Enhancing Rehabilitation After Stroke

Ischemic Stroke Clinical Trial

— Enhance  

Official title:

Donepezil to Promote Functional Recovery Post-stroke

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00868010
• Other study ID #: 1R01HD055525
• Secondary ID: NIH grant: 1 R01
• Status: Recruiting
• Phase: Phase 3
• First received: March 22, 2009
• Last updated: March 4, 2013
• Start date: March 2009
• Est. completion date: November 2013

Study information

• Verified date: March 2013
• Source: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Contact: Kara Kenton
• Phone: 412-246-5815
• Email: kentonkd[@]upmc.edu
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: November 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ischemic Stroke
• Stroke

Intervention

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.
• placebo
Participants will receive a placebo pill for 12 weeks if randomized to this treatment.

Locations

Country	Name	City	State
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Hillside Rehabilitation Hospital	Warren	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Thom T, Haase N, Rosamond W, Howard VJ, Rumsfeld J, Manolio T, Zheng ZJ, Flegal K, O'Donnell C, Kittner S, Lloyd-Jones D, Goff DC Jr, Hong Y, Adams R, Friday G, Furie K, Gorelick P, Kissela B, Marler J, Meigs J, Roger V, Sidney S, Sorlie P, Steinberger J, Wasserthiel-Smoller S, Wilson M, Wolf P; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2006 Feb 14;113(6):e85-151. Epub 2006 Jan 11. Erratum in: Circulation. 2006 Apr 11;113(14):e696. Circulation. 2006 Dec 5;114(23):e630. — View Citation

Whyte EM, Lenze EJ, Butters M, Skidmore E, Koenig K, Dew MA, Penrod L, Mulsant BH, Pollock BG, Cabacungan L, Reynolds CF 3rd, Munin MC. An open-label pilot study of acetylcholinesterase inhibitors to promote functional recovery in elderly cognitively impaired stroke patients. Cerebrovasc Dis. 2008;26(3):317-21. doi: 10.1159/000149580. Epub 2008 Jul 31. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Functional Independence Measure (FIM)		Weekly/12 weeks	No
Secondary	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	No

External Links

•   American Stroke Association website provides general information regarding stroke and stroke prevention.