Clinical trial NCT01442766: 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
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Acute Stroke
Keywords: cholinesterase inhibitor
donepezil
motor
stroke
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: International Stem Cell Forum
First posted: 2011-09-29
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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).
2. Age: above 18 years old.
3. Patients able and willing to partake in motor tests, and to return for follow-up visit at 12 weeks.
4. Able to understand English.

Exclusion Criteria:

1. 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
2. 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).
3. 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.

Primary outcomes:
measure: Change in Upper Extremity Fugl-Meyer Motor Score (out of 66) over 12 weeks
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in Functional MRI Connectivity and Task-related activation (relative % BOLD signal change) over 12 weeks
timeFrame: 12 weeks
measure: Number and type of participants with adverse events
timeFrame: 12 weeks
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Charing Cross Hospital, Imperial College Academic Health Science Centre
Study officials:
affiliation: Imperial College London
name: Paul Bentley, MA MRCP PhD
role: PRINCIPAL_INVESTIGATOR
References: