NCT05835999

Everolimus Aging Study

Clinical Evaluation of mTORC1 Inhibition for Geroprotection

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 106 (estimated)
• Sponsor: University of Wisconsin, Madison · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Accepted

Summary

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 for up to approximately 8 weeks.

Detailed description

Pharmacological inhibition of mechanistic target of rapamycin (mTOR) has been repeatedly demonstrated to extend lifespan and prevent or delay several age-related diseases in diverse model systems. However, the risk of potentially serious side effects in humans have thus far prevented the long-term use of the mTOR inhibitor rapamycin as a therapy for aging and age-related diseases. Therefore, it remains unknown whether rapamycin or rapamycin analogs (rapalogs) can safely improve healthy aging in humans. The objective of this project is to determine if 24 weeks of daily low dose (0.5 mg/day) or weekly intermittent (5 mg/week) treatment with the rapalog everolimus can safely improve physiological and molecular hallmarks of aging in middle-aged to older insulin resistant adults who are at high risk for nearly every age-related condition. 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.

Conditions

• Aging
• Insulin Resistance

Interventions

Type	Name	Description
DRUG	Everolimus 0.5 MG once per day	Everolimus is considered an mTOR kinase inhibitor
DRUG	Everolimus 5 MG once per week	Everolimus is considered an mTOR kinase inhibitor
DRUG	Placebo once per day	No therapeutic effect
DRUG	Placebo once per week	No therapeutic effect

Timeline

• Start date: 2023-03-24
• Primary completion: 2026-09-01
• Completion: 2026-09-01
• First posted: 2023-05-01
• Last updated: 2025-12-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study