Enhancing Rehabilitation After Stroke (Enhance)

This study is currently recruiting participants. (see Contacts and Locations)
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
  Purpose

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


Condition Intervention Phase
Ischemic Stroke
Drug: donepezil
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Donepezil to Promote Functional Recovery Post-stroke

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Functional Independence Measure (FIM) [ Time Frame: Weekly/12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 200
Study Start Date: March 2009
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
Drug: placebo
Participants will receive a placebo pill for 12 weeks if randomized to this treatment.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00868010

Contacts
Contact: Kara Kenton 412-246-5815 kentonkd@upmc.edu

Locations
United States, Ohio
Hillside Rehabilitation Hospital Not yet recruiting
Warren, Ohio, United States, 44484
Contact: Nancy Landgraff, PhD    330-941-2703    nlandgra@cc.ysu.edu   
Principal Investigator: Nancy Landgraff, PhD         
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Kara Kenton    412-246-5815    kentonkd@upmc.edu   
Sub-Investigator: Howard Aizenstein, MD, PhD         
Principal Investigator: Ellen M Whyte, MD         
Sub-Investigator: Meryl Butters, PhD         
Sub-Investigator: Ariel Gildengers, MD         
Sub-Investigator: Jordan Karp, MD         
Sub-Investigator: Oscar Lopez, MD         
Sub-Investigator: Sati Mazumdar, MD         
Sub-Investigator: Michael Munin, MD         
Sub-Investigator: Charles Reynolds, MD         
Sub-Investigator: Elizabeth Skidmore, PhD         
Sponsors and Collaborators
Investigators
Principal Investigator: Ellen M Whyte, MD University of Pittsburgh
  More Information

Additional Information:
Publications:
Responsible Party: Ellen Whyte, Principal Investigator, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00868010     History of Changes
Other Study ID Numbers: 1 R01 HD055525, NIH grant: 1 R01 HD055525-01A2
Study First Received: March 22, 2009
Last Updated: March 4, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
stroke
donepezil
recovery

Additional relevant MeSH terms:
Stroke
Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Donepezil
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 31, 2014