RESTOR: PK/PD mTORi Inhibition in Older Adults
RESTOR [Rapamycin and Everolimus Study Towards Older Rejuvenation]: An Exploratory PK/PD Study of mTOR Inhibition in Older Human Subjects
The University of Texas Health Science Center at San Antonio
194 participants
Aug 13, 2025
INTERVENTIONAL
Conditions
Summary
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
Inclusion Criteria7
- Older Cohort Sub-study 2 (AIM 1) and Sub-study 3 (AIM 2):
- Age ≥65 to 90 years
- Men and women
- In good health with all medical problems stable.
- Community-dwelling
- Agreement to adhere to Lifestyle Considerations throughout study duration.
- Ability of participant to understand and the willingness to sign a written informed consent document.
Exclusion Criteria29
- Older Cohort Sub-study 2 (AIM 1) and Sub-study 3 (AIM 2):
- Resident of nursing home or long-term care facility
- Subjects with diabetes or currently taking glucose lowering medications
- History of moderate-severe heart disease (New York Heart Classification greater than grade II) or pulmonary disease (dyspnea on exertion upon climbing one flight of stairs or less; abnormal breath sounds on auscultation); Moderate to severe valvular heart disease
- Active cancer or history of cancer treatment within the last 5 years
- Chronic inflammatory condition, autoimmune disease, or infectious processes (e.g., active tuberculosis, HIV, rheumatoid arthritis, systemic lupus erythematosus, acute or chronic hepatitis B or C)
- History of a coagulopathy or any medical condition requiring anticoagulation (except low dose ASA)
- Renal insufficiency with an estimated glomerular filtration rate of <30ml/min
- Uncontrolled hypercholesterolemia >350mg/dl or uncontrolled hypertriglyceridemia >500mg/dl
- Anemia or abnormal blood cell counts: hemoglobin level <9.0g.dl; white blood count <3500/mm3; neutrophil count <2000/ mm3; platelet count <125,000/mm3
- History of skin ulcers or poor wound healing
- Active tobacco use (within 6 months)
- Diagnosis of any disabling neurologic disease such as Parkinson's Disease, Amyotrophic Lateral Sclerosis, multiple sclerosis, cerebrovascular accident with residual deficits (muscle weakness or gait disorder), severe neuropathy, diagnosis of dementia or Clox1 score less than 10 at the time of screening visit, cognitive impairment due to any reason such that the patient is unable to provide informed consent
- Liver disease
- Systemic treatment with an immunosuppressant (prednisone, etc.) within the year prior to enrollment
- Treatment with drugs known to affect cytochrome P450 (CYP3A4), i.e., diltiazem, erythromycin.
- Patients with history of recent (within 6 months) myocardial infarction or active coronary disease
- Patients with history of recent (within 6 months) intestinal disorders
- History of severe head trauma, brain injury, brain surgery, inflammation of the brain, or history of seizure disorder
- History of Long-Covid (PASC) within one year
- Acute Covid19 or Covid19 infection within the last 6 months
- Unwilling to forgo grapefruit juice consumption.
- Participation in mTORi study within the prior year. (Note: participants in AIM 1 will be excluded from participating in AIM 2 of the proposed trial.)
- Allergic to RAPA or EVERO
- Allergic to lidocaine
- Recreational drug use
- Donated blood over a two-month period prior to study initiation.
- Currently using cannabidiol (CBD) or tetrahydrocannabinol (THC) or any preparation contained these, or related, substances.
- Currently using hormone replacement or modulating therapies.
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Interventions
mTOR inhibitor
mTOR inhibitor
Inert placebo for rapamycin or everolimus
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06658093