Memantine and Intensive Speech-Language Therapy in Aphasia

Stroke Clinical Trial

Official title:

A 24-Week Pilot, Double-Blind, Randomized, Parallel, Placebo-Controlled Study of Memantine and Constraint-Induced Language Therapy in Chronic Poststroke Aphasia:Correlation With Cognitive Evoked Potentials During Recovery.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00640198
• Other study ID #: M-10830
• Secondary ID: Gabinete Berthie
• Status: Completed
• Phase: Phase 4
• First received: March 17, 2008
• Last updated: March 20, 2008
• Start date: March 2005
• Est. completion date: November 2007

Study information

• Verified date: March 2008
• 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, 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: November 2007
• Est. primary completion date: November 2007
• 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:

• Dementia

• Major psychiatric illness

• Severe global aphasia (precludes participation in constraint-induced language therapy)

Study Design

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

Related Conditions & MeSH terms

• Aphasia
• Stroke

Intervention

Drug:
• memantine
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)

Behavioral:
• constraint-induced language therapy (CIAT)
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.

Drug:
• memantine
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).
• placebo
Placebo

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Gabinete Berthier y Martínez	H. Lundbeck A/S

Country where clinical trial is conducted

Spain, 

References & Publications (3)

Orgogozo JM, Rigaud AS, Stöffler A, Möbius HJ, Forette F. Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM 300). Stroke. 2002 Jul;33(7):1834-9. — View Citation

Pantoni L. Treatment of vascular dementia: evidence from trials with non-cholinergic drugs. J Neurol Sci. 2004 Nov 15;226(1-2):67-70. Review. — View Citation

Romàn G. Perspectives in the treatment of vascular dementia. Drugs Today (Barc). 2000 Sep;36(9):641-53. — View Citation

Outcome

Type	Measure	Description	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