MTOR Inhibitors in Older Adults

ConditionAging
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age65-80
SponsorUniversity of Texas Southwestern Medical Center

About this trial

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

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Community-dwelling adults

Patients should be 65 Years and older

Patients is able to understand and follow trial procedures

Disqualifiers

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;

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

Treatment groups

60 Participants
are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Group A: sirolimus 0.5 mg ArmActive comparator 1 intervention
Group B: sirolimus 1 mg ArmActive comparator 1 intervention
Group C: sirolimus 2 mg ArmActive comparator 1 intervention
Group D: everolimus 0.5 mg ArmActive comparator 1 intervention
Group E: everolimus 1 mg ArmActive comparator 1 intervention
Group F: everolimus 2 mg ArmActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Cmax for Sirolimus

Maximum Sirolimus Concentration at Steady State (Cmax)

Time frame
Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24-hour post dose
2

Cmax for Everolimus

Maximum Everolimus Concentration at Steady State (Cmax)

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

Ctrough for Sirolimus

Trough Sirolimus Concentration at Steady State (Ctrough)

Time frame
Predose (0 hour) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24-hour post dose
4

Ctrough for Everolimus

Trough Everolimus Concentration at Steady State (Ctrough)

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

Secondary outcomes

1

Change in SASP response at 3 months follow-up

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.

Time frame
Baseline, 3 months
2

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

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.

Time frame
Baseline, 3 months
3

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

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.

Time frame
Baseline, 3 months
4

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

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.

Time frame
Baseline, 3 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Texas Southwestern Medical Center

Lead sponsor

University of Maryland, Baltimore

Collaborator

National Institute on Aging (NIA)

Collaborator