Memantine and Intensive Speech-Language Therapy in Aphasia

Completed

Phase 4 Results N/A

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.

Conditions

Interventions

  • Memantine (Ebixa)Drug
    Intervention Desc: Memantine was titrated in 5-mg weekly increments as recommended, from a starting dose of 5 mg/day to 20 mg/day. After the 3-week up-titration 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). During the next 2 weeks (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 treatment alone and, finally, by a 4-week period of drug withdrawal (weeks 20-24).
    ARM 1: Kind: Experimental
    Label: Group 1 Memantine
    Description: Patients included in this group will receive memantine alone followed by memantine combined with intensive speech-language therapy.
  • Placebo Drug
    Intervention Desc: Placebo
    ARM 1: Kind: Experimental
    Label: Group 2
    Description: Patients included in this group will receive placebo alone followed by memantine combined with intensive speech-language therapy.
  • Constraint-induced language therapy (CIAT) Behavioral
    Other Names: Intensive language-action therapy
    Intervention Desc: CIAT is an intensive form of language-action therapy for aphasia performed in a small group setting. In a therapeutic game context, participants had to request objects or cards from each other and understand requests made by others. Feedback of communicative success was regularly given, along with guidance, help and reinforcement. Gesturing replacing verbal language was discouraged although gestures accompanying speech were allowed. Difficulty levels were adjusted to the patients´ communicative abilities by choosing language materials and actions and reinforcement was administered taking into account each patient´s level of performance. Communication rules were introduced by shaping and modelling. Each patient received 30 hours of therapy.
    ARM 1: Kind: Experimental
    Label: Group 1 Memantine
    Description: Patients included in this group will receive memantine alone followed by memantine combined with intensive speech-language therapy.
    ARM 2: Kind: Experimental
    Label: Group 2
    Description: Patients included in this group will receive placebo alone followed by memantine combined with intensive speech-language therapy.

Trial Design

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

Outcomes

Type Measure Time Frame Safety Issue
Primary Language function (overall aphasia severity). 24 weeks Yes
Secondary Depression 24 weeks No
Secondary Cognitive evaluation of language function 24 weeks No
Secondary Changes in event-related potential 24 weeks No

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