The Effect of Donepezil on Gait and Balance in Parkinson's Disease

Study Overview
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Brief Summary
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This study involves Parkinson's disease (PD). Symptoms include slow movement, tremor, and muscle rigidity. Current medications for the treatment of PD do not improve gait and balance difficulties in individuals with PD. Donepezil (study drug) has been found to reduce falls in individuals with PD. The mechanism in which this reduction of falls occurs is unclear. The investigators study will look at what aspects of gait and balance are improved by the study drug. The study drug is not approved to treat PD in the United States or other countries because we do not know enough about it.

Detailed Description
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Parkinson's disease (PD) is a common neuro-degenerative disease affecting about 2% of the adult population in the United States over the age of 65. Some of the most disabling symptoms of Parkinson's disease are balance and gait dysfunction, leading to falls. These symptoms do not respond to current dopamine directed therapies. Evidence from both pathologic studies and advanced imaging has demonstrated that a cholinergic deficiency in the thalamus and basal ganglia is found in individuals with PD who fall compared to non-fallers. The central acting acetylcholine esterase inhibitor, donepezil, has been demonstrated to decrease falls in individuals with PD. The mechanism by which falls decreased is unknown. Our open label pilot data indicates that donepezil can improve quantitative measures of balance in individuals with PD. Suggesting that improvements in balance in the mechanism by which donepezil reduces falls. Our goal is to determine whether donepezil will: Improve quantitative measures of balance in subjects with Parkinson's disease compared to placebo. Improve quantitative measures of gait in subjects with Parkinson's disease compared to placebo. Improve cognitive measures in non-demented subjects with Parkinson's disease.

Official Title
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A Randomized, Double-blind, Placebo Controlled, Crossover Study to Evaluate the Effect of Donepezil on Gait and Balance in Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Donepezil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Idiopathic Parkinson's disease, defined by the UK Brain Bank criteria, with a Hoehn and Yahr score of 2 to 4 Treated with levodopa for at least a year and on a stable antiparkinsonian regimen for at least one month Abnormal computerized dynamic posturography (CDP) on screening defined as a composite score below 65 (range 1-100) Exclusion Criteria: Dementia defined by MMSE less than 27 Other medical conditions other than PD affecting balance or gait as determined by the investigators Unable to stand unassisted for 30 minutes Current use of an acetylcholinesterase inhibitors or drugs with known anticholinergic properties Medical or psychiatric co-morbidities that may interfere with compliance or might place subject in danger as determined by the investigators
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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donepezil, Then Placebo<br>Donepezil 5 mg a day for weeks 1 - 3, if tolerated increased to 10 mg a day for weeks 4 - 6. After a washout period of 4 weeks, placebo 5 mg a day for weeks 1 - 3, if tolerated increased to 10 mg a day for weeks 4 - 6. | Drug: Donepezil<br>* Use 1 capsule (5 mg) of donepezil once per day for first 21 days than donepezil 10mg qday for 21 days.<br>* Other names: Aricept;Drug: Placebo<br>* Use 1 capsule (5 mg) once per day for first 21 days than 10mg qday for 21 days.<br>* Other names: Sugar Pill;|
| Experimental: Placebo, Then Donepezil<br>Placebo 5 mg a day for weeks 1 - 3, if tolerated increased to 10 mg a day for weeks 4 - 6. After a washout period of 4 weeks, donepezil 5 mg a day for weeks 1 - 3, if tolerated increased to 10 mg a day for weeks 4 - 6. | Drug: Donepezil<br>* Use 1 capsule (5 mg) of donepezil once per day for first 21 days than donepezil 10mg qday for 21 days.<br>* Other names: Aricept;Drug: Placebo<br>* Use 1 capsule (5 mg) once per day for first 21 days than 10mg qday for 21 days.<br>* Other names: Sugar Pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensory Organization Test - Composite Score | Balance was measured using the Sensory Organization test (SOT) on the NeuroCom Balance Master Clinical Research System platform (Neurocom International, Inc), which tests sway in 6 conditions, eyes open, eyes closed, and a moving visual surround first with a stable platform then with a moving platform. Center of Pressure (CoP) was calculated from the recordings. Forces and moments were recorded at 100Hz sampling frequency. A change score from the beginning of each treatment phase (placebo or active drug) to the end of the treatment phase. The SOT is scored on an interval scale with the highest possible score of 100 indicating no sway at all. The lowest possible score of 0 indicates the trial was stopped due to an impending fall. Higher scores are indicative of better balance (greater stability). | Change from Day 1 of each treatment phase to Day 42 of each treatment phase | 
| Sensory Organization Test (SOT) - Condition 4 (Eyes Open, Moving Surround, Stable Platform). | Condition 4 of the Sensory Organization Test. The participants eyes are open as the surround moves and the platform remains stable. A change score from the beginning of each treatment phase (placebo or active drug) to the end of the treatment phase. The SOT is scored on an interval scale with the highest possible score of 100 indicating no sway at all. The lowest possible score of 0 indicates the trial was stopped due to an impending fall. Higher scores are indicative of better balance (greater stability). | Change from Day 1 of each treatment phase to Day 42 of each treatment phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trails B - A | The Trail Making Test (TMT) consists of two parts (A & B) in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. The test provides information about visual search speed, scanning, speed of processing, and executive functioning. Part A measures processing speed and part B measures executive functioning. The TMT is time to complete each part of the test in seconds. Higher scores indicate greater impairment. Subtracting part A from part B (Trails B-A) is theorized to reduce the influence of the working memory and visuo-spatial demands and, therefore, provides a relatively pure indicator of executive function. A change score from the beginning of each treatment phase (placebo or active drug) to the end of the treatment phase. | Change from Day 1 of each treatment phase to Day 42 of each treatment phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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donepezil, parkinson's disease, balance, cholinesterase inhibitor