Everolimus Aging Study

Phase 2

Recruiting

• Conditions: Aging; Insulin Resistance

• Registration Number: NCT05835999
• Lead Sponsor: University of Wisconsin, Madison

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-4-3
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

Inclusion Criteria: Adults aged 55-80 years old<br><br> - Free of overt chronic disease<br><br> - Willing to provide informed consent<br><br> - Willing to comply with all study procedures and be available for the duration of the<br> study<br><br> - Able to use and be contacted by the telephone<br><br> - Ability to take oral medication<br><br> - Insulin Resistant defined by HOMA-IR greater than or equal to 1.5 or prediabetic<br> defined as:<br><br> - impaired fasting glucose (100-125 mg/dL)<br><br> - HbA1c (5.7-6.4 percent)<br><br> - glucose 2 hours after a 75 gram oral glucose tolerance test (140-199 mg/dL)<br><br> - previous diagnosis of prediabetes in the past year<br><br> - Not planning to change diet or physical activity status<br><br> - Adequate organ function as indicated by standard laboratory tests: hematology<br> (complete blood count), clinical chemistry and urinalysis<br><br> - Females of childbearing potential must have a negative urine pregnancy test before<br> DEXA and before the oral glucose tolerance test (OGTT). A female of child-bearing<br> potential is any woman (regardless of sexual orientation, having undergone a tubal<br> ligation, or remaining celibate by choice) who meets the following criteria:<br><br> - Has not undergone a hysterectomy or bilateral oophorectomy; or<br><br> - Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,<br> has had menses at any time in the preceding 12 consecutive months)<br><br> - Women of childbearing potential in sexual relationships with men must use an<br> acceptable method of contraception from 30 days prior to enrollment until 4 weeks<br> after completing study visits. Males must agree to avoid impregnation of women<br> during and for four weeks after completing study visits through use of an acceptable<br> method of contraception.<br><br> - Note: Includes, but is not limited to, barrier with additional spermicidal foam<br> or jelly, intrauterine device, hormonal contraception (started at least 30 days<br> prior to study enrollment), intercourse with men who underwent vasectomy.<br><br>Inclusion Criteria: Younger Adults aged 18-35 (No intervention)<br><br> - Free overt chronic disease<br><br>Exclusion Criteria:<br><br> - Pregnancy or breastfeeding<br><br> - Heart disease<br><br> - Cerebrovascular disease<br><br> - Cancer or less than 5 years in remission<br><br> - Chronic respiratory disease<br><br> - Chronic liver disease<br><br> - Diabetes<br><br> - Alzheimer's<br><br> - Chronic kidney disease<br><br> - Problems with bleeding, on medication that prolongs bleeding time (if subject cannot<br> safely stop prior to biopsy)<br><br> - Taking azathioprine (Imuran), cyclosporine (Gengraf, Neoral, Sandimmune),<br> dexamethasone (Decadron, Dexpak), methotrexate (Rheumatrex, Trexall), prednisolone<br> (Orapred, Pediapred, Prelone), prednisone (Sterapred), sirolimus (Rapamune), and<br> tacrolimus (Prograf) or other medications proposed to lower the immune system. Daily<br> use of high potency topical corticosteroids used on greater than or equal to 10% of<br> body surface area will not be eligible. Nasal sprays or inhaled corticosteroids will<br> be reviewed on a case-by-case basis.<br><br> - Taking strong or moderate CYP3A4 and/or P-glycoprotein (PgP) inhibitors<br><br> - Taking strong CYP3A4 activators<br><br> - Taking daily NSAIDs with the exception of baby asprin (81 mg)<br><br> - Subjects who are not willing to restrict the use of grapefruit, grapefruit juice,<br> and other foods that are known to inhibit cytochrome P450 and PgP activity and may<br> increase everolimus exposures and should be avoided during treatment<br><br> - Subjects who are not willing to restrict the use of St. John's Wort (Hypericum<br> perforatum) because it may decrease everolimus exposure unpredictably<br><br> - Subjects who are not willing to avoid blood donations 8 weeks prior to the first<br> visit and 8 weeks after the last visit<br><br> - Contraindications with MRI which could include metal on your body<br><br> - Low white-blood cell count (<4,000 cell/µL)<br><br> - History of stomatitis or ulcers in the mouth<br><br> - Those on glucose lowering drugs<br><br> - Participating in intensive exercise training program (high to moderate intensity<br> exercise greater than 150 minutes per week) or planning to start new exercise<br> program during study period<br><br> - Tobacco use<br><br> - Allergies to lidocaine or everolimus<br><br> - Subjects currently enrolled in other clinical trials. Subjects may be eligible after<br> a washout period that will be reviewed on a case by case basis.<br><br> - Individuals with limited English proficiency<br><br> - Subjects who are planning to have elective surgery 12 weeks prior to or during the<br> intervention

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Metabolic Function: Change in peripheral insulin sensitivity

Secondary Outcome Measures

Name	Time	Method
Cardiac Function: Change in fractional shortening velocity;Cognitive Function: Change in cerebral blood flow;Safety: Number of Participants with Adverse Events;Safety: Change in concentration of blood metabolites/enzymes;Safety: Changes in concentration of blood lipids;Safety: Changes in number of blood cells;Safety: Changes in HbA1c (%);Safety: Changes in concentration of insulin;mTOR signaling: Change in phosphorylation of downstream targets of mTOR complex 1 and complex 2 as assessed by immunoblotting and immunoprecipitation.