AgingPhase 1NCT05949658
Rapalog Pharmacology (RAP PAC) Study
A Phase 1 study testing Sirolimus and Everolimus in people with Aging, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
The objective of RAP PAC is to identify safe and effective weekly dose(s) for the mTOR inhibitors sirolimus and everolimus that intervene on the underlying fundamental biology of aging. Read more about this study
- Who is it for?
- Ages 55 to 89 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging
- What is being tested?
- Sirolimus and Everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 15 May 2024to Dec 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 55 to 89 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Middle-age adults 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 telephone
- Ability to take oral medication
- Not planning to change diet or physical activity status
- Adequate organ function as indicated by standard laboratory tests: hematology (complete blood count), and clinical chemistry
- 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
Who cannot join
- Heart disease (history, abnormal ECG)
- Cerebrovascular disease (history)
- Cancer or less than 5 years in remission (history)
- Chronic respiratory disease (history, FEV1/FVC < 70, FEV1 < 80% predicted)
- Chronic liver disease (history, abnormal blood liver panel, ALT >104 IU/L, AST >80 IU/L)
- Diabetes (history, HbA1C ≥ 6.5, fasting blood glucose≥126 mg/dl, OGTT ≥ 200 mg/dl at 2 hrs.)
Show all 26Show fewer
- Alzheimer's (history)
- Chronic kidney disease (history, abnormal blood kidney panel including serum creatinine>1.4, eGFR≤60 ml/min/1.73m2)
- Problems with bleeding, on medication that prolongs bleeding time (if subject cannot safely stop prior to biopsy)
- 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
- Taking strong or moderate CYP3A4 and/or P-glycoprotein (PgP) inhibitors such as ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem
- Taking strong or moderate CYP3A4 and/or P-glycoprotein (PgP) inhibitors such as ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem
- Taking strong CYP3A4 activators such as phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital
- Taking daily NSAIDs such as ibuprofen, naproxen, aspirin and others, with the exception of baby aspirin (81mg)
- Subjects who are not willing to restrict the use of grapefruit, grapefruit juice, cannabidiol (CBD) and other foods/substances 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
- Low white-blood cell count (<4,000 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 or nicotine use
- Allergies to lidocaine, sirolimus, 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. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Wisconsin
Madison, Wisconsin, 53705
Adam Konopka, PhD
About this study
Official title: Safer mTOR Inhibition for Human Geroprotection
The objective of RAP PAC is to identify safe and effective weekly dose(s) for the mTOR inhibitors sirolimus and everolimus that intervene on the underlying fundamental biology of aging. Participants who are 55-89 years old that are free of overt chronic diseases will be assigned to either 6 weeks of sirolimus or everolimus (5 mg, 10 mg, or 15 mg once per week). The investigators will complete the everolimus arm first and then subsequently complete the sirolimus arm of the study. Total time on study would be up to 17 weeks to complete baseline and follow up visits.
Read the detailed description
The mTOR inhibitor rapamycin and rapamycin analogs (rapalogs) extend healthspan and/or lifespan in multiple model systems. However, the risk of adverse events and dose limiting toxicities in humans have thus far precluded the long-term prophylactic use of mTOR inhibitors as a therapy for aging and age-related diseases. The pharmacokinetics and pharmacodynamics (PK/PD) data for mTOR inhibitors in older adults is currently unknown and has prevented the identification of a safe dosage that could maximize health-span extension and minimize adverse effects.
RAP PAC will identify a recommended phase 2 trial dose for sirolimus and everolimus in older men and women by performing a phase 1, dose finding study that evaluates PK/PD, safety and tolerability, and mTOR signaling using conventional as well as novel approaches. Overall, the investigators will pair comprehensive molecular and pharmacologic approaches to evaluate PK/PD in humans and identify dosing regimens that safely inhibit mTOR complex 1 (mTORC1) to intervene in the biology of aging.
- Conditions
- Aging
- Being tested
- Sirolimus, Everolimus
- Keywords
- Rapamycin, Rapamycin analog, mTOR, mTOR inhibitor, sirolimus, everolimus, rapamune
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamycin
5mg, 10mg, or 15mg once weekly sirolimus
EverolimusDrug
5mg, 10mg, or 15mg once weekly everolimus
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus | Experimental | 1mg tablets of sirolimus that total the assigned dose Receives: Drug: Sirolimus |
| Everolimus | Experimental | 1mg tablets of everolimus that total the assigned dose Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limited Toxicities (DLTs)
A recommended phase 2 dose (RP2D) will be determined through evaluating dose limiting toxicities (DLT), which is defined as ≥Grade 2 adverse event following CTCAE v6.0.
Measured: Through study completion, an average 3 years
Secondary outcomes (13)
Time course of drug concentration in blood
Using PK parameters of Peak Plasma Concentration (Cmax, Cmin), determine duration of concentration of drug in blood measured pre dose, and 0.5, 1.5, 4, 48, and 168 hours post dose
Measured: First dose to 168 hours post dose
Time course of drug concentration in blood
Using PK parameters of Area under the plasma concentration versus time curve (AUC, T1/2), determine duration of concentration of drug in blood measured pre dose, and 0.5, 1.5, 4, 48, and 168 hours post dose
Measured: First dose to 168 hours post dose
Change in mTOR signaling in blood and muscle
To be evaluated through immunoblotting and immunoprecipitation
Measured: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in concentration of metabollites
Metabolomics: Change in concentration of blood and/or skeletal muscle metabolites as assessed by liquid chromatography mass spectrometry
Measured: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in concentration of lipid species
Lipidomics: Change in the concentration of lipid species in blood and/or skeletal muscle as assessed by liquid chromatography mass spectrometry
Measured: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in transcriptome
Change in skeletal muscle and whole blood transcripts assessed via RNA sequencing
Measured: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in glucose tolerance
Assess change in glucose tolerance by area under the curve
Measured: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in whole body insulin sensitivity
Insulin sensitivity as assessed by the Matsuda Index.
Measured: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in glucose variability
Glucose Variability will be assessed via continuous glucose monitoring during two occasions during weeks 0, and 6 by measuring the change in range.
Measured: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in glucose variability
Glucose Variability will be assessed via continuous glucose monitoring during two occasions during weeks 0, and 6 by measuring the change in total standard deviation.
Measured: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in glucose variability
Glucose Variability will be assessed via continuous glucose monitoring during two occasions during weeks 0, and 6 by measuring the change in mean daily differences (MODD).
Measured: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in glucose variability
Glucose Variability will be assessed via continuous glucose monitoring during two occasions during weeks 0, and 6 by measuring the change in the overall net glycemic action over a 4-h and 8-h period (CONGA4; CONGA8).
Measured: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in insulin resistance
Measured by change in homeostatic model of insulin resistance (HOMA-IR).
Measured: 0 (pre-intervention) and 6 weeks (post-intervention)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2023
- Study start15 May 2024
- Primary completionMar 2027 (estimated)
- Study completionDec 2028 (estimated)
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 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The Bayesian Optimal Interval Design (BOIN) will be used to perform a phase I, dose finding trial in healthy older men and women (55-89yrs) for the mTOR inhibitors sirolimus and everolimus. Middle-aged to older adults will be treated with either sirolimus or everolimus for 6 weeks. All participants will take one capsule weekly. This dose escalation trial will begin with two cohorts, each consisting of 3 male and 3 female participants. The first two cohorts will take a weekly 5mg dose of sirolimus or a weekly 5mg dose of everolimus. Researchers will enroll for both arms of the study concurrently. Participants will be informed that they will be allocated to the next available opening that works with their schedule, which could be either everolimus or rapamycin. The dose can be escalated/de-escalated from the current dose based on the rate of dose limited toxicity (DLT) at the end of the 6-week intervention for each cohort. The 15mg dose will be the highest dose possible in this trial.
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), 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
- NCT05949658
- Sponsor's protocol ID
- 2023-0275
- Other IDs
- 1U01AG081482-01, SMPH/MEDICINE/GER-AD DEV, Protocol Version 4/10/2026
- Status last verified
- Feb 2026
- First submitted
- 26 Jun 2023
- Last updated
- 28 May 2026
- Results posted
- No
- 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 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safer mTOR Inhibition for Human Geroprotection
- ClinicalTrials.gov ID
- NCT05949658
- Acronym / sponsor ID
- 2023-0275
- Conditions
- Aging
- Keywords
- Rapamycin, Rapamycin analog, mTOR, mTOR inhibitor, sirolimus, everolimus, rapamune
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute on Aging (NIA)
- Study start
- 15 May 2024 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 18 Jul 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 RAP PAC is to identify safe and effective weekly dose(s) for the mTOR inhibitors sirolimus and everolimus that intervene on the underlying fundamental biology of aging. Participants who are 55-89 years old that are free of overt chronic diseases will be assigned to either 6 weeks of sirolimus or everolimus (5 mg, 10 mg, or 15 mg once per week). The investigators will complete the everolimus arm first and then subsequently complete the sirolimus arm of the study. Total time on study would be up to 17 weeks to complete baseline and follow up visits.
Detailed description
The mTOR inhibitor rapamycin and rapamycin analogs (rapalogs) extend healthspan and/or lifespan in multiple model systems. However, the risk of adverse events and dose limiting toxicities in humans have thus far precluded the long-term prophylactic use of mTOR inhibitors as a therapy for aging and age-related diseases. The pharmacokinetics and pharmacodynamics (PK/PD) data for mTOR inhibitors in older adults is currently unknown and has prevented the identification of a safe dosage that could maximize health-span extension and minimize adverse effects.
RAP PAC will identify a recommended phase 2 trial dose for sirolimus and everolimus in older men and women by performing a phase 1, dose finding study that evaluates PK/PD, safety and tolerability, and mTOR signaling using conventional as well as novel approaches. Overall, the investigators will pair comprehensive molecular and pharmacologic approaches to evaluate PK/PD in humans and identify dosing regimens that safely inhibit mTOR complex 1 (mTORC1) to intervene in the biology of aging.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The Bayesian Optimal Interval Design (BOIN) will be used to perform a phase I, dose finding trial in healthy older men and women (55-89yrs) for the mTOR inhibitors sirolimus and everolimus. Middle-aged to older adults will be treated with either sirolimus or everolimus for 6 weeks. All participants will take one capsule weekly. This dose escalation trial will begin with two cohorts, each consisting of 3 male and 3 female participants. The first two cohorts will take a weekly 5mg dose of sirolimus or a weekly 5mg dose of everolimus. Researchers will enroll for both arms of the study concurrently. Participants will be informed that they will be allocated to the next available opening that works with their schedule, which could be either everolimus or rapamycin. The dose can be escalated/de-escalated from the current dose based on the rate of dose limited toxicity (DLT) at the end of the 6-week intervention for each cohort. The 15mg dose will be the highest dose possible in this trial.
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | Experimental | Drug: Sirolimus1mg tablets of sirolimus that total the assigned dose |
| Everolimus | Experimental | Drug: Everolimus1mg tablets of everolimus that total the assigned dose |
Who may qualify
- Ages
- 55 to 89 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Middle-age adults 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 telephone
- Ability to take oral medication
Key exclusion criteria (26 listed)
- Heart disease (history, abnormal ECG)
- Cerebrovascular disease (history)
- Cancer or less than 5 years in remission (history)
- Chronic respiratory disease (history, FEV1/FVC < 70, FEV1 < 80% predicted)
- Chronic liver disease (history, abnormal blood liver panel, ALT >104 IU/L, AST >80 IU/L)
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 |
|---|---|---|
| SirolimusAlso: Rapamycin5mg, 10mg, or 15mg once weekly sirolimus | Drug | Sirolimus |
| Everolimus5mg, 10mg, or 15mg once weekly everolimus | Drug | Everolimus |
Primary outcome
Dose Limited Toxicities (DLTs)
Time frame: Through study completion, an average 3 years
A recommended phase 2 dose (RP2D) will be determined through evaluating dose limiting toxicities (DLT), which is defined as ≥Grade 2 adverse event following CTCAE v6.0.
13 secondary outcomes
Time course of drug concentration in blood
Time frame: First dose to 168 hours post dose
Time course of drug concentration in blood
Time frame: First dose to 168 hours post dose
Change in mTOR signaling in blood and muscle
Time frame: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in concentration of metabollites
Time frame: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in concentration of lipid species
Time frame: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in transcriptome
Time frame: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in glucose tolerance
Time frame: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in whole body insulin sensitivity
Time frame: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in glucose variability
Time frame: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in glucose variability
Time frame: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in glucose variability
Time frame: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in glucose variability
Time frame: 0 (pre-intervention) and 6 weeks (post-intervention)
Change in insulin resistance
Time frame: 0 (pre-intervention) and 6 weeks (post-intervention)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
- Individual participant dataSharing planned: Yes
Related trials for Aging
Enrolling by invitationPhase 2
Tirzepatide and Organ-specific Biological Aging
Longevity, Preventive Medicine
Active, not recruiting
Emotional Well-being and Measures of Healthy Aging
Aging, Aging, Healthy
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Active, not recruiting
Vascular Aging and Lp299v Study in Healthy Adults
Vascular Aging
RecruitingObservational study
Amyloid PET Imaging in the Baltimore Longitudinal Study of Aging
Aging
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.
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 1 study testing Sirolimus and Everolimus in people with Aging, 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 8 inclusion and 26 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: looking for participants now, as of the sponsor's last update on 28 May 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Brittany Grasso (608-263-2386, rap_pac@medicine.wisc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limited Toxicities (DLTs) (time frame: Through study completion, an average 3 years). 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 28 May 2026.