Mild Cognitive Disorder, Mild Cognitive Impairment
Conditions
Brief summary
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
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.
Interventions
DRUGExelon [rivastigmine] transdermal patch
Exelon patch 1/day for six months
Placebo transdermal patch 1/day for 6 months
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in BOLD Response on Functional Magnetic Resonance Imaging (fMRI) | baseline and 6 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Exelon Transdermal Patch Exelon \[rivastigmine\] transdermal patch
Exelon \[rivastigmine\] transdermal patch: Exelon patch 1/day for six months | 0 |
| Placebo Transdermal Patch Placebo transdermal patch
Placebo patch: Placebo patch 1/day for 6 months | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Exelon Transdermal Patch | Placebo Transdermal Patch | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gender Female | 0 Participants | 1 Participants | 1 Participants |
| Gender Male | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | — | 1 participants | 1 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 1 / 1 |
| serious Total, serious adverse events | 0 / 0 | 0 / 1 |
Outcome results
Primary
Change in BOLD Response on Functional Magnetic Resonance Imaging (fMRI)
Time frame: baseline and 6 months
Population: Trial was terminated prematurely after enrollment of only 1 participant. Sample size is insufficient for BOLD response analysis.