Short Term Sirolimus Treatment and MRI of the Brain and Lungs

Description

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. Part I: 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. Part I of this study is complete and no longer enrolling participants. Part II: Ongoing research will expand the genetic predisposition cohort and further explore the drug's impact on the lung perfusion via hyperpolarized xenon-129 gas MRI and the brain-vascular connection. Only subjects who are APOE4 carriers will be enrolled in Part II. Hyperpolarized xenon-129 gas MRI is a non-invasive technique in which a subject inhales a bolus of hyperpolarized xenon-129 gas which can be directly imaged by the MRI as it physiologically distributes itself throughout the lung interior and within tissue and red blood cells. It thus allows for direct imaging and quantification of regional lung function: ventilation, gas-exchange, and perfusion. The relationship between pulmonary vascular function and brain perfusion is largely unstudied. We hope to investigate the relationship between pulmonary vascular function and cerebral blood flow by quantifying both lung and brain perfusion before and after the administration of Sirolimus.

Conditions

Genetic Predisposition to Disease, Healthy Volunteers

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Study Overview

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Study Details

Study overview

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. Part I: 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. Part I of this study is complete and no longer enrolling participants. Part II: Ongoing research will expand the genetic predisposition cohort and further explore the drug's impact on the lung perfusion via hyperpolarized xenon-129 gas MRI and the brain-vascular connection. Only subjects who are APOE4 carriers will be enrolled in Part II. Hyperpolarized xenon-129 gas MRI is a non-invasive technique in which a subject inhales a bolus of hyperpolarized xenon-129 gas which can be directly imaged by the MRI as it physiologically distributes itself throughout the lung interior and within tissue and red blood cells. It thus allows for direct imaging and quantification of regional lung function: ventilation, gas-exchange, and perfusion. The relationship between pulmonary vascular function and brain perfusion is largely unstudied. We hope to investigate the relationship between pulmonary vascular function and cerebral blood flow by quantifying both lung and brain perfusion before and after the administration of Sirolimus.

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

Short Term Sirolimus Treatment and MRI of the Brain and Lungs

Condition
Genetic Predisposition to Disease
Intervention / Treatment

-

Contacts and Locations

Columbia

University of Missouri-Columbia, Columbia, Missouri, United States, 65212

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility 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
  • * 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

Ages Eligible for Study

45 Years to 65 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

Yes

Collaborators and Investigators

University of Missouri-Columbia,

Ai-Ling Lin, PhD, PRINCIPAL_INVESTIGATOR, University of Missouri-Columbia

Study Record Dates

2027-12