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Recruiting NCT06727305

MTOR Inhibitors in Older Adults

Phase I / Phase II Interventional Aging

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Sirolimus 0.5 Mg Oral Tablet, Sirolimus 1Mg Oral Tablet, Sirolimus 2 MG Oral Tablet, Everolimus 0.5 MG Oral Tablet.
Who it may be relevant to
Registry conditions: Aging. Basic parameters: 65 years — 80 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

Characterization of mTOR Inhibitor Pharmacokinetics and Pharmacodynamics in Older Adults .

Overview

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

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

Interventions

  • Drug 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Primary outcome measures

  • 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]
Secondary outcome measures (6)
  • Change in SASP response at 3 months follow-up [Time frame: Baseline, 3 months]
  • Change in Laboratory Biomarker response (ESR) from baseline at 3 months follow-up [Time frame: Baseline, 3 months]
  • Change in laboratory Biomarker response (CRP) from baseline at 3 months follow-up [Time frame: Baseline, 3 months]
  • Change in laboratory Biomarker response (S6K activity) from baseline at 3 months follow-up [Time frame: Baseline, 3 months]
  • Change in laboratory Biomarker response (mitochondrial function) from baseline at 3 months follow-up [Time frame: Baseline, 3 months]
  • Change in laboratory Biomarker response (metabolomics) from baseline at 3 months follow-up [Time frame: Baseline, 3 months]

Eligibility criteria

Inclusion criteria

  • Community-dwelling adults
  • Patients should be 65 Years and older
  • Patients is able to understand and follow trial procedures

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Prevention

Study locations

United States · 1 center
  • UT Southwestern Medical Center — Dallas

Identifiers

NCT: NCT06727305 · STU-2024-0798 · 1U01AG081450-01A1

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗