mTOR medicines for healthier aging in older adults

Characterization of mTOR Inhibitor Pharmacokinetics and Pharmacodynamics in Older Adults .

This trial will test two mTOR drugs, sirolimus and everolimus, in people 65 and older to measure drug levels and see if they improve biomarkers of aging.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 65 Years to 80 Years
• Sex: All
• Sponsor: University of Texas Southwestern Medical Center (Academic / other)
• Locations: 1 site (Dallas, Texas)
• Trial ID: NCT06727305 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 interventional trial will give older adults short courses of sirolimus or everolimus and collect serial blood samples to define pharmacokinetics and pharmacodynamics in this age group. Researchers will measure a senescence-associated secretory phenotype (SASP) index at baseline and 3 months to see whether those biomarkers shift with treatment. The study also collects exploratory laboratory measures (ESR, CRP, S6K activity, mitochondrial function, metabolomics) and functional tests (walking speed, chair stand, standing balance, grip strength). Results are intended to define safe dosing and biological signals to guide larger trials of mTOR inhibitors for aging-related outcomes.

Who should consider this trial

Good fit: Ideal candidates are community-dwelling adults aged 65 or older who can understand and follow procedures and do not have severe kidney or liver disease, uncontrolled hypertension, recent major cardiovascular or hemorrhagic/thrombotic events, dementia, dependence in basic ADLs, or medications that significantly interact with sirolimus/everolimus.

Not a fit: Patients with creatinine clearance <30 mL/min, chronic liver disease, uncontrolled systolic blood pressure >160 mm Hg, recent CNS hemorrhage or recent thrombotic events without anticoagulation, recent heart failure or myocardial infarction, dementia, dependence in Katz ADLs, or taking drugs that alter sirolimus levels are unlikely to be eligible and may not benefit from participation.

Why it matters

Potential benefit: If successful, the trial could identify safe dosing and show whether mTOR inhibitors alter aging-related biomarkers, laying groundwork for larger studies aimed at slowing functional decline.

How similar studies have performed: Prior animal studies and small human trials have suggested mTOR inhibitors can modify aging pathways and improve immune or metabolic markers, but robust PK/PD and aging-biomarker data in older adults are limited.

Eligibility criteria

Inclusion Criteria:

1. Community-dwelling adults
2. Patients should be 65 Years and older
3. Patients is able to understand and follow trial procedures

Exclusion Criteria:

1. Creatinine clearance \<30 mL/min;
2. History of chronic liver disease;
3. Uncontrolled Hypertension (i.e., systolic blood pressure \>160 mm Hg);
4. Hemorrhagic central nervous system (CNS) event within 1 year from screening visit;
5. Thrombotic event (DVT,PE) within 1 year from screening visit if not on anticoagulation;
6. Planned major surgical procedures;
7. Cardiovascular diseases ( i.e., admission for heart failure or myocardial infarction within 12 months);
8. Taking medication that increase or decrease sirolimus blood concentrations;
9. Other investigational therapy received within 1 month prior to screening visit;
10. History of dementia; 11 Dependence in any Katz Basic Activities of Daily Living.

Where this trial is running

Dallas, Texas

• UT Southwestern Medical Center — Dallas, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Irina Timofte, MD, MS — University of Texas Southwestern Medical Center
• Study coordinator: Irina Timofte, MD, MS

Conditions Aging; Geriatic; Disability