Rapamycin + Everolimus for Aging
(RESTOR Trial)

Recruiting in Palo Alto (17 mi)

Overseen byEllen Kraig, PhD

Age: 65+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Waitlist Available

Sponsor: The University of Texas Health Science Center at San Antonio

Trial Summary

What is the purpose of this trial?

As people get older, there are changes in their cells and tissues that may affect their ability to function. This can lead to increased death and age-associated disorders, like heart disease, cancer, and Alzheimer's disease. Studies in animal models have been able to identify drugs that slow the aging process, leading to a longer, healthier life. This study is focused on one such family of drugs, called mTOR inhibitors, and the investigators' goal is to test two of these drugs, Rapamycin (Sirolimus) and Everolimus (Afinitor), in healthy older adults to find a dose and dose timing that can be used to safely inhibit mTOR to the levels seen in young healthy persons. The investigators expect that the dose that works well in women may differ from the one that is best in men, so it is important to include both sexes in this research.

Eligibility Criteria

This trial is for healthy older adults interested in participating in a study that aims to slow down the aging process. The focus is on finding safe dosages of drugs called mTOR inhibitors, which might help reduce age-related issues. Both men and women are encouraged to join.

Inclusion Criteria

I am part of the older cohort for Sub-study 2 or 3.

I am either a man or a woman.

Fully vaccinated against COVID19

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Exclusion Criteria

I am eligible for the older cohort sub-studies.

I have a chronic inflammatory, autoimmune disease, or an ongoing infection.

Allergic to lidocaine

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Treatment Details

Interventions

Everolimus (mTOR Inhibitor)
Rapamycin (mTOR Inhibitor)

Trial OverviewThe RESTOR trial is testing two mTOR inhibitor drugs, Rapamycin and Everolimus, against a placebo to see if they can safely mimic the cellular conditions of younger individuals in older adults, potentially slowing aging.

Participant Groups

7Treatment groups

Experimental Treatment

Placebo Group

Group I: Aim 2: Sub-study 3 Optimized INTERMITTENT Dosing of an mTOR inhibitorExperimental Treatment2 Interventions

Based on the findings from Aim 1, the optimal drug (RAPA or EVERO), interval between doses, and dose for INTERMITTENT delivery will be tested in a blinded placebo-controlled trial in older human subjects. The drug/dose/interval used in males may differ from the one used in females as the OD will be determined independently for the two sexes. PD parameters 'downstream' from mTOR will be followed. Although drug is delivered on an intermittent schedule, subjects will be given a pill each day (either drug or placebo, as scheduled) to maintain blinding.

Group II: Aim 2: Sub-study 3 Optimized DAILY Dose of an mTOR inhibitorExperimental Treatment2 Interventions

Based on the findings from Aim 1, the optimal drug (RAPA or EVERO) and dose for DAILY delivery will be tested in a blinded placebo-controlled trial in older human subjects. The drug/dose used in males may differ from the one used in females as the OD will be determined independently for the two sexes. PD parameters 'downstream' from mTOR will be followed.

Group III: Aim 1:Sub-study 2 Intermittent dosing Cohort RapamycinExperimental Treatment1 Intervention

Aim 1 is an open label, adaptive, dose finding PK/PD trial in older women and men. In sub-study 2 (part of Aim 1), an older cohort will be studied to determine the optimal dose (OD) in milligrams and the optimal interval for intermittent delivery of rapamycin (RAPA) based on changes in PD parameters 'downstream' from mTOR. Based on the data acquired, additional older cohorts will be tested at higher/lower doses in an adaptive, step-wise trial design.

Group IV: Aim 1:Sub-study 2 Daily dosing Cohort RapamycinExperimental Treatment1 Intervention

Aim 1 is an open label, adaptive, dose finding PK/PD trial in older women and men. In sub-study 2 (part of Aim 1), an older cohort will be studied to determine the optimal dose (OD) in milligrams of rapamycin (RAPA) based on changes in PD parameters 'downstream' from mTOR. Based on the data acquired, additional older cohorts will be tested at higher/lower doses in an adaptive, step-wise trial design.

Group V: Aim 1: Sub-study 2 Intermittent dosing Cohort EverolimusExperimental Treatment1 Intervention

Aim 1 is an open label, adaptive, dose finding PK/PD trial in older women and men. In sub-study 2 (part of Aim 1), an older cohort will be studied to determine the optimal dose (OD) in milligrams and the optimal interval for intermittent delivery of everolimus (EVERO) based on changes in PD parameters 'downstream' from mTOR. Based on the data acquired, additional older cohorts will be tested at higher/lower doses in an adaptive, step-wise trial design.

Group VI: Aim 1: Sub-study 2 Daily dosing Cohort EverolimusExperimental Treatment1 Intervention

Aim 1 is an open label, adaptive, dose finding PK/PD trial in older women and men. In sub-study 2 (part of Aim 1), an older cohort will be studied to determine the optimal dose (OD) of everolimus (EVERO) in milligrams based on changes in PD parameters 'downstream' from mTOR. Based on the data acquired, additional older cohorts will be tested at higher/lower doses in an adaptive, step-wise trial design.

Group VII: Aim 2: Sub-study 3 Placebo controlPlacebo Group1 Intervention

Daily administration of a placebo will be given to a cohort of older human subjects. Both males and females will be enrolled as controls.

Everolimus is already approved in United States, European Union, United States for the following indications:

🇺🇸 Approved in United States as Afinitor for: