RESTOR: PK/PD mTORi Inhibition in Older Adults

Launched by THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO · Oct 22, 2024

Keywords

ClinConnect Summary

The RESTOR trial is a study that aims to understand how certain medications, known as mTOR inhibitors, can help older adults stay healthier as they age. As people get older, their bodies can undergo changes that may lead to various health issues, such as heart disease or Alzheimer’s disease. This study will test two specific drugs, Rapamycin and Everolimus, to find the right dosage that can safely mimic the levels of these medications seen in younger individuals. The researchers are particularly interested in how these dosages may differ between men and women, so they want participants of all genders.

To be eligible for the trial, participants should be between 65 and 90 years old, in good health, and living independently within 30 miles of the study site. They also need to be fully vaccinated against COVID-19. Participants can expect to undergo regular health assessments during the study and must agree to follow certain lifestyle guidelines. It's important to note that individuals with specific health conditions, such as active cancer or severe heart disease, will not be able to participate. If you or someone you know fits the eligibility criteria and is interested in contributing to this important research, please keep an eye out for when the study begins recruiting participants.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• Older Cohort Sub-study 2 (AIM 1) and Sub-study 3 (AIM 2):
• • 1. Age ≥65 to 90 years
• • 2. Men and women
• • 3. In good health with all medical problems stable.
• • 4. Community-dwelling
• • 5. Fully vaccinated against COVID19
• • 6. Living within 30 miles of UTHSA (to facilitate home visits)
• • 7. Agreement to adhere to Lifestyle Considerations throughout study duration.
• • 8. Ability of participant to understand and the willingness to sign a written informed consent document.
• Exclusion Criteria:
• Older Cohort Sub-study 2 (AIM 1) and Sub-study 3 (AIM 2):
• • 1. Resident of nursing home or long-term care facility
• • 2. Subjects with diabetes or currently taking glucose lowering medications
• • 3. History of moderate-severe heart disease (New York Heart Classification greater than grade II) or pulmonary disease (dyspnea on exertion upon climbing one flight of stairs or less; abnormal breath sounds on auscultation); Moderate to severe valvular heart disease
• • 4. Active cancer or history of cancer treatment within the last 5 years
• • 5. Chronic inflammatory condition, autoimmune disease, or infectious processes (e.g., active tuberculosis, HIV, rheumatoid arthritis, systemic lupus erythematosus, acute or chronic hepatitis B or C)
• • 6. History of a coagulopathy or any medical condition requiring anticoagulation (except low dose ASA)
• • 7. Renal insufficiency with an estimated glomerular filtration rate of \<30ml/min
• • 8. Uncontrolled hypercholesterolemia \>350mg/dl or uncontrolled hypertriglyceridemia \>500mg/dl
• • 9. Anemia or abnormal blood cell counts: hemoglobin level \<9.0g.dl; white blood count \<3500/mm3; neutrophil count \<2000/ mm3; platelet count \<125,000/mm3
• • 10. History of skin ulcers or poor wound healing
• • 11. Active tobacco use (within 6 months)
• • 12. Diagnosis of any disabling neurologic disease such as Parkinson's Disease, Amyotrophic Lateral Sclerosis, multiple sclerosis, cerebrovascular accident with residual deficits (muscle weakness or gait disorder), severe neuropathy, diagnosis of dementia or Montreal Cognitive Assessment (MOCA) score \<21 at the time of screening visit, cognitive impairment due to any reason such that the patient is unable to provide informed consent
• • 13. Liver disease
• • 14. Systemic treatment with an immunosuppressant (prednisone, etc.) within the year prior to enrollment
• • 15. Treatment with drugs known to affect cytochrome P450 (CYP3A4 and CYP3A5), i.e., diltiazem, erythromycin.
• • 16. Patients with history of recent (within 6 months) myocardial infarction or active coronary disease
• • 17. Patients with history of recent (within 6 months) intestinal disorders
• • 18. History of severe head trauma, brain injury, brain surgery, inflammation of the brain, or history of seizures
• • 19. History of Long-Covid (PASC)
• • 20. Acute Covid19 or Covid19 infection within the last 6 months
• • 21. Unwilling to forgo grapefruit juice consumption.
• • 22. Participation in mTORi study within the prior year. (Note: participants in AIM 1 will be excluded from participating in AIM 2 of the proposed trial.)
• • 23. Allergic to RAPA or EVERO
• • 24. Allergic to lidocaine
• • 25. Recreational drug use
• • 26. Donated blood over a two-month period prior to study initiation.
• • 27. Currently using cannabidiol (CBD) or tetrahydrocannabinol (THC) or any preparation contained these, or related, substances.
• • 28. Currently using hormone replacement or modulating therapies.