MTOR Inhibitors in Older Adults

NCT ID: NCT06727305

Last Updated: 2026-02-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-28

Study Completion Date

2027-11-13

Brief Summary

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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

Detailed Description

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Study Objectives To characterize Pharmacokinetics (PK) and Pharmacodynamics (PD) of mTOR Inhibitors and determine whether mTOR Inhibitors will improve phenotypic biomarkers of aging as measured by SASP (senescence-associated secretory phenotype) index score at 3 months follow-up in older adults.

Specific Aims:

Aim 1: To characterize Pharmacokinetics (PK) and Pharmacodynamics (PD) of mTOR Inhibitors (sirolimus and everolimus) in older adults.

Aim 2: To determine whether mTOR Inhibitors will improve phenotypic biomarkers of aging as measured by SASP (senescence-associated secretory phenotype) index score at 3 months follow-up.

Exploratory Aim 3: We will also assess the feasibility of collecting the laboratory biomarkers (ESR, CRP, S6K activity, mitochondrial function, metabolomics) and data regarding the functional biomarkers of aging measured by walking speed, chair stand, standing balance, grip strength

Conditions

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Aging

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Patients who will be randomized in 1:1:1:1:1:1 ratios to receive oral tablet doses of sirolimus and everolimus with concentrations of 0.5mg, 1mg, 2mg each
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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sirolimus 0.5 mg Arm

Participant would receive 0.5 mg of sirolimus.

Group Type ACTIVE_COMPARATOR

Sirolimus 0.5 Mg Oral Tablet

Intervention Type DRUG

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 1 mg Arm

Participant would receive 1 mg of sirolimus.

Group Type ACTIVE_COMPARATOR

Sirolimus 1Mg Oral Tablet

Intervention Type DRUG

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 Arm

Participant would receive 2 mg of sirolimus.

Group Type ACTIVE_COMPARATOR

Sirolimus 2 MG Oral Tablet

Intervention Type DRUG

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 Arm

Participant would receive 0.5 mg of Everolimus.

Group Type ACTIVE_COMPARATOR

Everolimus 0.5 MG Oral Tablet

Intervention Type DRUG

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 Arm

Participant would receive 1 mg of Everolimus.

Group Type ACTIVE_COMPARATOR

Everolimus 1 MG Oral Tablet

Intervention Type DRUG

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 Arm

Participant would receive 2 mg of Everolimus.

Group Type ACTIVE_COMPARATOR

Everolimus 2 MG Oral Tablet

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

65 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Maryland, Baltimore

OTHER

Sponsor Role collaborator

National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Irina Timofte

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Irina Timofte, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Texas Southwestern Medical Center

Locations

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UT Southwestern Medical Center

Dallas, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Irina Timofte, MD, MS

Role: CONTACT

2163347534

Facility Contacts

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Rhoda Annoh Gordon, PharmD, MPH

Role: primary

2146457108

Other Identifiers

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1U01AG081450-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU-2024-0798

Identifier Type: -

Identifier Source: org_study_id

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