Study of Exelon Transdermal Patch in Amnestic Mild Cognitive Impairment Patients

Study Overview
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Brief Summary
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The goal of this project is to determine if task-activated fMRI is sensitive to the central cholinergic deficit associated with Mild Cognitive Impairment.

Detailed Description
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Clinical studies suggest that cholinesterase inhibitors (ChEIs) exert a cognitive benefit with chronic use among MCI and AD patients. Some studies also demonstrate a slight treatment benefit for persons who are APOE 4 positive. We propose to conduct a 24-week, randomized, double-blind, placebo-controlled, parallel group study of the Exelon® [rivastigmine] transdermal patch in 120 aMCI patients who have one or both APOE 4 alleles. Our preliminary analyses indicate that aMCI patients, even those who convert to AD, exhibit increased fMRI activation on our semantic memory activation task relative to not at-risk healthy participants and that increasing activation over time correlates with declines on neuropsychological testing. In addition, our preliminary data indicate that ChEI treated aMCI patients demonstrate normalization (i.e. reduction) in the magnitude of task-related neural activation over time relative to an untreated group. Furthermore, changes in fMRI magnitude demonstrated greater sensitivity to cholinergic modulation than changes on neuropsychological testing.

Official Title
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24-week, Randomized, Double-blind, Placebo-controlled, Parallel Group Study of the Exelon® [Rivastigmine] Transdermal Patch in 120 APOE e4 Positive Amnestic MCI Patients

Conditions
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Mild Cognitive Disorder, Mild Cognitive Impairment

Intervention / Treatment
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* Drug: Exelon [rivastigmine] transdermal patch
* Drug: Placebo transdermal patch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of amnestic MCI In good general health with no diseases expected to interfere with the study Ability to undergo MRI Fluent in English Stable prescription dosages 1 month prior to testing Carrier of the APOE e4 allele (determined by blood draw at screening visit) Exclusion Criteria: Neurological illness/conditions Medical illnesses/conditions that may affect brain function Prior history of use of any cholinesterase inhibitor Instable or severe cardiovascular disease or asthmatic condition

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Exelon transdermal patch<br>Exelon [rivastigmine] transdermal patch | Drug: Exelon [rivastigmine] transdermal patch<br>* Exelon patch 1/day for six months<br>* Other names: Rivastigmine;|
| Placebo Comparator: Placebo transdermal patch<br>Placebo transdermal patch | Drug: Placebo transdermal patch<br>* Placebo transdermal patch 1/day for 6 months<br>* Other names: Placebo patch;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BOLD Response on Functional Magnetic Resonance Imaging (fMRI) |  | baseline and 6 months |