Memantine and Constraint-Induced Language Therapy in Chronic Poststroke Aphasia:A Randomized Controlled Trial


Phase 4 Results

Trial Description

- Aphasia, the loss or impairment of language caused by brain damage, is one of the most devastating cognitive impairments of stroke. Aphasia can be treated with combination of speech-language therapy and drugs. Conventional speech-language therapy in chronic aphasic subjects is of little help and several drugs have been studied with limited success. Therefore other therapeutic strategies are warranted.
- Recent data suggest that drugs (memantine) acting on the brain chemical glutamate may help the recovery of cognitive deficits, included language, in subjects with vascular dementia. The present study examines the safety profile and efficacy of memantine paired with intensive language therapy in subjects with stroke-related chronic aphasia (more than 1 yr. of evolution).

Detailed Description

- The efficacy of drugs that act on glutamate such as the N-methyl-D-aspartic acid (NMDA) receptor antagonist memantine requires to be explored in this population. The rationale for using memantine in post-stroke aphasia comes from recent studies on vascular dementia. Data extracted from a recent Cochrane review of randomized controlled trials of memantine in different types of dementia (vascular dementia, Alzheimer's disease, mixed dementia) reveal, after 6 weeks of treatment, beneficial effects on cognition (including language), activities of daily living, behavior and global scales as well as in the global impression of change.
- Recovery from aphasia is possible even in severe cases. While speech-language therapy remains as the mainstay treatment of aphasia, its effectiveness has not been conclusively proved. This has motivated the planning of more rational therapies (e.g., constraint-induced language therapy [Pulvermüller et al., 2001; 32: 1621-1626]).
- In addition, the neural correlates of improvement of language function can now be readily detectable with event-related potentials. This is a noninvasive technique that can detect in real time functional brain changes during recovery promoted by the combined action of memantine and constraint-induced language therapy.
- The aim of the present study is to assess the efficacy, safety profile, and functional correlates of memantine paired with massed language therapy in a sample of patients with chronic poststroke aphasia.



Trial Design

  • Allocation: Randomized
  • Masking: Double-Blind
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

Patients underwent a 3-week up-titration phase of either memantine or placebo. Memantine was titrated in 5 mg weekly from a starting dose of 5 mg/day to 20 mg/day. After the dose-escalation phase all patients received a fixed dose of either memantine (10 mg) or placebo twice daily without CIAT during the next 3 months (week 16). Then, during weeks 16-18, the drug treatment was combined with CIAT. This phase of combined treatment was followed by a 2-week period (weeks 18-20) where patients received memantine or placebo treament alone and, finally, by a 4-week period of drug washout (weeks 20-24). Evaluation of aphasia (Western Aphasia Battery - WAB) and communication(Communicative Activity Log - CAL) were performed at baseline and at the end of weeks 16 and 18 (endpoints) and of weeks 20 and 24 (washout).Patients who completed the double-blind phase participated in the open-label extension. Baseline evaluation for the open-label phase coincided with the double-blind study termination visit (week 24). Thus, 4 weeks after stopping memantine or placebo, all patients, including those whohad received memantine during the double-blind phase, switched directly to memantine for 24 weeks. No patient received CIAT during this period.


Type Measure Time Frame Safety Issue
Secondary Depression; Cognitive evaluation of language function; Changes in event-related potential.
Primary Language function (overall aphasia severity).
Primary Communication
Secondary Depression
Secondary Cognitive evaluation of language function
Secondary Changes in event-related potential