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

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.

Study Overview

• Status: Completed
• Conditions: Genetic Risk for Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo; Drug: donepezil HCL

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 Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Center for Brain Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Donepezil HCL; Participants will receive 5mg of donepezil HCL for 4 weeks and then 10mg of donepezil HCL for 20 weeks.	Drug: donepezil HCL
Placebo Comparator: Placebo; Participants will receive placebo for 24 weeks.	Drug: Placebo
No Intervention: Control Group; Participants without a family history of AD will undergo the study evaluations but will not receive any study drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Baseline and 24 Weeks
Left Hippocampus BOLD Signal at 24 Weeks, Adjusted for Baseline Left Hippocampus BOLD Signal	Left hippocampus BOLD signal at 24 weeks, adjusting for baseline left hippocampus BOLD signal.	Baseline and 24 Weeks
Right Hippocampus BOLD Signal at 24 Weeks, Adjusted for Baseline Left Hippocampus BOLD Signal	Right hippocampus BOLD signal at 24 weeks, adjusting for baseline left hippocampus BOLD signal.	Baseline and 24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropsychological Testing Scores - Rey Auditory Verbal Learning Test (RAVLT) Sum of Trials (1-5) at 24 Weeks, Adjusted for Baseline RAVLT Score	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.	Baseline and 24 Weeks
Left Hippocampus Volume (MRI) at 24 Weeks, Adjusted for Baseline Left Hippocampus Volume	Left hippocampus volume (MRI) at 24 weeks, adjusting for baseline left hippocampus volume	Baseline and 24 Weeks
Right Hippocampus Volume (MRI) at 24 Weeks, Adjusted for Baseline Right Hippocampus Volume	Right hippocampus volume (MRI) at 24 weeks, adjusting for baseline right hippocampus volume	Baseline and 24 Weeks
Brief Visuospatial Memory Test (BVMT) Learning Scores at 24 Weeks, Adjusted for Baseline BVMT Learning Scores	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.	Baseline and 24 Weeks
Processing Speed Test (PST) at 24 Weeks, Adjusted for Baseline PST Scores	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.	Baseline and 24 Weeks

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Stephen M Rao, Ph.D., The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): December 20, 2021
• Study Completion (Actual): December 20, 2021

Study Registration Dates

• First Submitted: March 7, 2014
• First Submitted That Met QC Criteria: March 13, 2014
• First Posted (Estimated): March 14, 2014

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 8, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: 14-227