Short Term Sirolimus Treatment and MRI of the Brain and Lungs

Launched by UNIVERSITY OF MISSOURI-COLUMBIA · May 19, 2022

Keywords

ClinConnect Summary

This clinical trial is looking at how a medication called sirolimus may help improve blood flow in the brain, which could be important for people at risk of Alzheimer’s disease. Alzheimer's is a serious brain condition that currently has no cure, and sirolimus is already approved by the FDA for other uses. The study aims to see if short-term treatment with sirolimus can change brain blood flow as seen on MRI scans in both healthy volunteers and those with a genetic risk for Alzheimer’s.

To participate in the trial, you need to be between 45 and 65 years old and have a good score on a cognitive test, indicating you do not have memory problems. You may be eligible if you have a specific genetic marker associated with Alzheimer's, or if you do not carry this marker at all. Throughout the study, participants will receive the sirolimus treatment and undergo MRI scans to measure its effects on blood flow in the brain. It’s important to note that there are several health conditions and factors that may exclude someone from participating, such as having a history of dementia or certain medical issues. If you think you might be eligible or are interested in learning more, you should reach out to the study team for further details.

Gender

ALL

Eligibility criteria

• Part I:
• 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
• Part II:
• The inclusion and exclusion criteria for Part I apply to Part II with the addition of the following:
• Exclusion Criteria:
• • 1. Baseline oxygen requirement
• • 2. Blood oxygen saturation of 90% or less than as measured by pulse oximetry on the day of imaging
• • 3. FEV1 percent predicted less than 25%
• • 4. Claustrophobia, inner ear implants, aneurysm or other surgical clips, metal foreign bodies in the eye, pacemaker or other contraindication to MR scanning. Subjects with any implanted device that cannot be verified as MRI compliant will be excluded
• • 5. Chest circumference greater than that of the xenon-129 MR coil. The circumference of the coil is approximately 42 inches
• • 6. History of congenital cardiac disease or history of apneic episodes
• • 7. Inability to understand simple instructions or to hold still for approximately 10 seconds
• • 8. History of respiratory infection within 2 weeks prior to the MR scan