MTOR Inhibitors in Older Adults

The University of Texas System (UT)

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Aging

Treatments: Drug: Sirolimus 2 MG Oral Tablet; Drug: Everolimus 0.5 MG Oral Tablet; Drug: Sirolimus 1Mg Oral Tablet; Drug: Everolimus 2 MG Oral Tablet; Drug: Everolimus 1 MG Oral Tablet; Drug: Sirolimus 0.5 Mg Oral Tablet

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06727305

STU-2024-0798

1U01AG081450-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Full description

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

Enrollment: 60 estimated patients

Sex: All

Ages: 65 to 80 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 6 patient groups

sirolimus 0.5 mg Arm

Active Comparator group

Description:

Participant would receive 0.5 mg of sirolimus.

Treatment:

Drug: Sirolimus 0.5 Mg Oral Tablet

sirolimus 1 mg Arm

Active Comparator group

Description:

Participant would receive 1 mg of sirolimus.

Treatment:

Drug: Sirolimus 1Mg Oral Tablet

sirolimus 2 mg Arm

Active Comparator group

Description:

Participant would receive 2 mg of sirolimus.

Treatment:

Drug: Sirolimus 2 MG Oral Tablet

everolimus 0.5 mg Arm

Active Comparator group

Description:

Participant would receive 0.5 mg of Everolimus.

Treatment:

Drug: Everolimus 0.5 MG Oral Tablet

everolimus 1 mg Arm

Active Comparator group

Description:

Participant would receive 1 mg of Everolimus.

Treatment:

Drug: Everolimus 1 MG Oral Tablet

everolimus 2 mg Arm

Active Comparator group

Description:

Participant would receive 2 mg of Everolimus.

Treatment:

Drug: Everolimus 2 MG Oral Tablet