Everolimus Aging Study

• Status: Recruiting
• Trial end date: 2026-12-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Wisconsin, Madison
• Collaborator: National Institute on Aging (NIA)
• Treatments: Everolimus

Criteria

Inclusion Criteria: Adults aged 55-80 years old

• 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.

Inclusion Criteria: Younger Adults aged 18-35 (No intervention)

• Free overt chronic disease

Exclusion Criteria:

• 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

• Problems with bleeding, on medication that prolongs bleeding time (if subject cannot safely stop prior to biopsy)

• Taking strong or moderate CYP3A4 and/or P-glycoprotein (PgP) inhibitors

• Taking strong CYP3A4 activators

• 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

• 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