Investigating the effects of mTOR inhibitors on aging
Safer mTOR Inhibition for Human Geroprotection
This study is testing if weekly doses of two medications, sirolimus and everolimus, can help older adults aged 55-89 improve their health as they age.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 72 (estimated) |
| Ages | 55 Years to 89 Years |
| Sex | All |
| Sponsor | University of Wisconsin, Madison Academic / other |
| Drugs / interventions | methotrexate, prednisone |
| Locations | 1 site (Madison, Wisconsin) |
| Trial ID | NCT05949658 on ClinicalTrials.gov |
What this trial studies
The RAP PAC study aims to determine safe and effective weekly doses of the mTOR inhibitors sirolimus and everolimus to address the biology of aging in adults aged 55-89. Participants will be assigned to receive either sirolimus or everolimus for six weeks, with a total study duration of up to 17 weeks for baseline and follow-up visits. The study will evaluate pharmacokinetics, pharmacodynamics, safety, and tolerability, using both conventional and novel approaches to assess mTOR signaling. This phase 1 trial seeks to identify optimal dosing regimens that can maximize healthspan while minimizing adverse effects.
Who should consider this trial
Good fit: Ideal candidates are middle-aged adults aged 55-89 who are free of overt chronic diseases.
Not a fit: Patients with a history of heart disease, cerebrovascular disease, cancer, chronic respiratory disease, chronic liver disease, or diabetes may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could lead to improved healthspan and longevity for older adults through safe mTOR inhibition.
How similar studies have performed: While mTOR inhibitors have shown promise in model systems, this specific approach in older adults is novel and has not been extensively tested.
Eligibility criteria
Show full inclusion / exclusion criteria
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 CYP3A4 activators such as phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital * 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 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
Where this trial is running
Madison, Wisconsin
- University of Wisconsin — Madison, Wisconsin, United States (Recruiting)
Study contacts
- Principal investigator: Adam Konopka, PhD — University of Wisconsin, Madison
- Study coordinator: Brittany Grasso
- Email: rap_pac@medicine.wisc.edu
- Phone: 608-263-2386
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.