Donepezil Trial for Motor Recovery in Acute Stroke
Primary Purpose
Acute Stroke
Status
Terminated
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Donepezil
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Acute Stroke focused on measuring cholinesterase inhibitor, donepezil, motor, stroke
Eligibility Criteria
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.
Sites / Locations
- Charing Cross Hospital, Imperial College Academic Health Science Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Donepezil
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Change in Upper Extremity Fugl-Meyer Motor Score (out of 66) over 12 weeks
Secondary Outcome Measures
Change in Functional MRI Connectivity and Task-related activation (relative % BOLD signal change) over 12 weeks
resting-state / activation-related fMRI
Number and type of participants with adverse events
Self-reported / Questionnaire
Full Information
NCT ID
NCT01442766
First Posted
September 21, 2011
Last Updated
September 23, 2019
Sponsor
Imperial College London
Collaborators
International Stem Cell Forum
1. Study Identification
Unique Protocol Identification Number
NCT01442766
Brief Title
Donepezil Trial for Motor Recovery in Acute Stroke
Official Title
A Randomised-controlled Trial of Donepezil for Motor Recovery in Acute Stroke
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Terminated
Why Stopped
No financial support
Study Start Date
November 2011 (Actual)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
May 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College London
Collaborators
International Stem Cell Forum
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Stroke
Keywords
cholinesterase inhibitor, donepezil, motor, stroke
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Donepezil
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Donepezil
Other Intervention Name(s)
Aricept
Intervention Description
5mg for 4 weeks, 10mg for 8 weeks if tolerated, or lower dose to continue
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Inert pill that appears identical to donepezil pill. 1 pill for first 4 weeks, followed by 2 pills until end of study.
Primary Outcome Measure Information:
Title
Change in Upper Extremity Fugl-Meyer Motor Score (out of 66) over 12 weeks
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Change in Functional MRI Connectivity and Task-related activation (relative % BOLD signal change) over 12 weeks
Description
resting-state / activation-related fMRI
Time Frame
12 weeks
Title
Number and type of participants with adverse events
Description
Self-reported / Questionnaire
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Bentley, MA MRCP PhD
Organizational Affiliation
Imperial College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charing Cross Hospital, Imperial College Academic Health Science Centre
City
London
ZIP/Postal Code
W6 8RF
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
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Donepezil Trial for Motor Recovery in Acute Stroke
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