Safer mTOR Inhibition for Human Geroprotection
University of Wisconsin, Madison
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.
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 phas…
Eligibility
- Age range
- 55–89 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * Middle-age adults free of overt chronic disease * Willing to provide informed consent * Willing to comply with all study procedures and be available for the duration of the study * Able to use and be contacted by telephone * Ability to take oral medication * Not planning to change diet or physical activity status * Adequate organ function as indicated by standard laboratory tests: hematology (complete blood count), and clinical chemistry * Males must agree to avoid impregnation of women during and for four weeks after completing study visits through use of an acceptable…
Interventions
- DrugSirolimus
5mg, 10mg, or 15mg once weekly sirolimus
- DrugEverolimus
5mg, 10mg, or 15mg once weekly everolimus
Location
- University of WisconsinMadison, Wisconsin