Recruiting
Phase 1
Phase 2

mTOR Inhibitors

Sponsor:

University of Texas Southwestern Medical Center

Code:

NCT06727305

Conditions

Aging

Eligibility Criteria

Sex: All

Age: 65 - 70+

Healthy Volunteers: Accepted

Interventions

Sirolimus 0.5 Mg Oral Tablet

Sirolimus 1Mg Oral Tablet

Sirolimus 2 MG Oral Tablet

Everolimus 0.5 MG Oral Tablet

Everolimus 1 MG Oral Tablet

Study Details

Brief summary:

Over the past decades, healthcare systems face significant challenges to meet the needs of an aging population due to progressive debility, functional decline and chronic diseases development. While there is a growing appreciation of the potential impact of mTOR inhibitors on slowing aging processes, preventing chronic disease and prolonging healthy lifespan, a major challenge in developing clinical trials to establish the clinical efficacy of mTOR inhibitors is the absence of pharmacokinetics (PK) and pharmacodynamics (PD) data in older adults. The proposed study will provide the foundation for future clinical trials assessing the role of mTOR inhibitors on aging related indications

Conditions

Aging

Study ID

NCT06727305

Start date

May 11, 2026

Status verified date

Jun, 2026

Completion date

Nov 13, 2027

Anticipated

Primary completion date

Sep 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 65 - 70+

Healthy Volunteers: Accepted

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.

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Prevention

Interventions and Outcome Measures

Arms

active comparator: sirolimus 0.5 mg Arm

Participant would receive 0.5 mg of sirolimus.

active comparator: sirolimus 1 mg Arm

Participant would receive 1 mg of sirolimus.

active comparator: sirolimus 2 mg Arm

Participant would receive 2 mg of sirolimus.

active comparator: everolimus 0.5 mg Arm

Participant would receive 0.5 mg of Everolimus.

active comparator: everolimus 1 mg Arm

Participant would receive 1 mg of Everolimus.

active comparator: everolimus 2 mg Arm

Participant would receive 2 mg of Everolimus.

Interventions

Sirolimus 0.5 Mg Oral Tablet

Sirolimus 0.5 mg oral tablets daily for 2 weeks and complete PK/PD testing. After the first 2 weeks, dose increase, or dose reduction will be made to obtain a stable blood level of 5-7 ng/ml.

Sirolimus 1Mg Oral Tablet

Sirolimus 1 mg oral tablets daily for 2 weeks and complete PK/PD testing. After the first 2 weeks, dose increase, or dose reduction will be made to obtain a stable blood level of 5-7 ng/ml.

Sirolimus 2 MG Oral Tablet

Sirolimus 2 mg oral tablets daily for 2 weeks and complete PK/PD testing. After the first 2 weeks, dose increase, or dose reduction will be made to obtain a stable blood level of 5-7 ng/ml.

Everolimus 0.5 MG Oral Tablet

Everolimus 0.5 mg oral tablets daily for 2 weeks and complete PK/PD testing. After the first 2 weeks, dose increase, or dose reduction will be made to obtain a stable blood level of 5-7 ng/ml.

Everolimus 1 MG Oral Tablet

Everolimus 1 mg oral tablets daily for 2 weeks and complete PK/PD testing. After the first 2 weeks, dose increase, or dose reduction will be made to obtain a stable blood level of 5-7 ng/ml.

Everolimus 2 MG Oral Tablet

Everolimus 2 mg oral tablets for daily for 2 weeks and complete PK/PD testing. After the first 2 weeks, dose increase, or dose reduction will be made to obtain a stable blood level of 5-7 ng/ml.

Primary outcome measure

  • Cmax for Sirolimus [ Time Frame: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24-hour post dose ]
  • Cmax for Everolimus [ Time Frame: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 12-hour post dose ]
  • Ctrough for Sirolimus [ Time Frame: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24-hour post dose ]
  • Ctrough for Everolimus [ Time Frame: Predose (0 hour) on Day 14 and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 12-hour post dose ]
  • AUC for Sirolimus [ Time Frame: Predose (0 hour) on Day 14 and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24-hour post dose ]
  • AUC for Everolimus [ Time Frame: Predose (0 hour) on Day 14 and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 12-hour post dose ]
  • CL/F for Sirolimus [ Time Frame: Predose (0 hour) on Day 14 and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24-hour post dose ]
  • CL/F for for Everolimus [ Time Frame: Predose (0 hour) on Day 14 and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 12-hour post dose ]
  • S6K Activity, in Sirolimus cohorts [ Time Frame: Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24-hour post dose on Day 1 and Day 14 ]
  • S6K Activity, in Everolimus cohorts [ Time Frame: Predose (0 hour) on Day 14 and 0.5, 1, 1.5, 2.5, 3, 4, 6, and 12-hour post dose on Day 1 and Day 14 ]
  • Senescence-associated secretory phenotype (SASP) index [ Time Frame: Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13 ]
  • Erythrocyte sedimentation rate (ESR) [ Time Frame: Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13 ]
  • C-reactive protein (CRP) [ Time Frame: Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13 ]
  • 6-minute walk test (6MWT) [ Time Frame: Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13 ]
  • Short physical performance battery (SPPB) [ Time Frame: Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13 ]

Central Contacts and Locations

Central contacts

Irina Timofte, MD, MS

2163347534Irina.Timofte@utsouthwestern.edu

Locations

UT Southwestern Medical Center

Recruiting

Dallas, Texas, United States, 75390

Contacts

Rhoda Annoh Gordon, PharmD, MPH

2146457108Rhoda.annohgordon@utsouthwestern.edu

More Information

Sponsor

University of Texas Southwestern Medical Center

Last update posted

Jun 25, 2026

Last verified

Jun, 2026

Keywords

  • Aging
  • Geriatic
  • Disability

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of Texas Southwestern Medical Center on 2026-06-25.