NCT05949658

Rapalog Pharmacology (RAP PAC) Study

Safer mTOR Inhibition for Human Geroprotection

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 72 (estimated)
• Sponsor: University of Wisconsin, Madison · Academic / Other
• Sex: All
• Age: 55 Years – 89 Years
• Healthy volunteers: Accepted

Summary

The objective of RAP PAC is to identify safe and effective weekly dose(s) for the mTOR inhibitors sirolimus and everolimus that intervene on the underlying fundamental biology of aging. Participants who are 55-89 years old that are free of overt chronic diseases will be assigned to either 6 weeks of sirolimus or everolimus (5 mg, 10 mg, or 15 mg once per week). The investigators will complete the everolimus arm first and then subsequently complete the sirolimus arm of the study. Total time on study would be up to 17 weeks to complete baseline and follow up visits.

Detailed description

The mTOR inhibitor rapamycin and rapamycin analogs (rapalogs) extend healthspan and/or lifespan in multiple model systems. However, the risk of adverse events and dose limiting toxicities in humans have thus far precluded the long-term prophylactic use of mTOR inhibitors as a therapy for aging and age-related diseases. The pharmacokinetics and pharmacodynamics (PK/PD) data for mTOR inhibitors in older adults is currently unknown and has prevented the identification of a safe dosage that could maximize health-span extension and minimize adverse effects. RAP PAC will identify a recommended phase 2 trial dose for sirolimus and everolimus in older men and women by performing a phase 1, dose finding study that evaluates PK/PD, safety and tolerability, and mTOR signaling using conventional as well as novel approaches. Overall, the investigators will pair comprehensive molecular and pharmacologic approaches to evaluate PK/PD in humans and identify dosing regimens that safely inhibit mTOR complex 1 (mTORC1) to intervene in the biology of aging.

Conditions

• Aging

Interventions

Type	Name	Description
DRUG	Sirolimus	5mg, 10mg, or 15mg once weekly sirolimus
DRUG	Everolimus	5mg, 10mg, or 15mg once weekly everolimus

Timeline

• Start date: 2024-05-15
• Primary completion: 2027-03-01
• Completion: 2028-12-01
• First posted: 2023-07-18
• Last updated: 2026-02-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study