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

Amanda E Coleman^#¹, Kate E Creevy^#², Rozalyn Anderson^{3

4}, May J Reed⁵, Virginia R Fajt⁶, Kathleen M Aicher², Genna Atiee², Brian G Barnett², Ryan D Baumwart⁷, Beth Boudreau², Suzanne M Cunningham⁸, Matthew D Dunbar⁹, Bobbie Ditzler², Anna M Ferguson¹⁰, Kiersten K Forsyth², Anya N Gambino¹⁰, Sonya G Gordon², Hillary K Hammond¹¹, Sydney N Holland², Mary K Iannaccone¹⁰, Kate Illing², Saki Kadotani¹², Shelby A Knowles¹⁰, Evan L MacLean¹³, Brian A Maran¹⁴, Lauren E Markovic¹¹, Stephanie McGrath¹⁵, Rachel L Melvin¹⁰, Mikaela S Mueller¹⁴, O Lynne Nelson⁷, Natasha J Olby¹⁶, Theresa E Pancotto¹⁷, Elizabeth Parsley⁸, Brianna M Potter¹⁵, Jena O Prescott², Ashley B Saunders², Holly M Sawyer¹⁴, Brian A Scansen¹⁵, Sarah M Schmid², Courtney C Smith¹⁸, Sonja S Tjostheim¹⁹, M Katherine Tolbert², Melissa A Tropf²⁰, Lance C Visser¹⁵, Jessica L Ward²⁰, Sonya R Wesselowski², Rebecca C Windsor²¹, Vicky K Yang⁸, Audrey Ruple²², Daniel E L Promislow²³, Matt Kaeberlein^{10

24}; Dog Aging Project Consortium

Collaborators, Affiliations

Affiliations

¹ Department of Small Animal Medicine and Surgery, University of Georgia, Athens, GA, USA. mericksn@uga.edu.
² Department of Small Animal Clinical Sciences, Texas A&M University, College Station, TX, USA.
³ Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
⁴ GRECC William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
⁵ Department of Medicine, University of Washington, Seattle, WA, USA.
⁶ Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
⁷ Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA, USA.
⁸ Department of Clinical Sciences, Tufts University, North Grafton, MA, USA.
⁹ Center for Studies in Demography and Ecology, University of Washington, Seattle, WA, USA.
¹⁰ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
¹¹ Department of Small Animal Medicine and Surgery, University of Georgia, Athens, GA, USA.
¹² Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL, USA.
¹³ College of Veterinary Medicine, University of Arizona, Tucson, AZ, USA.
¹⁴ Olympic Veterinary Cardiology, Everett, WA, USA.
¹⁵ Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA.
¹⁶ Department of Clinical Sciences, North Carolina State University, Raleigh, NC, USA.
¹⁷ Specialists in Companion Animal Neurology, Naples, FL, USA.
¹⁸ Chesapeake Veterinary Cardiology Associates, Lawndale, CA, USA.
¹⁹ Department of Medical Sciences, University of Wisconsin, Madison, WI, USA.
²⁰ Department of Veterinary Clinical Sciences, Iowa State University, Ames, IA, USA.
²¹ Wheat Ridge Animal Hospital, Wheat Ridge, CO, USA.
²² Department of Population and Health Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
²³ Jean Mayer USDA Human Nutrition Research Center On Aging, Tufts University, Boston, MA, USA.
²⁴ Optispan, Inc, Seattle, WA, USA.

^# Contributed equally.

PMID: 39951177
PMCID: PMC12181551
DOI: 10.1007/s11357-024-01484-7

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

Amanda E Coleman et al. Geroscience. 2025 Jun.

. 2025 Jun;47(3):2851-2877.

doi: 10.1007/s11357-024-01484-7. Epub 2025 Feb 14.

Authors

Affiliations

¹ Department of Small Animal Medicine and Surgery, University of Georgia, Athens, GA, USA. mericksn@uga.edu.
² Department of Small Animal Clinical Sciences, Texas A&M University, College Station, TX, USA.
³ Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
⁴ GRECC William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
⁵ Department of Medicine, University of Washington, Seattle, WA, USA.
⁶ Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
⁷ Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA, USA.
⁸ Department of Clinical Sciences, Tufts University, North Grafton, MA, USA.
⁹ Center for Studies in Demography and Ecology, University of Washington, Seattle, WA, USA.
¹⁰ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
¹¹ Department of Small Animal Medicine and Surgery, University of Georgia, Athens, GA, USA.
¹² Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL, USA.
¹³ College of Veterinary Medicine, University of Arizona, Tucson, AZ, USA.
¹⁴ Olympic Veterinary Cardiology, Everett, WA, USA.
¹⁵ Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA.
¹⁶ Department of Clinical Sciences, North Carolina State University, Raleigh, NC, USA.
¹⁷ Specialists in Companion Animal Neurology, Naples, FL, USA.
¹⁸ Chesapeake Veterinary Cardiology Associates, Lawndale, CA, USA.
¹⁹ Department of Medical Sciences, University of Wisconsin, Madison, WI, USA.
²⁰ Department of Veterinary Clinical Sciences, Iowa State University, Ames, IA, USA.
²¹ Wheat Ridge Animal Hospital, Wheat Ridge, CO, USA.
²² Department of Population and Health Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
²³ Jean Mayer USDA Human Nutrition Research Center On Aging, Tufts University, Boston, MA, USA.
²⁴ Optispan, Inc, Seattle, WA, USA.

^# Contributed equally.

PMID: 39951177
PMCID: PMC12181551
DOI: 10.1007/s11357-024-01484-7

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.

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Conflict of interest statement

Declarations. IACUC approval declaration: The University of Washington IRB deemed that recruitment of dog owners for the Dog Aging Project and the administration and content of the DAP surveys are human subjects research that qualifies for category 2 exempt status (IRB ID no. 5988, effective 10/30/2018). All study-related procedures involving privately owned dogs were approved by the Texas A&M University IACUC, under animal use protocols 2021-0317 CAM (effective 12/8/2021 to present) and 2018-0368 CA (effective 12/19/2018 to 12/18/2021). Conflict of interest: The authors declare the following conflicts of interest: MK is a scientific advisor for TriviumVet; DELP is a consultant for WndrHLTH. Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Figures

**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.

See this image and copyright information in PMC

References

1. Horvath S, Lu AT, Haghani A, Zoller JA, Li CZ, Lim AR, et al. DNA methylation clocks for dogs and humans. Proc Natl Acad Sci USA. 2022;119(21):e2120887119. - PMC - PubMed
1. Creevy KE, Austad SN, Hoffman JM, O’Neill DG, Promislow DE. The companion dog as a model for the longevity dividend. Cold Spring Harb Perspect Med. 2016;6(1):a026633. - PMC - PubMed
1. Kaeberlein M, Creevy KE, Promislow DE. The dog aging project: translational geroscience in companion animals. Mammalian genome: official journal of the International Mammalian Genome Society. 2016;27(7–8):279–88. - PMC - PubMed
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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

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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

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