Ischemic Stroke
Conditions
Keywords
stroke, donepezil, recovery
Brief summary
This is a 12-week, randomized, placebo controlled study to determine if donepezil (Aricept) treatment during rehabilitation after stroke improves functional recovery.
Detailed description
Stroke is a leading cause of disability in the US (Thom 2006). The total number of stroke survivors (currently estimated as 5.5 million Americans) will continue to increase as the population ages and as the medical management of acute stroke continues to improve. Given stroke's devastating impact on activities of daily living and the large numbers of Americans afflicted, improving acute medical rehabilitation outcomes after stroke is of great public health importance. Predictors of poor functional recovery post-stroke include impairments in cognition and motivation. Recent evidence indicates that acetylcholinesterase inhibitors may improve cognition and motivation; hence, their use post-stroke may lead to improved rehabilitation outcomes. Our group has demonstrated that use of the acetylcholinesterase inhibitor donepezil is associated with improved functional recovery in a pilot sample (n = 40) of elderly, cognitively impaired stroke survivors undergoing inpatient rehabilitation. Specifically, in this 12 week open-label study, those subjects receiving donepezil experienced a clinically meaningful 14 point greater improvement on the Functional Independence Measure (FIM) than an archival comparator group. Based on these promising pilot study results, we propose a 12-week randomized, double-blind, placebo-controlled trial (followed by a 12 week off-drug observation period) in order to test the efficacy of donepezil to promote post-stroke functional recovery in older, cognitively impaired stroke survivors undergoing inpatient rehabilitation. We will also use this randomized controlled trial to examine the drug's effect on cognition post-stroke; specifically, the drug's effect on those cognitive domains (attention/working memory, information psychomotor speed, and episodic memory) that are relevant to functional outcomes.
Interventions
DRUGdonepezil
5 mg or 10 mg, titrated per drug insert. Participants may remain in the study at 5 mg if unable to tolerate 10 mg.
DRUGplacebo
Participants will receive a placebo pill for 12 weeks if randomized to this treatment.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. male or female; 2. aged 18 or older; 3. new ischemic stroke within the preceding 30 days; and 4. admitted to the an inpatient facility of the UPMC Institute for Rehabilitation and Research for post-stroke rehabilitation.
Exclusion criteria
1. primary hemorrhagic stroke; 2. current use of a cholinomimetic drug including tacrine, donepezil, galantamine, and rivastigmine; 3. contraindication to AchEi therapy including bradycardia (\< 50 bpm), severe asthma or COPD requiring nebulized medication, and active upper GI bleed or untreated gastric ulcer; 4. myocardial infarction, poorly controlled congestive heart failure, or coronary bypass surgery within the last 3 months; 5. current required use of an anticholinergic medication (e.g., for bladder spasm); 6. current aphasia severe enough to prevent valid neuropsychiatric assessment (e.g., a score \< 9 on the Token Test, part I and a score of \< 14 (or \<80% accuracy) on the repetition task of the Boston Diagnostic Aphasia Examination); 7. current Major Depressive Episode AND HRSD \> 20; 8. current active suicidal ideation, plan, or intent; 9. current mania or hypomania; 10. current psychosis; 11. meeting DMS-IV TR alcohol or substance abuse or dependence criteria within the preceding 3 months; 12. subject and/or family informant do not speak English; 13. history of a progressive or unstable CNS disease (e.g., multiple sclerosis, Parkinson's disease, HIV with CNS involvement); 14. medically unstable (determined by review of the subject's medical status with the treating (clinical) physician and by review of standard blood tests); and 15. history of sensitivity to donepezil; 16. for potential subjects without a pacemaker or implantable defibrillator,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Functional Independence Measure (FIM) | Weekly/12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Cognitive Function (ImPACT battery used to assess attention - working memory continuum, information processing speed, and verbal and visual episodic memory.) | Multiple time points over 12 weeks |
Countries
United States
Contacts
Primary ContactKara Kenton
Outcome results
None listed