Study of Exelon Transdermal Patch in Amnestic Mild Cognitive Impairment Patients

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

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

Study Overview

• Status: Terminated
• Conditions: Mild Cognitive Impairment; Mild Cognitive Disorder
• Intervention / Treatment: Drug: Exelon [rivastigmine] transdermal patch; Drug: Placebo transdermal patch

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 51 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Exelon transdermal patch; Exelon [rivastigmine] transdermal patch	Drug: Exelon [rivastigmine] transdermal patch; Exelon patch 1/day for six months; Other Names: Rivastigmine
Placebo Comparator: Placebo transdermal patch	Drug: Placebo transdermal patch; Placebo transdermal patch 1/day for 6 months; Other Names: Placebo patch

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Stephen M Rao, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: June 13, 2011
• First Submitted That Met QC Criteria: May 16, 2012
• First Posted (Estimate): May 18, 2012

Study Record Updates

• Last Update Posted (Actual): February 28, 2017
• Last Update Submitted That Met QC Criteria: January 9, 2017
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognitive Dysfunction; Cognition Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Cholinesterase Inhibitors; Rivastigmine
• Other Study ID Numbers: AG022304

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No data to share.