the human environment. In addition, the shorter life expectancy of dogs compared to human beings provides a unique opportunity for an accelerated timeline to test interventions that might extend healthy lifespan. 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.

Keywords: Canine; Healthspan; Life span; Lifespan; Longevity; Rapamycin.

Fig. 1

General design of the Test of Rapamycin In Aging Dogs randomized clinical trial. Dogs enrolled in the Dog Aging Project (“DAP Pack”) are automatically considered for participation; alternatively, owners of dogs not enrolled in the DAP who are preferentially interested in TRIAD can complete a TRIAD eligibility pre-screening questionnaire if they wish to ascertain likely eligibility before joining the DAP. In either case, dogs must be enrolled in the DAP prior to formal eligibility assessment.