Do you weigh more than 40lbs, have extensive body hair and enjoy outdoor recreation? If so, this new rapamycin trial could be for you.
Calling all dog owners! A clinical trial is currently underway across the United States, seeking to assess the effects of rapamycin on health and aging in dogs. The Test of Rapamycin in Aging Dogs (TRIAD) aims to conclusively show whether the drug, an mTOR inhibitor that has been shown to increase lifespan in mice, has a similar effect in dogs.
While the study also aims to learn if rapamycin improves heart health, mobility and cognitive function, its primary goal is to determine its effect on lifespan – leading some to dub it the first “true” clinical trial for longevity.
Longevity.Technology: TRIAD is part of the Dog Aging Project, a research initiative co-founded by former University of Washington professor Matt Kaeberlein. Having recently left academia to focus on other opportunities (more on those another day), Kaeberlein is taking a step back from the day-to-day running of TRIAD. To find out more about the trial and its objectives, we caught up with Kaeberlein and May Reed, a professor in geriatric medicine at the University of Washington, and one of the new academic leads for TRIAD.
TRIAD has been enrolling dogs for around a year now, but progress has been slower than the organizers had hoped. One of the challenges is that the dogs need to be seen in specific centers, so much of the focus has been on opening new sites around the country.
“We’re up to around 20 sites now – all across the United States,” says Reed. “And we have over 100 dogs enrolled. Things are picking up – we’ve demonstrated that this type of trial can get launched, so now we need to get the word out and get more dogs enrolled!”
To help accelerate enrollment in TRIAD, the team has developed a “fast track” option, a rapid assessment form to allow owners to check the potential suitability of their dogs for participation in the study. Check it out here.
There is, of course, no guarantee that your dog is going to be given rapamycin in the trial, and Kaeberlein says it would be “unethical” to tell owners that their dog is likely to benefit from being in TRIAD.
“However, if there is even a chance that we can give people’s pets 20%, 30% or 40% longer, healthier lives, then this has to happen – and I think that that will motivate a lot of people,” he says. “I think that it is very likely that this trial, or one in the future, will play a fundamentally important role in increasing the healthy longevity of not just your dog, but your future dogs and the future dogs, and potentially cats and other companion animals, for lots and lots of other people. And I hope that will resonate with other people who also consider their pets to be part of their family.”
What is rapamycin?
Rapamycin, originally developed as an immunosuppressant for organ transplant patients, has become the subject of keen interest in aging and longevity research due to numerous positive lifespan and healthspan studies in research labs around the world.
“There’s a huge body of literature in laboratory animals, supporting the idea that rapamycin is a very effective drug for targeting the biology of aging in a way that seems to either slow or, in some cases, even reverse functional declines that go along with aging, reduce disease incidence and delay mortality,” says Kaeberlein. “And that seems to be true in every laboratory animal where this has been studied.”
Results to date have been particularly impressive in mice, especially when it comes to reversing the effects of aging, which is what convinced Kaeberlein to start looking at the drug’s effect in dogs in the first place.
“It occurred to me that there was a real opportunity to potentially have a positive, meaningful impact on healthspan and lifespan in people’s pets using something like rapamycin and the geroscience approach,” he says. “About 10 years ago, I became convinced that some of these geroscience interventions that work in mice, will also work in dogs – I have no doubt about that. I don’t know if it’ll be percentagewise the same, but the biology is so shared that there is no way I can imagine it not happening. And rapamycin is our best shot on goal right now.”
Is rapamycin safe for my dog?
The Dog Aging Project has already carried out two small rapamycin studies in dogs, predominantly to demonstrate that the drug was safe.
“A study of a geroscience intervention in companion animals has many parallels with a paediatric study in humans,” says Kaeberlein. “Safety is always important but in this case it’s really important. Many people think of their pets as being like their children, so you have to think about it that way.”
While the initial trials did seem to show some efficacy benefits, the small number of dogs studied mean that the results can’t be considered statistically significant.
“We knew we weren’t powered to show efficacy in those trials, but TRIAD is different,” says Kaeberlein. “What we want to know is, can we find evidence that rapamycin has an impact on lifespan and potentially healthspan metrics, in a large, double-blind, randomized, multi-site, veterinary, placebo-controlled clinical trial?”
All those adjectives are important to Kaeberlein, because he is stressing that TRIAD is being held to the highest possible standards.
“As best we can, we’re using the same sort of quality standards that you would use in a similar human clinical trial,” he says. “But the one big difference here is this is a study of normative aging. It’s not a disease trial – these are healthy, older dogs. Can rapamycin have a positive impact going forward on how long they maintain that healthy status and how long they live? Lifespan is the primary endpoint, and that’s what we’re statistically powered to see.”
Powered to detect lifespan changes
The “statistical power” the TRIAD study is aiming for is also one of its biggest challenges – the number of dogs needed. The original study design was for 350 dogs, which Kaeberlein says would have been sufficient to detect around a 20% change in lifespan. But an encounter with Peter Attia changed everything.
“I told Peter what the study design was and why it was that size, and he made the point that the lifespan effect from rapamycin in the first mouse study was 9% to 14%,” recalls Kaeberlein. “I said we didn’t have the money to do that, so he said he’d get us the money. And he did.”
Attia assembled a group of donors, including lifestyle guru Tim Ferris, who provided a “couple of million” dollars to allow the expansion of TRIAD to its current goal of 580 dogs.
“The study involves a one-year treatment period with a two-year follow up,” says Kaeberlein. “To be able to model mortality effectively in a dog population, we calculated that the dogs should be at least seven years old, and weigh between 40 and 110 pounds. And the model said that we needed 580 dogs over a three-year period to detect a 9% change in lifespan.”
Potential for human longevity studies?
Reed, a physician and geriatrician with 35 years’ experience in the laboratory has worked on everything from caloric restriction to growth factors and is clearly excited about the potential to learn from TRIAD project.
“There is such a clear correlation in dogs with the syndromes that older people develop, whether you want to call it aging, or diseases associated with aging,” she says. “It’s just so uncanny – everything from the musculoskeletal system to the cognitive issues, it’s just not something you can recapitulate in the laboratory – you can’t reproduce it in mice or rats.”
So, what might be the human implications of positive lifespan results in the dogs in the TRIAD study?
“It wouldn’t prove anything about the potential effects of rapamycin in humans,” says Kaeberlein. “But I think there could be a pretty big impact from a clear win on the veterinary side in the way that the regulators at the FDA think about this for regulation of human geroscience interventions.”