Donepezil Trial for Motor Recovery in Acute Stroke
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Purpose
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.
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Acute Stroke |
Drug: Donepezil Drug: Placebo |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Randomised-controlled Trial of Donepezil for Motor Recovery in Acute Stroke |
- Change in Upper Extremity Fugl-Meyer Motor Score (out of 66) over 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Change in Functional MRI Connectivity and Task-related activation (relative % BOLD signal change) over 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]resting-state / activation-related fMRI
- Number and type of participants with adverse events [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]Self-reported / Questionnaire
| Estimated Enrollment: | 100 |
| Study Start Date: | November 2011 |
| Estimated Study Completion Date: | May 2014 |
| Estimated Primary Completion Date: | November 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Donepezil |
Drug: Donepezil
5mg for 4 weeks, 10mg for 8 weeks if tolerated, or lower dose to continue
Other Name: Aricept
|
| Placebo Comparator: Placebo |
Drug: Placebo
Inert pill that appears identical to donepezil pill. 1 pill for first 4 weeks, followed by 2 pills until end of study.
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations| Contact: Paul Bentley, MA MRCP PhD | 02033111184 | p.bentley@imperial.ac.uk |
| United Kingdom | |
| Charing Cross Hospital, Imperial College Academic Health Science Centre | Not yet recruiting |
| London, United Kingdom, W6 8RF | |
| Contact: Paul Bentley, MA MRCP PhD 02033111184 p.bentley@imperial.ac.uk | |
| Principal Investigator: | Paul Bentley, MA MRCP PhD | Imperial College London |
More Information
No publications provided
| Responsible Party: | Imperial College London |
| ClinicalTrials.gov Identifier: | NCT01442766 History of Changes |
| Other Study ID Numbers: | CRO1793 |
| Study First Received: | September 21, 2011 |
| Last Updated: | September 29, 2011 |
| Health Authority: | United Kingdom: Medicines and Healthcare Products Regulatory Agency |
Keywords provided by Imperial College London:
|
cholinesterase inhibitor donepezil motor stroke |
Additional relevant MeSH terms:
|
Stroke Cerebral Infarction Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Vascular Diseases Cardiovascular Diseases Brain Infarction Brain Ischemia Cholinesterase Inhibitors |
Donepezil Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Cholinergic Agents Neurotransmitter Agents Physiological Effects of Drugs Nootropic Agents Central Nervous System Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 16, 2013