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Short Term Sirolimus Treatment and MRI of the Brain

Sponsor
University of Missouri-Columbia (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05386914
Collaborator
(none)
105
Enrollment
1
Location
2
Arms
17
Anticipated Duration (Months)
6.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
105 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Investigator)
Masking Description:
The member of the study team carrying out the MRI imaging and image analysis will be blinded to the APOE genotype of the subject, subject's family history, and treatment category.
Primary Purpose:
Basic Science
Official Title:
Short Term Apolipoprotein E (ApoE)-Dependent Cerebral Blood Flow Response to Sirolimus in Cognitively Normal Adults
Anticipated Study Start Date :
Jul 1, 2022
Anticipated Primary Completion Date :
Jul 1, 2023
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. Change in Cerebral blood flow as measured on MRI after 4 weeks of Sirolimus [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

Eligibility Criteria

Criteria

Ages Eligible for Study:
45 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
    1. Age 45-65 y/o
    1. Male or female, all ethnic groups
    1. Montreal Cognitive Assessment (MoCA) score greater than or equal to 26
    1. Clinical Dementia Rating (CDR) Staging Instrument = 0
    1. Carrier Cohort: APOE4 homozygous or heterozygous
    1. Non-Carrier cohort: no APOE4 gene identified
Exclusion Criteria:
    1. Diagnosis of mild cognitive impairment (MCI) or dementia, including Alzheimer's disease
    1. BMI ≥35 (based on MRI feasibility)
    1. Diabetes (HBA1c≥6.5% or antidiabetic medications)
    1. History of skin ulcers or poor wound healing
    1. 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)
    1. Use of anti-platelet or anti-coagulant medications other than aspirin
    1. Current medications that affect cytochrome P450 3A4 (CYP3A4)
    1. Immunosuppressant therapy within the last year
    1. Chemotherapy or radiation treatment within the last year
    1. Current or chronic history of liver or kidney disease or known hepatic or biliary abnormalities
    1. Untreated hypertriglyceridemia (fasting triglycerides < 300 mg/dl)
    1. Current or chronic significant history of pulmonary disease
    1. Chronic heart failure
    1. Pregnancy or lactation
    1. Recent history (past six months) of myocardial infarction, active coronary artery disease, intestinal disorders, stroke, or transient ischemic attack
    1. 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

    1. History of, or MRI, or CT positive for, any space occupying brain lesion, including mass effect or abnormal intracranial pressure
    1. Organ transplant recipients
    1. History of Stroke
    1. History of ruptured intracranial aneurysm
    1. Any condition for which a MRI procedure is contraindicated. Some examples include: metallic material in the body, such as pacemakers, metallic clips, etc.
    1. Likelihood of claustrophobia

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Missouri-Columbia Columbia Missouri United States 65212

Sponsors and Collaborators

  • University of Missouri-Columbia

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Ai-Ling Lin, PhD, Professor, University of Missouri-Columbia
ClinicalTrials.gov Identifier:
NCT05386914
Other Study ID Numbers:
  • 2091042
First Posted:
May 23, 2022
Last Update Posted:
May 23, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Disease Susceptibility
Genetic Predisposition to Disease
Sirolimus

Study Results

No Results Posted as of May 23, 2022