Donepezil Trial for Motor Recovery in Acute Stroke

Study Overview
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Brief Summary
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AIMS: To establish: 1) whether motor deficits in acute stroke improve more in patients taking donepezil, relative to placebo, for 12 weeks; 2) whether brain functional MRI changes as a result of donepezil after 12 weeks.

Detailed Description
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Stroke is a major personal and social burden, being the commonest cause of severe adult disability. Recovery has been shown in animal models to be dependent upon adequate levels of acetylcholine within the brain - which in stroke is likely to be deficient. This is because acetylcholine-producing nerve cells in the brain are often damaged by strokes. Consequently, the investigators hypothesise that recovery may be improved by boosting acetylcholine levels in the brain - that can be readily achieved by treating with donepezil.

Official Title
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A Randomised-controlled Trial of Donepezil for Motor Recovery in Acute Stroke

Conditions
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Acute Stroke

Intervention / Treatment
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* Drug: Donepezil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with acute stroke diagnosed on clinical and neuroimaging grounds who can enter the trial within the 1st week of stroke onset, and who have new motor dysfunction of an upper limb. Motor impairment should be moderate - severe (UE-FM Score ≤50 out of a total of 66). Age: above 18 years old. Patients able and willing to partake in motor tests, and to return for follow-up visit at 12 weeks. Able to understand English. Exclusion Criteria: Contraindications for donepezil: pregnancy (* Female patients <50 years old will be asked if there is any possibility that they might be pregnant. If there is any uncertainty, or a likelihood that they are pregnant, this will qualify as an exclusion criterion)*; moderate - severe asthma (i.e. regular treatment prescribed for this); bradycardia, syncope, 2nd or 3rd degree heart block, acute or decompensated heart failure; peptic ulcer diagnosed endoscopically and on treatment for this; epilepsy; Parkinson's disease; end-stage renal failure or creatinine > 300 micromol/l; genitourinary tract or gastrointestinal tract obstruction; gastrointestinal tract hemorrhage; myasthenia gravis Other: functionally-significant cognitive impairment (i.e. dementia); significant receptive aphasia (i.e. such that cannot understand purpose or details of trial, and will be unable to cooperate with task instructions); significant physical infirmity as judged by treating physician (e.g. severe organ failure; terminal cancer). Contraindications for MRI (this only pertains for the subset of patients entering the MRI substudy, but is not a contra-indication to the main study providing a diagnosis of stroke is clear from CT): phobia, metal implants including pacemaker.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Experimental: Donepezil<br> | Drug: Donepezil<br>* 5mg for 4 weeks, 10mg for 8 weeks if tolerated, or lower dose to continue<br>* Other names: Aricept;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Inert pill that appears identical to donepezil pill. 1 pill for first 4 weeks, followed by 2 pills until end of study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Upper Extremity Fugl-Meyer Motor Score (out of 66) over 12 weeks |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Functional MRI Connectivity and Task-related activation (relative % BOLD signal change) over 12 weeks | resting-state / activation-related fMRI | 12 weeks | 
| Number and type of participants with adverse events | Self-reported / Questionnaire | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cholinesterase inhibitor, donepezil, motor, stroke