Researchers at the University of Arizona R. Ken Coit College of Pharmacy will begin a double-blind, randomized Phase 3 clinical trial this year to evaluate whether a drug used to prevent organ transplant rejection can also improve older adults’ resilience and immune function.
The clinical trial with the drug, rapamycin, is funded with $12 million in philanthropic support from alumnus R. Ken Coit. Coit graduated from the College of Pharmacy in 1967 and has been a supporter of the college for decades. In 2021, his $50 million naming gift commitment was used to establish endowed faculty positions and student scholarships and to renovate the Coit History of Pharmacy and Health Sciences Museum.
“Ken’s generosity is making possible the first investigator-led clinical trial in the College of Pharmacy,” said Brian Erstad, interim dean of the Coit College of Pharmacy. “His latest gift will enable new opportunities for our researchers to continue to gain further insights into the human lifespan and make new inroads in the development of therapeutics to slow aging.”
“Rapamycin is our best shot on goal for improving resiliency and healthspan as we age,” Coit said. “Several studies have proven that rapamycin can improve vaccine efficacy and improve oral health in older adults. This study will measure the ability for low-dose rapamycin to maintain or improve physical and immunologic functioning in people 65 years and older.”
According to lead investigator Bonnie LaFleur, a professor in the Coit College of Pharmacy, the Phase 3 clinical trial, if it receives final approval from the FDA as expected, is projected to take six years. Participants will be randomized to rapamycin or a placebo that they will take for two years, with an additional year of follow-up. Collaborators will conduct several ancillary studies in parallel with the clinical trial, all with the goal of improving health and well-being in older adults.
Researchers will focus on two main ways to measure the potential effects of rapamycin. The first will gauge the impact of the treatment on physical function, specifically, whether rapamycin changes the transition to frailty, which can significantly impact quality of life. The second will evaluate the levels of an inflammatory marker called IL-6, a measure of inflammation associated with many age-related diseases, including frailty. The researchers want to see if rapamycin can reduce IL-6 levels in the blood.
This is wonderful news. Some credit goes to the decades of work by Andrew Weil creating awareness and acceptance for this kind of work in the medical school. Beyond Arizona, Weil has been a driving force behind the adoption of alternative and geroprotective concepts in medical practice nationwide. I can still recall the shock on a largely MD audience’s face perhaps 30 years ago when unpacked the immune stimulating properties of different classes of mushrooms. Heresy!
Yes. The endpoints seem potentially anemic. The first endpoint mentioned here could be a summary of a family of specific metrics but the second endpoint – Il-6 – perhaps seems narrow to a fault but it does convey that the choice of IL-6 as an endpoint rather than something like p-S6 phosphorylation (a direct readout of mTORC1 inhibition) or epigenetic clocks suggests the investigators are framing this firmly within the geroscience/inflammaging paradigm rather than trying to prove mTOR pathway engagement per se.
LaFleur’s expertise is in immunobiology, oncology, aging, and statistical methods for precision healthcare and biomarkers. She has extensive experience in biomarker-driven and interventional clinical trials, including regulatory submissions for FDA and EMA approved diagnostic tests. She has co-PI connections with Janko Nikolich-Zugich, a highly regarded immunologist at Arizona who has published extensively on immunosenescence. This suggests the immunological endpoints may be considerably more sophisticated than just IL-6 – the “ancillary studies” likely include deeper immune phenotyping. Perhaps this is where the unspecified ancillary studies come into play. The six year time suggests staging and rigor. The modest budget suggests a population of 200-400 across all arms. Good enough to get attention.
I sent an email to a person who is likely my last contact at the medical school, hoping she is not retired. From the press information, it appears that the IND application is still pending or in late-stage review. As a consequence, the trial does not yet appear on ClinicalTrials.gov and no NCT number assigned to it. ClinicalTrials.gov registration is required within 21 days of first patient enrollment so that could be awhile. The school has strong successful relationships with the FDA so approval is likely pro forma.
Wow - 6-years. As Blagosklonny shared: “If you wait until you are ready, it is almost certainly too late.” By Seth Godin
Waiting until you feel “ready” or until everything is perfect is a trap; it often means you have waited too long. Starting immediately—even without full preparation—is essential because you get ready by starting, not by waiting. Delaying action leads to missed opportunities, as you cannot predict when the right moment will pass.
I’ve already been on rapamycin almost 5-years. Glad I was an early adopter.
The PEARL study used questionnaires to evaluate outcomes. One they identified was a decrease in pain among women (WOMAC score often used to evaluate OA pain). Their n of cases and dosage were too small to get statistically meaningful results, nor did they assess for causes of pain. I had quite painful OA. I proposed an n of one experiment to my PCP—14 weeks of 5 mg/week of sirolimus that included a month of titrating up from 1 mg/week. She examined my hands before and after. We were both astounded by the improvement in pain and some in flexibility in my case. Something like this is easily measurable and since there are currently no meaningful treatments for OA it would be a real success story if it was efficacious in a substantial fraction of OA patients. I may have been in the sweet spot to see effects. Enough hand OA to be in real pain, but not enough joint damage to make improvement unlikely. Collectively could we quickly make some suggestions like this to the research team at Arizona based on our various positive experiences for fairly common afflictions?
Great to see. And this is what I’ve been hoping for for a long time - that some wealthy person would donate a chunk of money to run a proper study. No conflicts of interest. No weird proprietary mTOR inhibitors. Just (hopefully) some good honest science, and definitive answers.
I participated in the Pearl trial. I was on very low dose or 10MG compounded formula which later was raised to 15 MB compounded. When my bloodwork failed to show much if any in my system, I was raised to 20MG compounded formula. I was told a 15 MG was equivalent to 3 to 5 MG of regular rapamycin. So for much of that time I wasn’t getting even a normal or 6MG weekly dose. One thing I did notice about the time I started the trial, I was diagnosed with Osteoporosis on my left shoulder. However since being on Rapamycin, My shoulder doesn’t bother me at all. I workout at Planet fitness doing different exercises that require use of shoulders like bench presses and pulldowns etc. So maybe the Rapamycin is responsible for curing my shoulder problems. I recently started GSH and NAD+ home injections. A month on GSH and just over a week on the NAD+. Not cheap but wanted to give both a try.
