Memantine and Intensive Speech-Language Therapy in Aphasia

NCT ID: NCT00640198

Last Updated: 2008-03-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-31
• Study Completion Date: 2007-11-30

Brief 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).

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

Aphasia; Stroke

Keywords

Aphasia; Memantine; Constraint-induced language therapy; Event-related potentials

Study Design

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

Study Groups

Group 1 Memantine

Patients included in this group will receive memantine alone followed by memantine combined with intensive speech-language therapy.

Group Type: ACTIVE_COMPARATOR

memantine

Intervention Type: DRUG

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)

constraint-induced language therapy (CIAT)

Intervention Type: BEHAVIORAL

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.

memantine

Intervention Type: DRUG

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).

Group 2

Patients included in this group will receive placebo alone followed by memantine combined with intensive speech-language therapy.

Group Type: PLACEBO_COMPARATOR

constraint-induced language therapy (CIAT)

Intervention Type: BEHAVIORAL

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.

placebo

Intervention Type: DRUG

Placebo

Interventions

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)

Intervention Type: DRUG

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.

Intervention Type: BEHAVIORAL

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).

Intervention Type: DRUG

placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

Ebixa, Namenda; Intensive language-action therapy; Ebixa, Namenda

Eligibility Criteria

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)

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

Sponsors

H. Lundbeck A/S

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 and Centro de Investigaciones Médico-Sanitarias (CIMES), University of Malaga

Locations

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

Málaga, Malaga, Spain

Countries

Spain

References

Orgogozo JM, Rigaud AS, Stoffler A, Mobius 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. doi: 10.1161/01.str.0000020094.08790.49.

Reference Type: BACKGROUND

PMID: 12105362 (View on PubMed)

Pantoni L. Treatment of vascular dementia: evidence from trials with non-cholinergic drugs. J Neurol Sci. 2004 Nov 15;226(1-2):67-70. doi: 10.1016/j.jns.2004.09.014.

Reference Type: BACKGROUND

PMID: 15537523 (View on PubMed)

Roman G. Perspectives in the treatment of vascular dementia. Drugs Today (Barc). 2000 Sep;36(9):641-53. doi: 10.1358/dot.2000.36.9.593781.

Reference Type: BACKGROUND

PMID: 12847569 (View on PubMed)

Other Identifiers

Gabinete Berthier y Martínez.

Identifier Type: -

Identifier Source: secondary_id

Lundbeck, Spain, S.A.

Identifier Type: -

Identifier Source: secondary_id

M-10830

Identifier Type: -

Identifier Source: org_study_id