MTOR Inhibitors in Older Adults

NCT06727305 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: STU-2024-07981U01AG081450-01A1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Keywords

Aging; Geriatic; Disability

Outcome Measures

Primary Outcomes (15)

• Cmax for Sirolimus

  Maximum Sirolimus Concentration at Steady State (Cmax)

  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

  Maximum Everolimus Concentration at Steady State (Cmax)

  Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 12-hour post dose

• Ctrough for Sirolimus

  Trough Sirolimus Concentration at Steady State (Ctrough)

  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

  Trough Everolimus Concentration at Steady State (Ctrough)

  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

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

  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

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

  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

  Sirolimus Apparent Oral Clearance (CL/F)

  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

  Everolimus Apparent Oral Clearance (CL/F)

  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

  Pharmacodynamic parameter, S6K Activity, in Sirolimus cohorts

  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

  Pharmacodynamic parameter, S6K Activity, in Everolimus cohorts

  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

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

  Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13

• Erythrocyte sedimentation rate (ESR)

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

  Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13

• C-reactive protein (CRP)

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

  Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13

• 6-minute walk test (6MWT)

  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.

  Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13

• Short physical performance battery (SPPB)

  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.

  Day 1 Week 1 (Baseline), Week 5, Week 9, Week 13

Secondary Outcomes (6)

• Change in SASP response at 3 months follow-up

  Baseline, 3 months

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

  Baseline, 3 months

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

  Baseline, 3 months

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

  Baseline, 3 months

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

  Baseline, 3 months

Study Arms (6)

sirolimus 0.5 mg Arm

ACTIVE COMPARATOR

Participant would receive 0.5 mg of sirolimus.

Drug: Sirolimus 0.5 Mg Oral Tablet

sirolimus 1 mg Arm

ACTIVE COMPARATOR

Participant would receive 1 mg of sirolimus.

Drug: Sirolimus 1Mg Oral Tablet

sirolimus 2 mg Arm

ACTIVE COMPARATOR

Participant would receive 2 mg of sirolimus.

Drug: Sirolimus 2 MG Oral Tablet

everolimus 0.5 mg Arm

ACTIVE COMPARATOR

Participant would receive 0.5 mg of Everolimus.

Drug: Everolimus 0.5 MG Oral Tablet

everolimus 1 mg Arm

ACTIVE COMPARATOR

Participant would receive 1 mg of Everolimus.

Drug: Everolimus 1 MG Oral Tablet

everolimus 2 mg Arm

ACTIVE COMPARATOR

Participant would receive 2 mg of Everolimus.

Drug: Everolimus 2 MG Oral Tablet

Interventions

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 0.5 mg Arm

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 1 mg Arm

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.

sirolimus 2 mg Arm

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 0.5 mg Arm

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 1 mg Arm

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.

everolimus 2 mg Arm

Eligibility Criteria

• Age: 65 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Maryland, Baltimore: collaborator
• National Institute on Aging (NIA): collaborator
• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Interventions

Sirolimus; Tablets; Everolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Irina Timofte, MD, MS

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Irina Timofte, MD, MS

CONTACT

2163347534; Irina.Timofte@utsouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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

Study Record Dates

• First Submitted: November 20, 2024
• First Posted: December 10, 2024
• Study Start: February 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): November 13, 2027
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)