Effect of Acetylcholinesterase Inhibitors on the Gait of the Patients With Parkinson Disease

Study Overview
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Brief Summary
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Cholinergic deficiency in the brain can be related to gait and balance problems in Parkinson disease (PD). Recent clinical trials suggested a beneficial role of acetylcholinesterase inhibitors (AchEI) on gait in PD. In this study, the investigators are planning to study the influence of AchEI on a brain network for gait and balance in PD. As gait problem is prominent in postural instability and gait disturbance (PIGD) subtype, this study will focus on the patients with PIGD phenotype.

Detailed Description
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PD patients with PIGD subtype will be included. Assessment: Overall features of PD are assessed by Unified Parkinson Disease Rating Scale (UPDRS). Non-motor features including cognition will be assessed by standard scales. Gait and balance will be assessed by gait analysis system, which measures physiological parameters of gait such as velocity, variability and center of pressure. Positron emission tomography using 18F-fluorodeoxyglucose (FDG PET) will be done to brain activities related to gait and balance. Clinical evaluation will be done at the baseline, 4th, 8th and 12th week Gait analysis and FDG PET will be done at the baseline and 12th week Drug dosage For the first 4 weeks, 5 mg/day Then, 10 mg/day for 8 weeks

Official Title
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Effect of Acetylcholinesterase Inhibitors on the Gait of the Patients With Parkinson Disease Characterized by Postural Instability and Gait Disturbance

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Donepezil
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parkinson disease diagnosed by United Kingdom Parkinson's disease Society Brain Bank Criteria Postural instability and gait disturbance phenotype Hoehn and Yahr stage ≤ 3 Mini-Mental status examination ≥ 24 Exclusion Criteria: Significant motor complication affecting daily activities Drugs related to acetylcholine metabolism

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Donepezil<br>dosage: 5mg, 10mg frequency: once a day duration: 12 weeks | Drug: Donepezil<br>* Start with 5 mg/day for 4 weeks Increased to 10 mg/day for 8 weeks<br>* Other names: Aridone;|
| Placebo Comparator: Placebos<br>dosage: 5mg, 10mg frequency: once a day duration: 12 weeks | Drug: Placebos<br>* Start with 5 mg/day for 4 weeks Increased to 10 mg/day for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positron emission tomography using 18F-flurodeoxyglucose |  | Metabolic change from Baseline at 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montreal Cognitive Assessment |  | Baseline assessment/ Follow-up assessment at 12th week | 
| Unified Parkinson disease rating scale (UPDRS) |  | Baseline assessment/ Follow-up assessment at 4th, 8th and 12th week | 
| Time-Up and Go |  | Baseline assessment/ Follow-up assessment at 4th, 8th and 12th week | 
| Gait analysis | Composite measures of gait and balance | Baseline assessment/ Follow-up assessment at 4th, 8th and 12th week |