Short Term Sirolimus Treatment and MRI of the Brain

University of Missouri (MU)

Status and phase: Enrolling; Phase 1

Conditions: Healthy Volunteers; Genetic Predisposition to Disease

Treatments: Drug: Sirolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT05386914

2091042

Details and patient eligibility

About

Alzheimer's disease is a devastating neurodegenerative disease characterized by accumulation of clumps (also called plaques) and bundles of fibers (also called tangles) in the brain, for which there is currently no cure. Sirolimus is an FDA-approved medication which may improve the blood flow to the brain. This study is designed to see if sirolimus treatment improves MRI blood flow to the brain in individuals with and without a genetic predisposition to Alzheimer's disease.

Enrollment: 105 estimated patients

Sex: All

Ages: 45 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 1. Age 45-65 y/o
• 2. Male or female, all ethnic groups
• 3. Montreal Cognitive Assessment (MoCA) score greater than or equal to 26
• 4. Clinical Dementia Rating (CDR) Staging Instrument = 0
• 5. Carrier Cohort: APOE4 homozygous or heterozygous
• 6. Non-Carrier cohort: no APOE4 gene identified

Exclusion criteria

• 1. Diagnosis of mild cognitive impairment (MCI) or dementia, including Alzheimer's disease
• 2. BMI ≥35 (based on MRI feasibility)
• 3. Diabetes (HBA1c≥6.5% or antidiabetic medications)
• 4. History of skin ulcers or poor wound healing
• 5. Current tobacco or illicit drug use or alcohol abuse (defined as ≥4 per day or ≥14 per week for men and ≥3 per day or ≥7 per week for women) (Per NIAAA guidelines)
• 6. Use of anti-platelet or anti-coagulant medications other than aspirin
• 7. Current medications that affect cytochrome P450 3A4 (CYP3A4)
• 8. Immunosuppressant therapy within the last year
• 9. Chemotherapy or radiation treatment within the last year
• 10. Current or chronic history of liver or kidney disease or known hepatic or biliary abnormalities
• 11. Untreated hypertriglyceridemia (fasting triglycerides < 300 mg/dl)
• 12. Current or chronic significant history of pulmonary disease
• 13. Chronic heart failure
• 14. Pregnancy or lactation
• 15. Recent history (past six months) of myocardial infarction, active coronary artery disease, intestinal disorders, stroke, or transient ischemic attack
• 16. Poorly controlled blood pressure (systolic BP>160 or diastolic BP>100 mmHg)
• 17.Active inflammatory, Coronavirus (COVID-19), autoimmune, infectious, hepatic, gastrointestinal, malignant, and/or severe mental illness
• 18. History of, or MRI, or CT positive for, any space occupying brain lesion, including mass effect or abnormal intracranial pressure
• 19. Organ transplant recipients
• 20. History of Stroke
• 21. History of ruptured intracranial aneurysm
• 22. Any condition for which a MRI procedure is contraindicated. Some examples include: metallic material in the body, such as pacemakers, metallic clips, etc.
• 23. Likelihood of claustrophobia

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

105 participants in 2 patient groups

Carrier APOE4

Experimental group

Treatment:

Drug: Sirolimus

Non-Carrier APOE4

Other group

Treatment:

Drug: Sirolimus