Enhancing Rehabilitation After Stroke "Enhance"

Recruiting

Phase 3 Results N/A

Trial Description

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.

Conditions

Interventions

  • Donepezil hydrochloride (Aricept ®)Behavioral
    Intervention Desc: Reversible inhibitor of acetylcholinesterase.
  • Placebo Drug
    Intervention Desc: Participants will receive a placebo pill for 12 weeks if randomized to this treatment.
    ARM 1: Kind: Experimental
    Label: 2. placebo
    Description: Participants will receive treatment for 12 weeks with placebo pill. Treatment will be then be terminated and participants followed for another 12 weeks naturalistically.
  • Donepezil Drug
    Other Names: Aricept
    Intervention Desc: 5 mg or 10 mg, titrated per drug insert. Participants may remain in the study at 5 mg if unable to tolerate 10 mg.
    ARM 1: Kind: Experimental
    Label: 1: donepezil
    Description: 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.

Trial Design

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

Patient Involvement

Participants will be randomized to one of two arms. In arm 1: 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. Participants in arm 2. will receive treatment for 12 weeks with placebo pill. Treatment will be then be terminated and participants followed for another 12 weeks naturalistically.

Outcomes

Type Measure Time Frame Safety Issue
Primary Functional Independence Measure (FIM)
Secondary Cognitive Function (ImPACT battery used to assess attention - working memory continuum, information processing speed, and verbal and visual episodic memory.)

Sponsors