AgingPhase 2EVERLASTNCT05835999
Everolimus Aging Study
A Phase 2 study testing Everolimus 0.5 MG once per day and Everolimus 5 MG once per week in people with Aging and Insulin Resistance, run by University of Wisconsin, Madison at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging, Insulin Resistance
- What is being tested?
- Everolimus 0.5 MG once per day and Everolimus 5 MG once per week
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 106 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Mar 2023to 22 Jul 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
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- 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)
- Women of childbearing potential in sexual relationships with men must use an acceptable method of contraception from 30 days prior to enrollment until 4 weeks after completing study visits. Males must agree to avoid impregnation of women during and for four weeks after completing study visits through use of an acceptable method of contraception.
- Note: Includes, but is not limited to, barrier with additional spermicidal foam or jelly, intrauterine device, hormonal contraception (started at least 30 days prior to study enrollment), intercourse with men who underwent vasectomy.
- Inclusion Criteria: Younger Adults aged 18-35 (No intervention)
- Free overt chronic disease
Who cannot join
- Pregnancy or breastfeeding
- Heart disease
- Cerebrovascular disease
- Cancer or less than 5 years in remission
- Chronic respiratory disease
- Chronic liver disease
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- 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
- Subjects who are not willing to restrict the use of St. John's Wort (Hypericum perforatum) because it may decrease everolimus exposure unpredictably
- Subjects who are not willing to avoid blood donations 8 weeks prior to the first visit and 8 weeks after the last visit
- For those undergoing MRI, contraindications with MRI which could include metal on your body
- Low white-blood cell count (<3,000 cell/µL)
- History of stomatitis or ulcers in the mouth
- Those on glucose lowering drugs
- Participating in intensive exercise training program (high to moderate intensity exercise greater than 150 minutes per week) or planning to start new exercise program during study period
- Tobacco use
- Allergies to lidocaine or everolimus
- Subjects currently enrolled in other clinical trials. Subjects may be eligible after a washout period that will be reviewed on a case by case basis.
- Individuals with limited English proficiency
- Subjects who are planning to have elective surgery 12 weeks prior to or during the intervention
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Wisconsin-Madison
Madison, Wisconsin, 53705
About this study
Official title: Clinical Evaluation of mTORC1 Inhibition for Geroprotection
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.
Read the detailed description
Pharmacological inhibition of mechanistic target of rapamycin (mTOR) has been repeatedly demonstrated to extend lifespan and prevent or delay several age-related diseases in diverse model systems. However, the risk of potentially serious side effects in humans have thus far prevented the long-term use of the mTOR inhibitor rapamycin as a therapy for aging and age-related diseases. Therefore, it remains unknown whether rapamycin or rapamycin analogs (rapalogs) can safely improve healthy aging in humans.
The objective of this project is to determine if 24 weeks of daily low dose (0.5 mg/day) or weekly intermittent (5 mg/week) treatment with the rapalog everolimus can safely improve physiological and molecular hallmarks of aging in middle-aged to older insulin resistant adults who are at high risk for nearly every age-related condition.
Using a double-blinded, randomized, placebo-controlled clinical trial, the investigators will perform a battery of gold-standard and innovative techniques to test the hypothesis that daily low dose or weekly everolimus treatment will improve 4 inter-related domains of physiological aging: metabolic, cardiac, cognitive, and physical function. The investigators will also assess the incidence of adverse events and changes from baseline blood chemistry, blood cell counts, lipids, glucose, and insulin.
To comprehensively examine the molecular target specificity and the impact on mechanisms of aging by everolimus, the team will evaluate mTORC1 and mTORC2 signaling, assess mitochondrial bioenergetics, and perform a multi-omics approach (epigenomics, transcriptomics, proteomics, lipidomics, and metabolomics) in blood and/or muscle biopsy samples.
- Conditions
- Aging, Insulin Resistance
- Being tested
- Everolimus 0.5 MG once per day, Everolimus 5 MG once per week, Placebo once per day, Placebo once per week
- Keywords
- rapamycin, rapamycin analog, mTOR, everolimus
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Everolimus 0.5 MG once per dayDrug
Everolimus is considered an mTOR kinase inhibitor
Everolimus 5 MG once per weekDrug
Everolimus is considered an mTOR kinase inhibitor
Placebo once per dayDrug
No therapeutic effect
Placebo once per weekDrug
No therapeutic effect
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: Placebo once per day; Drug: Placebo once per week |
| Young Adult Reference Group | No intervention | Baseline testing only |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 0 (pre-intervention) and 24 weeks (post-intervention)
Secondary outcomes (9)
Cardiac Function: Change in fractional shortening velocity
Cardiac Function will be assessed by measuring the change in fractional shortening velocity determined during the echocardiogram.
Measured: 0 (pre-intervention) and 24 weeks (post-intervention)
Cognitive Function: Change in cerebral blood flow
Change in blood flow in posterior cingulate, medial temporal lobe (hippocampus and parahippocampus) and inferior frontal cortex assessed by brain MRI (4D Flow, Arterial Spin Labeling).
Measured: 0 (pre-intervention) and 24 weeks (post-intervention)
Safety: Number of Participants with Adverse Events
Safety will be measured in part by reporting the number of participants with adverse events.
Measured: up to 36 weeks
Safety: Change in concentration of blood metabolites/enzymes
Safety will be measured in part by reporting the change in the blood concentration of metabolites and enzymes as assessed by a complete metabolic panel
Measured: 0 (pre-intervention), 4, 8, 12, 16, 20, and 24 weeks (post-intervention)
Safety: Changes in concentration of blood lipids
Safety will be measured in part by reporting the changes in the concentration of blood lipids.
Measured: 0 (pre-intervention), 4, 8, 12, 16, 20, and 24 weeks (post-intervention)
Safety: Changes in number of blood cells
Safety will be measured in part by reporting the changes in the number of blood cells as determined by blood cell count with differential
Measured: 0 (pre-intervention), 4, 8, 12, 16, 20, and 24 weeks (post-intervention)
Safety: Changes in HbA1c (%)
Safety will be measured in part by reporting the changes in the percentage of glycosylated hemoglobin (Hba1c (%))
Measured: pre-intervention baseline, post-intervention up to 24 weeks
Safety: Changes in concentration of insulin
Safety will be measured in part by reporting the changes in fasting blood insulin concentration
Measured: 0 (pre-intervention), 4, 8, 12, 16, 20, and 24 weeks (post-intervention)
mTOR signaling: Change in phosphorylation of downstream targets of mTOR complex 1 and complex 2 as assessed by immunoblotting and immunoprecipitation.
mTOR signaling will be assessed by measuring the change in phosphorylation of downstream targets of mTOR complex 1 and complex 2 via immunoblotting in muscle and/or peripheral mononuclear blood cells (PMBCs).
Measured: pre-intervention baseline, post-intervention up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2023
- Study start24 Mar 2023
- Primary completion30 Jun 2026
- Study completion22 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AgingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Adam Konopka, PhD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05835999
- Sponsor's protocol ID
- 2021-1519
- Other IDs
- 1U01AG076941-01, A534255, Protocol Version 6/5/2026
- Acronym
- EVERLAST
- Status last verified
- Sep 2026
- First submitted
- 3 Apr 2023
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Evaluation of mTORC1 Inhibition for Geroprotection
- ClinicalTrials.gov ID
- NCT05835999
- Acronym / sponsor ID
- EVERLAST / 2021-1519
- Conditions
- Aging, Insulin Resistance
- Keywords
- rapamycin, rapamycin analog, mTOR, everolimus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 24 Mar 2023 (actual)
- Primary completion
- 30 Jun 2026 (actual)
- Study completion
- 22 Jul 2026 (actual)
- First posted
- 1 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Pharmacological inhibition of mechanistic target of rapamycin (mTOR) has been repeatedly demonstrated to extend lifespan and prevent or delay several age-related diseases in diverse model systems. However, the risk of potentially serious side effects in humans have thus far prevented the long-term use of the mTOR inhibitor rapamycin as a therapy for aging and age-related diseases. Therefore, it remains unknown whether rapamycin or rapamycin analogs (rapalogs) can safely improve healthy aging in humans.
The objective of this project is to determine if 24 weeks of daily low dose (0.5 mg/day) or weekly intermittent (5 mg/week) treatment with the rapalog everolimus can safely improve physiological and molecular hallmarks of aging in middle-aged to older insulin resistant adults who are at high risk for nearly every age-related condition.
Using a double-blinded, randomized, placebo-controlled clinical trial, the investigators will perform a battery of gold-standard and innovative techniques to test the hypothesis that daily low dose or weekly everolimus treatment will improve 4 inter-related domains of physiological aging: metabolic, cardiac, cognitive, and physical function. The investigators will also assess the incidence of adverse events and changes from baseline blood chemistry, blood cell counts, lipids, glucose, and insulin.
To comprehensively examine the molecular target specificity and the impact on mechanisms of aging by everolimus, the team will evaluate mTORC1 and mTORC2 signaling, assess mitochondrial bioenergetics, and perform a multi-omics approach (epigenomics, transcriptomics, proteomics, lipidomics, and metabolomics) in blood and/or muscle biopsy samples.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Daily Everolimus (0.5 mg/day) and Weekly Placebo | Experimental | Drug: Everolimus 0.5 MG once per day, Drug: Placebo once per weekOnce daily (0.5 mg) everolimus and once weekly placebo taken orally for 24 weeks |
| Daily Placebo and Weekly Everolimus (5mg/week) | Experimental | Drug: Everolimus 5 MG once per week, Drug: Placebo once per dayOnce daily placebo and once weekly (5 mg) everolimus taken orally for 24 weeks |
| Daily Placebo and Weekly Placebo | Placebo comparator | Drug: Placebo once per day, Drug: Placebo once per weekOnce daily placebo and once weekly placebo taken orally for 24 weeks |
| Young Adult Reference Group | No intervention | –Baseline testing only |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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
Key exclusion criteria (27 listed)
- Pregnancy or breastfeeding
- Heart disease
- Cerebrovascular disease
- Cancer or less than 5 years in remission
- Chronic respiratory disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Everolimus 0.5 MG once per dayEverolimus is considered an mTOR kinase inhibitor | Drug | Daily Everolimus (0.5 mg/day) and Weekly Placebo |
| Everolimus 5 MG once per weekEverolimus is considered an mTOR kinase inhibitor | Drug | Daily Placebo and Weekly Everolimus (5mg/week) |
| Placebo once per dayNo therapeutic effect | Drug | Daily Placebo and Weekly Everolimus (5mg/week), Daily Placebo and Weekly Placebo |
| Placebo once per weekNo therapeutic effect | Drug | Daily Everolimus (0.5 mg/day) and Weekly Placebo, Daily Placebo and Weekly Placebo |
Primary outcome
Metabolic Function: Change in peripheral insulin sensitivity
Time frame: 0 (pre-intervention) and 24 weeks (post-intervention)
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).
9 secondary outcomes
Cardiac Function: Change in fractional shortening velocity
Time frame: 0 (pre-intervention) and 24 weeks (post-intervention)
Cognitive Function: Change in cerebral blood flow
Time frame: 0 (pre-intervention) and 24 weeks (post-intervention)
Safety: Number of Participants with Adverse Events
Time frame: up to 36 weeks
Safety: Change in concentration of blood metabolites/enzymes
Time frame: 0 (pre-intervention), 4, 8, 12, 16, 20, and 24 weeks (post-intervention)
Safety: Changes in concentration of blood lipids
Time frame: 0 (pre-intervention), 4, 8, 12, 16, 20, and 24 weeks (post-intervention)
Safety: Changes in number of blood cells
Time frame: 0 (pre-intervention), 4, 8, 12, 16, 20, and 24 weeks (post-intervention)
Safety: Changes in HbA1c (%)
Time frame: pre-intervention baseline, post-intervention up to 24 weeks
Safety: Changes in concentration of insulin
Time frame: 0 (pre-intervention), 4, 8, 12, 16, 20, and 24 weeks (post-intervention)
mTOR signaling: Change in phosphorylation of downstream targets of mTOR complex 1 and complex 2 as assessed by immunoblotting and immunoprecipitation.
Time frame: pre-intervention baseline, post-intervention up to 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adam Konopka, PhD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus 0.5 MG once per day and Everolimus 5 MG once per week in people with Aging and Insulin Resistance, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metabolic Function: Change in peripheral insulin sensitivity (time frame: 0 (pre-intervention) and 24 weeks (post-intervention)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026; AzTrials last refreshed its copy on 31 Oct 2026.