RECRUITING

Rapalog Pharmacology (RAP PAC) Study

Conditions

Aging Rapamycin Rapamycin analog mTOR mTOR inhibitor sirolimus everolimus rapamune

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Safer mTOR Inhibition for Human Geroprotection

Quick Facts

Study Start:2024-05-15

Study Completion:2028-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05949658

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:55 Years to 89 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Study Contact

Brittany Grasso

CONTACT

608-263-2386

rap_pac@medicine.wisc.edu

Principal Investigator

Adam Konopka, PhD

PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Study Locations (Sites)

University of Wisconsin

Madison, Wisconsin, 53705

United States

Collaborators and Investigators

Sponsor: University of Wisconsin, Madison

Adam Konopka, PhD, PRINCIPAL_INVESTIGATOR, University of Wisconsin, Madison

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-05-15

Study Completion Date2028-12

Study Record Updates

Study Start Date2024-05-15

Study Completion Date2028-12

Terms related to this study

Keywords Provided by Researchers

Rapamycin
Rapamycin analog
mTOR
mTOR inhibitor
sirolimus
everolimus
rapamune

Additional Relevant MeSH Terms

Aging