Donepezil in Chronic Poststroke Aphasia: a Randomized Controlled Trial

Stroke Clinical Trial

Official title:

Treatment With Donepezil of Chronic Aphasia and Sensorimotor Deficits Associated to Cerebrovascular Accidents: a Double-Blind,Placebo-Controlled, Randomized Parallel Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00196690
• Other study ID #: 02-0509
• Status: Completed
• Phase: Phase 4
• First received: September 12, 2005
• Last updated: September 12, 2005
• Start date: February 2003
• Est. completion date: March 2005

Study information

• Verified date: September 2005
• Source: Gabinete Berthier y Martínez
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health and Consumption
• Study type: Interventional

Clinical Trial Summary

• Aphasia (impairment of language function due to brain damage)may be treated with speech-language therapy and drugs. Several drugs have been studied but with limited success.

• Recent data suggest that the neurotransmitter acetylcholine may be reduced in brain damaged subjects and that drugs that stimulates acetylcholine activity may help recovery of aphasic deficits particularly when paired with speech-language therapy.

• Recent evidence indicates that medicaments acting on the neurotransmitter acetylcholine may promote improvement of aphasic deficits and our previous open-label study of donepezil in post-stroke aphasia showed benefits in all patients and observed benefit were long-lasting (6 months).This study will test the safety and efficacy of donepezil (an agent acting on acetylcholine)in subjects with stroke-related chronic aphasia (more than 1 yr of evolution).

Description:

• Prior clinical information of donepezil treatment of post-stroke aphasia comes from single-case studies, small case-series and an open-label study. In addition, an extension phase of a small open-label study also suggest that the efficacy of donepezil in chronic post-stroke apahsia is maintained at long-term follow-up. These data collectively suggest that in post-stroke donepezil is effective and well-tolerated with a limited potential for causing clinically significant interactions when prescribed with other medications. However, these results are preliminary and should be judged parsimoniously until randomized controlled trials will be performed.Moreover, recent data by our group also showed that donepezil may improve sensorimotor deficits (hemiparesis)in some patients.

• The use of acetylcholinesterase inhibitors such as donepezil in post-stroke may be justified because in vivo and postmortem studies have shown that patients with vascular dementia and lesions in subcortical and cortical structures have deficient cholinergic neurotransmission that results from interruption of cholinergic pathways linking the basal forebrain with the cerebral cortex, including the perisylvian language area.In addition, two large-scale randomized controlled trials in patients pure vascular dementia and vascular cognitive impairment found that donepezil was significantly superior to placebo on cognition, global function and activities of daily living.And the most noticeable benefits of donepezil over placebo at doses of 5-mg and 10-mg were found on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog/11), an assessment instrument highly reliant upon language variables (6 out of 11 items).

• We evaluated the efficacy of donepezil in patients with chronic aphasia associated with stroke.This is a 20-week, randomized, placebo-controlled, double-blind parallel study that enrolled aphasic patient with more than one year of evolution. During the study all patients continued receiving two hours weekly of conventional speech-language therapy. Patients were randomized in an 1:1 ratio to donepezil, 5-mg/day, for the first 4 weeks, followed by forced dose escalation to 10-mg/day thereafter (n =13), or placebo (n = 13) and then a 4 week washout period. The primary efficacy measures were the Aphasia Quotient (AQ) of the Western Aphasia Battery and the Communicative Activity Log. Secondary efficacy measures included selected subtests of the Psycholinguistic Assessment of Language Processing in Aphasia that examined phonological and lexical-semantic domains and the Stroke Aphasia Depression Questionnaire.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: March 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 69 Years

Eligibility

Inclusion Criteria:

• Chronic aphasia of more than one year duration. Must be able to complete protocol.

Exclusion Criteria:

• Heart block

• Bronchial Asthma

• Hypersensitivity to donepezil

• Dementia

• Major psychiatric illness

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aphasia
• Stroke

Intervention

Drug:
• Donepezil

Locations

Country	Name	City	State
Spain	Gabinete Berthier y Martínez, Malaga, Spain. Centro de Investigaciones Médico-Sanitarias (CIMES), UNiversity of Malaga, Malaga, Spain.	Malaga

Sponsors (2)

Lead Sponsor	Collaborator
Gabinete Berthier y Martínez	Pfizer

Country where clinical trial is conducted

Spain, 

References & Publications (1)

Berthier ML. Poststroke aphasia : epidemiology, pathophysiology and treatment. Drugs Aging. 2005;22(2):163-82. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Language function (overall aphasia severity)
Primary	Communication
Secondary	Depression
Secondary	Cognitive evaluation of language function