Everolimus Aging Study

NCT05835999 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: 2021-15191U01AG076941-01A534255Protocol Version 4/30/2025
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this project is to determine if mTORC1 inhibition by 24 weeks of daily (0.5 mg/day) or weekly (5 mg/week) everolimus can safely improve physiological and molecular hallmarks of aging in humans. Participants who are 55-80 years old and insulin resistant or prediabetic will be randomized to treatment and can expect to be on study for up to approximately 38 weeks. Participants aged 18-35 will not receive the intervention and can expect to be on study for up to approximately 8 weeks.

Conditions

Aging; Insulin Resistance

Keywords

rapamycin; rapamycin analog; mTOR; everolimus

Outcome Measures

Primary Outcomes (1)

• Metabolic Function: Change in peripheral insulin sensitivity

  Change (pre to post) in peripheral insulin sensitivity measured by glucose disposal rate relative to circulating insulin during a dual tracer 75g oral glucose tolerance test (OGTT).

  0 (pre-intervention) and 24 weeks (post-intervention)

Secondary Outcomes (9)

• Cardiac Function: Change in fractional shortening velocity

  0 (pre-intervention) and 24 weeks (post-intervention)

• Cognitive Function: Change in cerebral blood flow

  0 (pre-intervention) and 24 weeks (post-intervention)

• Safety: Number of Participants with Adverse Events

  up to 36 weeks

• Safety: Change in concentration of blood metabolites/enzymes

  0 (pre-intervention), 4, 8, 12, 16, 20, and 24 weeks (post-intervention)

• Safety: Changes in concentration of blood lipids

  0 (pre-intervention), 4, 8, 12, 16, 20, and 24 weeks (post-intervention)

Other Outcomes (16)

• Physical Function: Change in cardiorespiratory fitness

  0 (pre-intervention) and 24 weeks (post-intervention)

• Physical Function: Change in maximal knee extensor muscle power

  0 (pre-intervention) and 24 weeks (post-intervention)

• Physical Function: Change in maximal knee extensor muscle strength

  0 (pre-intervention) and 24 weeks (post-intervention)

Study Arms (4)

Daily Everolimus (0.5 mg/day) and Weekly Placebo

EXPERIMENTAL

Once daily (0.5 mg) everolimus and once weekly placebo taken orally for 24 weeks

Drug: Everolimus 0.5 MG once per day; Drug: Placebo once per week

Daily Placebo and Weekly Everolimus (5mg/week)

EXPERIMENTAL

Once daily placebo and once weekly (5 mg) everolimus taken orally for 24 weeks

Drug: Everolimus 5 MG once per week; Drug: Placebo once per day

Daily Placebo and Weekly Placebo

PLACEBO COMPARATOR

Once daily placebo and once weekly placebo taken orally for 24 weeks

Drug: Placebo once per day; Drug: Placebo once per week

Young Adult Reference Group

NO INTERVENTION

Baseline testing only

Interventions

Placebo once per day DRUG

No therapeutic effect

Daily Placebo and Weekly Everolimus (5mg/week); Daily Placebo and Weekly Placebo

Placebo once per week DRUG

No therapeutic effect

Daily Everolimus (0.5 mg/day) and Weekly Placebo; Daily Placebo and Weekly Placebo

Everolimus 0.5 MG once per day DRUG

Everolimus is considered an mTOR kinase inhibitor

Daily Everolimus (0.5 mg/day) and Weekly Placebo

Everolimus 5 MG once per week DRUG

Everolimus is considered an mTOR kinase inhibitor

Daily Placebo and Weekly Everolimus (5mg/week)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Free of overt chronic disease
• Willing to provide informed consent
• Willing to comply with all study procedures and be available for the duration of the study
• Able to use and be contacted by the telephone
• Ability to take oral medication
• Insulin Resistant defined by HOMA-IR greater than or equal to 1.5 or prediabetic defined as:
• impaired fasting glucose (100-125 mg/dL)
• HbA1c (5.7-6.4 percent)
• glucose 2 hours after a 75 gram oral glucose tolerance test (140-199 mg/dL)
• previous diagnosis of prediabetes in the past year
• Not planning to change diet or physical activity status
• Adequate organ function as indicated by standard laboratory tests: hematology (complete blood count), clinical chemistry and urinalysis
• Females of childbearing potential must have a negative urine pregnancy test before DEXA and before the oral glucose tolerance test (OGTT). A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

You may not qualify if:

• Pregnancy or breastfeeding
• Heart disease
• Cerebrovascular disease
• Cancer or less than 5 years in remission
• Chronic respiratory disease
• Chronic liver disease
• Diabetes
• Alzheimer's
• Chronic kidney disease
• For those undergoing muscle biopsy: problems with bleeding, on medication that prolongs bleeding time
• Taking azathioprine (Imuran), cyclosporine (Gengraf, Neoral, Sandimmune), dexamethasone (Decadron, Dexpak), methotrexate (Rheumatrex, Trexall), prednisolone (Orapred, Pediapred, Prelone), prednisone (Sterapred), sirolimus (Rapamune), and tacrolimus (Prograf) or other medications proposed to lower the immune system. Daily use of high potency topical corticosteroids used on greater than or equal to 10% of body surface area will not be eligible. Nasal sprays or inhaled corticosteroids will be reviewed on a case-by-case basis.
• Taking strong or moderate CYP3A4 and/or P-glycoprotein (PgP) inhibitors
• Taking strong CYP3A4 activators
• Taking daily NSAIDs with the exception of baby asprin (81 mg)
• Subjects who are not willing to restrict the use of grapefruit, grapefruit juice, and other foods that are known to inhibit cytochrome P450 and PgP activity and may increase everolimus exposures and should be avoided during treatment

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Wisconsin-Madison

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Adam Konopka, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized, placebo-controlled, double-blind, 24-week clinical trial using everolimus in middle-aged to older adults. This study will follow a "double-dummy" design where participants will be randomized 1:1:1 in a double-blinded fashion to one of three groups: 1) everolimus once daily (0.5 mg/day) plus placebo once weekly, 2) placebo once daily plus everolimus once weekly (5mg/week) or 3) placebo once daily and placebo once weekly. The double dummy design preserves the double-blind for both placebo versus everolimus and for daily versus weekly dosing schedules. Everolimus and placebo will be over encapsulated to be indistinguishable from one another. There will also be a group of young, healthy individuals who will complete baseline testing only and not the intervention. This group allows the determination if everolimus changes any molecular and physiological outcomes in older adults toward that of a young, healthy reference group.

Study Record Dates

• First Submitted: April 3, 2023
• First Posted: May 1, 2023
• Study Start: March 24, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data from this study may be requested from other researchers years after the completion of the study endpoints by contacting Dr. Adam Konopka or the NIA BioBank Repository.

Locations

US (1)