ACTIVE_NOT_RECRUITING

Everolimus Aging Study

Conditions

Aging Insulin Resistance rapamycin rapamycin analog mTOR everolimus

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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 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.

Official Title

Clinical Evaluation of mTORC1 Inhibition for Geroprotection

Quick Facts

Study Start:2023-03-24

Study Completion:2026-09

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05835999

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:18 Years to 80 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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: * 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.	* Pregnancy or breastfeeding * Heart disease * Cerebrovascular disease * Cancer or less than 5 years in remission * Chronic respiratory disease * Chronic liver disease * 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 (\<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 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

* 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:
* 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.

* Pregnancy or breastfeeding
* Heart disease
* Cerebrovascular disease
* Cancer or less than 5 years in remission
* Chronic respiratory disease
* Chronic liver disease
* 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 (\<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 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

Principal Investigator

Adam Konopka, PhD

PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Study Locations (Sites)

University of Wisconsin-Madison

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 Date2023-03-24

Study Completion Date2026-09

Study Record Updates

Study Start Date2023-03-24

Study Completion Date2026-09

Terms related to this study

Keywords Provided by Researchers

rapamycin
rapamycin analog
mTOR
everolimus

Additional Relevant MeSH Terms

Aging
Insulin Resistance