Donepezil Trial for Motor Recovery in Acute Stroke

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Acute Stroke
• Intervention / Treatment: Drug: Donepezil; Drug: Placebo

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.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital, Imperial College Academic Health Science Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.
Experimental: Donepezil	Drug: Donepezil; 5mg for 4 weeks, 10mg for 8 weeks if tolerated, or lower dose to continue; Other Names: Aricept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: International Stem Cell Forum
• Investigators: Principal Investigator: Paul Bentley, MA MRCP PhD, Imperial College London

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2011
• Primary Completion (Estimated): November 1, 2013
• Study Completion (Estimated): May 1, 2014

Study Registration Dates

• First Submitted: September 21, 2011
• First Submitted That Met QC Criteria: September 28, 2011
• First Posted (Estimated): September 29, 2011

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: stroke; motor; cholinesterase inhibitor; donepezil
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: CRO1793

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No