Donepezil in Chronic Poststroke Aphasia: a Randomized Controlled Trial

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by:
Gabinete Berthier y Martínez
ClinicalTrials.gov Identifier:
NCT00196690
First received: September 12, 2005
Last updated: NA
Last verified: September 2005
History: No changes posted
  Purpose
  • 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).

Condition Intervention Phase
Stroke
Aphasia
Drug: Donepezil
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Treatment With Donepezil of Chronic Aphasia and Sensorimotor Deficits Associated to Cerebrovascular Accidents: a Double-Blind,Placebo-Controlled, Randomized Parallel Trial.

Resource links provided by NLM:


Further study details as provided by Gabinete Berthier y Martínez:

Primary Outcome Measures:
  • Language function (overall aphasia severity)
  • Communication

Secondary Outcome Measures:
  • Depression
  • Cognitive evaluation of language function

Estimated Enrollment: 30
Study Start Date: February 2003
Estimated Study Completion Date: March 2005
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.
  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00196690

Locations
Spain
Gabinete Berthier y Martínez, Malaga, Spain. Centro de Investigaciones Médico-Sanitarias (CIMES), UNiversity of Malaga, Malaga, Spain.
Malaga, Spain, 29001
Sponsors and Collaborators
Gabinete Berthier y Martínez
Pfizer
Investigators
Principal Investigator: Marcelo L. Berthier, M.D., Ph.D. Gabinete Berthier y Martínez. Malaga, Spain. Centro de Investigaciones Médico-Sanitarias (CIMES), University of Malaga, Malaga, Spain
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00196690     History of Changes
Other Study ID Numbers: 02-0509
Study First Received: September 12, 2005
Last Updated: September 12, 2005
Health Authority: Spain: Ministry of Health and Consumption

Keywords provided by Gabinete Berthier y Martínez:
Aphasia
Donepezil

Additional relevant MeSH terms:
Aphasia
Stroke
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
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 22, 2014