Donepezil in Chronic Poststroke Aphasia: a Randomized Controlled Trial

NCT ID: NCT00196690

Last Updated: 2005-09-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-02-28
• Study Completion Date: 2005-03-31

Brief 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).

Detailed 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.

Conditions

Stroke; Aphasia

Keywords

Aphasia; Donepezil

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

Donepezil

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Gabinete Berthier y Martínez

OTHER

Sponsor Role: lead

Principal Investigators

Marcelo L. Berthier, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Gabinete Berthier y Martínez. Malaga, Spain. Centro de Investigaciones Médico-Sanitarias (CIMES), University of Malaga, Malaga, Spain

Locations

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

Málaga, Malaga, Spain

Countries

Spain

References

Berthier ML. Poststroke aphasia : epidemiology, pathophysiology and treatment. Drugs Aging. 2005;22(2):163-82. doi: 10.2165/00002512-200522020-00006.

Reference Type: BACKGROUND

PMID: 15733022 (View on PubMed)

Other Identifiers

02-0509

Identifier Type: -

Identifier Source: org_study_id