Effects of Donepezil HCL on Task-Activated fMRI Brain Activation in Healthy Older Adults at Genetic Risk for Alzheimer's Disease

Phase 4

Completed

• Conditions: Genetic Risk for Alzheimer's Disease
• Interventions: Drug: donepezil HCL; Drug: Placebo

• Registration Number: NCT02087865
• Lead Sponsor: The Cleveland Clinic

Brief Summary

This study examines the sensitivity of functional MRI to detect brain changes caused by donepezil HCL (a cholinesterase inhibitor) in healthy older adults at genetic risk for Alzheimer's Disease.

Detailed Description

This 24-week study will examine the sensitivity of functional MRI to detect brain changes caused by donepezil HCL (a cholinesterase inhibitor) in healthy older adults at genetic risk for Alzheimer's Disease. Participants with a family history of Alzheimer's Disease will be eligible for this study. Participants without a family history of AD will also be enrolled to serve as a control group.

Study Timeline

• Study First Submitted: 2014-03-07
• Study First Submitted QC: 2014-03-13
• Study First Posted: 2014-03-14
• Study Start: 2014-05
• Primary Completion: 2021-12-20
• Study Completion: 2021-12-20
• Results First Submitted: 2023-06-29
• Status Verified: 2023-08
• Results First Submitted QC: 2023-08-08
• Last Update Submitted: 2023-08-08
• Results First Posted: 2023-08-30
• Last Update Posted: 2023-08-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 89

Inclusion Criteria

• Normal general cognitive function
• High Risk Group Only: Family history (1st degree relative) of AD
• Low Risk Group Only: No family history (1st or 2nd degree relative) of AD
• Visual and auditory acuity adequate for neuropsychological testing

Exclusion Criteria

• Current or past history of
• neurological illnesses/conditions
• head trauma with significant loss of consciousness
• medical illnesses/conditions that may affect brain function
• severe psychiatric disorder
• substance abuse
• unstable or severe cardiovascular disease or asthmatic condition
• history of stroke or transient ischemic attack

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Donepezil HCL	donepezil HCL	Participants will receive 5mg of donepezil HCL for 4 weeks and then 10mg of donepezil HCL for 20 weeks.
Placebo	Placebo	Participants will receive placebo for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Left Hippocampus BOLD Signal at 24 Weeks, Adjusted for Baseline Left Hippocampus BOLD Signal	Baseline and 24 Weeks	Left hippocampus BOLD signal at 24 weeks, adjusting for baseline left hippocampus BOLD signal.
Change in BOLD Response From Baseline to 24 Weeks During Functional Magnetic Resonance Imaging - Left Posterior Cingulate BOLD Signal at 24 Weeks, Adjusting for Baseline Left Posterior Cingulate BOLD	Baseline and 24 Weeks	Changes from baseline to 24 weeks follow-up fMRI - Left posterior cingulate BOLD signal at 24 weeks, adjusting for baseline left posterior cingulate BOLD signal.
Right Hippocampus BOLD Signal at 24 Weeks, Adjusted for Baseline Left Hippocampus BOLD Signal	Baseline and 24 Weeks	Right hippocampus BOLD signal at 24 weeks, adjusting for baseline left hippocampus BOLD signal.

Secondary Outcome Measures

Name	Time	Method
Processing Speed Test (PST) at 24 Weeks, Adjusted for Baseline PST Scores	Baseline and 24 Weeks	Processing speed test (PST) at 24 weeks, adjusting for baseline PST scores. The PST has a minimum of 0 and no upper limit/maximum since it is the number of correct items in 2 minutes. A higher score means better outcome.
Brief Visuospatial Memory Test (BVMT) Learning Scores at 24 Weeks, Adjusted for Baseline BVMT Learning Scores	Baseline and 24 Weeks	Brief Visuospatial Memory Test (BVMT) learning scores at 24 weeks, adjusted for baseline BVMT learning scores. The BVMT-R total scare has a minimum of 0 and a maximum of 36 correct items (12 per trial x 3 trials). A higher score means better outcomes.
Neuropsychological Testing Scores - Rey Auditory Verbal Learning Test (RAVLT) Sum of Trials (1-5) at 24 Weeks, Adjusted for Baseline RAVLT Score	Baseline and 24 Weeks	Rey Auditory Verbal Learning Test (RAVLT) (Sum of Trials 1-5) , adjusting for baseline RAVLT (Sum of Trials 1-5) score. The RAVLT total score has a minimum of 0 and a maximum of 75 correct items (15 per trial x 5 trials). A higher score means better outcomes.
Left Hippocampus Volume (MRI) at 24 Weeks, Adjusted for Baseline Left Hippocampus Volume	Baseline and 24 Weeks	Left hippocampus volume (MRI) at 24 weeks, adjusting for baseline left hippocampus volume
Right Hippocampus Volume (MRI) at 24 Weeks, Adjusted for Baseline Right Hippocampus Volume	Baseline and 24 Weeks	Right hippocampus volume (MRI) at 24 weeks, adjusting for baseline right hippocampus volume

Trial Locations

Locations (1)

Cleveland Clinic Center for Brain Health; 🇺🇸 Cleveland, Ohio, United States