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NCT Number: NCT06727305

MTOR Inhibitors in Older Adults

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

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Key information

Conditions

Aging

Age range

65 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location status: Recruiting

Location contact

Rhoda Annoh Gordon, PharmD, MPH

CONTACT

[email protected]

2146457108

About this study

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

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Sirolimus 0.5 Mg Oral Tablet

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 1Mg Oral Tablet

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 Oral Tablet

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 Oral Tablet

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 Oral Tablet

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 Oral Tablet

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.

Primary outcomes

  1. 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

    Maximum Sirolimus Concentration at Steady State (Cmax)

  2. 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

    Maximum Everolimus Concentration at Steady State (Cmax)

  3. 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

    Trough Sirolimus Concentration at Steady State (Ctrough)

  4. 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

    Trough Everolimus Concentration at Steady State (Ctrough)

  5. 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

    Sirolimus Area Under the Curve from Time Zero to End of Dosing Interval (AUCtau) at Steady State

  6. 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

    Everolimus Area Under the Curve from Time Zero to End of Dosing Interval (AUCtau) at Steady State

  7. 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

    Sirolimus Apparent Oral Clearance (CL/F)

  8. 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

    Everolimus Apparent Oral Clearance (CL/F)

  9. 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

    Pharmacodynamic parameter, S6K Activity, in Sirolimus cohorts

  10. 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

    Pharmacodynamic parameter, S6K Activity, in Everolimus cohorts

  11. Senescence-associated secretory phenotype (SASP) index

    Time frame: Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13

    Clinical biomarker parameter (SASP) index is a clinical biomarker parameter that measures the level of proteins secreted by senescent cells in the body.

  12. Erythrocyte sedimentation rate (ESR)

    Time frame: Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13

    Clinical biomarker parameter (ESR) is a blood test that detects and monitors inflammation in the body.

  13. C-reactive protein (CRP)

    Time frame: Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13

    A measure of Clinical biomarker parameter (CRP), is an inflammatory marker.

  14. 6-minute walk test (6MWT)

    Time frame: Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13

    The 6MWT is simply a record of the distance (in meters) traveled by a given patient at his or her self-selected walking speed over a period of six minutes.

  15. Short physical performance battery (SPPB)

    Time frame: Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13

    Clinical biomarker parameter (SPPB) assesses lower extremity function in older adults. The test battery consists of three physical tasks (walking, sit-to-stand and balance) to assess functional mobility. The test will be performed according to standardized procedure. The maximal total score is 12 and higher total scores indicate a better lower extremity functioning.

Secondary outcomes

  1. Change in SASP response at 3 months follow-up

    Time frame: Baseline, 3 months

    SASP (senescence-associated secretory phenotype) index score is quantified using blood work comparing results at baseline and at 3 months follow-up. Patients with high SASP scores have a poor survival rate, while patients with low SASP scores have a good survival rate.

  2. Change in Laboratory Biomarker response (ESR) from baseline at 3 months follow-up

    Time frame: Baseline, 3 months

    Feasibility of collecting the laboratory biomarker - Erythrocyte sedimentation rate (ESR) is assessed by change in blood work readings ((millimeters per hour [mm/hour])) at 3 months follow-up.

  3. Change in laboratory Biomarker response (CRP) from baseline at 3 months follow-up

    Time frame: Baseline, 3 months

    Feasibility of collecting the laboratory biomarker- C-Reactive Protein (CRP) is assessed by change in blood work readings (mg/dl) at 3 months follow-up.

  4. Change in laboratory Biomarker response (S6K activity) from baseline at 3 months follow-up

    Time frame: Baseline, 3 months

    Feasibility of collecting the laboratory biomarker- S6 Kinase (S6K) activity is assessed by change in blood work readings (mg/dl) at 3 months follow-up.

  5. Change in laboratory Biomarker response (mitochondrial function) from baseline at 3 months follow-up

    Time frame: Baseline, 3 months

    Feasibility of collecting the laboratory biomarker (mitochondrial function) is assessed by change in blood work readings at 3 months follow-up. The mitochondrial function will be measured through the Bioenergetic Health Index. The Bioenergetic Health Index (BHI) is calculated using the following formula: BHI=(ATP-linked×reserve capacity)/(proton leak×non-mitochondrial) - as described by Chacko et al. The expected range is 0-100.

  6. Change in laboratory Biomarker response (metabolomics) from baseline at 3 months follow-up

    Time frame: Baseline, 3 months

    Feasibility of collecting the laboratory biomarker (metabolomics) is assessed by change in blood work readings at 3 months follow-up. Changes in blood metabolomics are quantified by measuring the concentration levels of individual metabolites within a blood sample using techniques like mass spectrometry (MS) or nuclear magnetic resonance (NMR) spectroscopy, where the relative abundance of each metabolite is compared between different samples, allowing for identification of changes in metabolic pathways based on variations in metabolite levels. The unit of measure is "concentration", usually expressed in micromolar (µM) or millimolar (mM), as it represents the quantity of a specific metabolite per unit volume of the sample.

Study contacts

Contact information is provided by the study sponsor or research team.

Irina Timofte, MD, MS

CONTACT

[email protected]

2163347534

Sponsors and collaborators

Lead sponsor

University of Texas Southwestern Medical Center

Other

Collaborators

  • National Institute on Aging (NIA)
  • University of Maryland, Baltimore

Registry information

Official study title

Characterization of mTOR Inhibitor Pharmacokinetics and Pharmacodynamics in Older Adults .

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Dec 10, 2024
Registry last updated
Jun 25, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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