Short Term Sirolimus Treatment and MRI of the Brain

March 12, 2024 updated by: Ai-Ling Lin, PhD, University of Missouri-Columbia

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

105

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Missouri
      • Columbia, Missouri, United States, 65212
        • Recruiting
        • University of Missouri-Columbia
        • Contact:
        • Contact:
        • Principal Investigator:
          • Ai-Ling Lin, PhD
        • Sub-Investigator:
          • David Beversdorf, MD
        • Sub-Investigator:
          • Altes Talissa, MD

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.

Eligibility Criteria

Ages Eligible for Study

45 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Carrier APOE4
Drug: Sirolimus
1 mg of Sirolimus taken orally once a day for 4 weeks.
Other: Non-Carrier APOE4
Drug: Sirolimus
1 mg of Sirolimus taken orally once a day for 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Cerebral blood flow as measured on MRI after 4 weeks of Sirolimus
Time Frame: Assessed at Visit 2 immediately before starting sirolimus and Visit 4 after 4 weeks of continuous sirolimus
Rate of blood perfusion expressed as mL/g/min in hippocampus
Assessed at Visit 2 immediately before starting sirolimus and Visit 4 after 4 weeks of continuous sirolimus

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Missouri-Columbia

Investigators

  • Principal Investigator: Ai-Ling Lin, PhD, University of Missouri-Columbia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2023

Primary Completion (Estimated)

July 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

May 16, 2022

First Submitted That Met QC Criteria

May 19, 2022

First Posted (Actual)

May 23, 2022

Study Record Updates

Last Update Posted (Actual)

March 13, 2024

Last Update Submitted That Met QC Criteria

March 12, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2091042

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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