This trial was discussed by the principal investigator, Dr. Adam Konopka at the University of Wisconsin, in a presentation to the Transhumanist Party webcast starting around 32:33 here:
This will be by a substantial margin the best human trial of a rapalog for aging in people without overt disease yet launched.
The objective of this project is to determine if mTORC1 inhibition by 24 weeks of daily (0.5 mg/day) or weekly (5 mg/week) everolimus can safely improve physiological and molecular hallmarks of aging in humans. [86] Participants who are 55-80 years old and insulin resistant or prediabetic will be randomized to treatment and can expect to be on study for up to approximately 38 weeks. Participants aged 18-35 will not receive the intervention and can expect to be on study for up to approximately 8 weeks.
The two dose regimens are the same as in the original Joan Mannick trial, which is where everyone got the once-weekly regimen from, with two different placebos to match against the alternative doses. The primary outcome will be insulin and glucose response to an OGTT (using labeled glucose in the dual-tracer method) but they’re going to do a lot of testing of subjects over the course of the trial.
Using a double-blinded, randomized, placebo-controlled clinical trial, the investigators will perform a battery of gold-standard and innovative techniques to test the hypothesis that daily low dose or weekly everolimus treatment will improve 4 inter-related domains of physiological aging: metabolic, cardiac, cognitive, and physical function. The investigators will also assess the incidence of adverse events and changes from baseline blood chemistry, blood cell counts, lipids, glucose, and insulin.
To comprehensively examine the molecular target specificity and the impact on mechanisms of aging by everolimus, the team will evaluate mTORC1 and mTORC2 signaling, assess mitochondrial bioenergetics, and perform a multi-omics approach (epigenomics, transcriptomics, proteomics, lipidomics, and metabolomics) in blood and/or muscle biopsy samples.
|Actual Study Start Date : |March 24, 2023|
|Estimated Study Completion Date : |December 31, 2026|