Recruiting
Phase 1

Rapalog

Sponsor:

University of Wisconsin, Madison

Code:

NCT05949658

Conditions

Aging

Eligibility Criteria

Sex: All

Age: 55 - 70+

Healthy Volunteers: Accepted

Interventions

Sirolimus

Everolimus

Study Details

Brief 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. 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.

Conditions

Aging

Study ID

NCT05949658

Start date

May 15, 2024

Status verified date

Feb, 2026

Completion date

Dec, 2028

Anticipated

Primary completion date

Mar, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 55 - 70+

Healthy Volunteers: Accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.)
  • 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

Study Design

Enrollment

72 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Sirolimus

1mg tablets of sirolimus that total the assigned dose

experimental: Everolimus

1mg tablets of everolimus that total the assigned dose

Interventions

Sirolimus

5mg, 10mg, or 15mg once weekly sirolimus

Everolimus

5mg, 10mg, or 15mg once weekly everolimus

Primary outcome measure

  • Dose Limited Toxicities (DLTs) [ Time Frame: Through study completion, an average 3 years ]

Central Contacts and Locations

Central contacts

Brittany Grasso

608-263-2386rap_pac@medicine.wisc.edu

Locations

University of Wisconsin

Recruiting

Madison, Wisconsin, United States, 53705

Principal Investigator:

Adam Konopka, PhD

More Information

Sponsor

University of Wisconsin, Madison

Last update posted

May 28, 2026

Last verified

Feb, 2026

Keywords

  • Rapamycin
  • Rapamycin analog
  • mTOR
  • mTOR inhibitor
  • sirolimus
  • everolimus
  • rapamune

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of Wisconsin, Madison on 2026-05-28.