Currently active phase 2 trial (NCT05835999) directly testing this Atlas's open dosing hypothesis: whether daily low-dose (0.5mg) versus weekly (5mg) everolimus can improve aging biomarkers and insulin resistance in humans without the metabolic penalty seen with continuous higher-dose rapalog use. No results yet - status ACTIVE_NOT_RECRUITING.
| Evidence tier | — Registered trial, no results yet |
| Study type | Registered Trial |
| Model system | Humans, RCT (registered, ongoing) |
| Journal | ClinicalTrials.gov (registration) |
| Year | — |
| Peer reviewed | No |
| Source | DOI NCT05835999 |
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. 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 up to approximately 8 weeks. Pharmacological inhibition of mTOR has repeatedly been shown to extend lifespan and prevent or delay several age-related diseases in diverse model systems, but the risk of serious side effects has prevented long-term use of rapamycin as an anti-aging therapy. Using a double-blinded, randomized, placebo-controlled design, the investigators test the hypothesis that daily low-dose or weekly everolimus improves four inter-related domains of physiological aging (metabolic, cardiac, cognitive and physical function), assess adverse events and blood chemistry, and evaluate mTORC1/mTORC2 signaling, mitochondrial bioenergetics and a multi-omics profile (epigenomics, transcriptomics, proteomics, lipidomics, metabolomics) in blood and/or muscle biopsy. Conditions: Aging, Insulin Resistance. (Registered trial summary; source: ClinicalTrials.gov NCT05835999.)
| Intervention | Everolimus – daily 0.5 mg vs weekly 5 mg, 24 weeks |
| Target | mTORC1 |
| Model | Human – RCT (registered, ongoing; age 55–80, insulin-resistant/prediabetic) |
| Effect | No results yet (ACTIVE_NOT_RECRUITING) – tests whether dosing improves aging hallmarks without metabolic penalty |