Enhancing Rehabilitation After Stroke (Enhance)

This study is currently recruiting participants.
Verified March 2013 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor:
Information provided by (Responsible Party):
Ellen Whyte, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00868010
First received: March 22, 2009
Last updated: March 4, 2013
Last verified: March 2013

March 22, 2009
March 4, 2013
March 2009
August 2013   (final data collection date for primary outcome measure)
Functional Independence Measure (FIM) [ Time Frame: Weekly/12 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00868010 on ClinicalTrials.gov Archive Site
Cognitive Function (ImPACT battery used to assess attention - working memory continuum, information processing speed, and verbal and visual episodic memory.) [ Time Frame: Multiple time points over 12 weeks ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Enhancing Rehabilitation After Stroke
Donepezil to Promote Functional Recovery Post-stroke

This is a 12-week, randomized, placebo controlled study to determine if donepezil (Aricept) treatment during rehabilitation after stroke improves functional recovery.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Ischemic Stroke
  • Drug: donepezil
    5 mg or 10 mg, titrated per drug insert. Participants may remain in the study at 5 mg if unable to tolerate 10 mg.
    Other Name: Aricept
  • Drug: placebo
    Participants will receive a placebo pill for 12 weeks if randomized to this treatment.
  • Experimental: 1: donepezil
    Participants will receive treatment for 12 weeks on donepezil 10 mg (or 5 mg if unable to tolerate 10 mg). Treatment will be then be terminated and participants followed for another 12 weeks naturalistically.
    Intervention: Drug: donepezil
  • Placebo Comparator: 2. placebo
    Participants will receive treatment for 12 weeks with placebo pill. Treatment will be then be terminated and participants followed for another 12 weeks naturalistically.
    Intervention: Drug: placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
200
November 2013
August 2013   (final data collection date for primary outcome measure)

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, exclusion criteria will include (a) ECG evidence of second or third degree heart block ( b ) ECG evidence of a tri-fascicular block (LBBB and 1st degree AV Block; RBBB, left anterior or left posterior hemiblock, and 1st degree AV block) or ( c ) history of syncope within 1 year with a RBBB or a LBBB.
  17. For females of child-bearing age, current pregnancy, plan to become pregnant while on study drug, or refusal to avoid pregnancy while on study drug.
  18. For females of child-bearing age, current breast feeding.
  19. suicidal attempt in the past one year,
  20. an inpatient admission for depression in the past one year
Both
18 Years and older
No
Contact: Kara Kenton 412-246-5815 kentonkd@upmc.edu
United States
 
NCT00868010
1 R01 HD055525, NIH grant: 1 R01 HD055525-01A2
Yes
Ellen Whyte, University of Pittsburgh
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Not Provided
Principal Investigator: Ellen M Whyte, MD University of Pittsburgh
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP