Sirolimus treatment and MRI imaging of the brain and lungs

Short Term Apolipoprotein E (ApoE)-Dependent Cerebral Blood Flow and Lung Perfusion Response to Sirolimus in Cognitively Normal Adults

This study is testing if the medication sirolimus can improve blood flow in the brains and lungs of people with a specific genetic risk for Alzheimer's disease.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 205 (estimated)
• Ages: 45 Years to 65 Years
• Sex: All
• Sponsor: University of Missouri-Columbia (other)
• Drugs / interventions: Chemotherapy, radiation
• Locations: 1 site (Columbia, Missouri)
• Trial ID: NCT05386914 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of sirolimus, an FDA-approved medication, on improving blood flow to the brain in individuals with and without a genetic predisposition to Alzheimer's disease. The first part of the study has been completed, focusing on participants aged 45-65, while the ongoing second part aims to enroll only APOE4 carriers to further explore the drug's impact on lung perfusion using hyperpolarized xenon-129 gas MRI. This non-invasive imaging technique allows for direct visualization of blood flow in the brain and lungs. The study seeks to understand the connection between brain vascular health and genetic factors related to Alzheimer's disease.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 45-65 who are carriers of the APOE4 gene.

Not a fit: Patients diagnosed with mild cognitive impairment or dementia, including Alzheimer's disease, will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment options for individuals at risk of Alzheimer's disease by enhancing brain blood flow.

How similar studies have performed: While this approach is novel in its specific application, similar studies exploring sirolimus and brain health have shown promising results.

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

Where this trial is running

Columbia, Missouri

• University of Missouri-Columbia — Columbia, Missouri, United States (RECRUITING)

Study contacts

• Principal investigator: Ai-Ling Lin, PhD — University of Missouri-Columbia
• Study coordinator: Jessica Call

Conditions: Genetic Predisposition to Disease, Healthy Volunteers