Memantine and Intensive Speech-Language Therapy in Aphasia - Full Text View

Sponsors and Collaborators:	Gabinete Berthier y Martínez H. Lundbeck A/S
Information provided by:	Gabinete Berthier y Martínez
ClinicalTrials.gov Identifier:	NCT00640198

Purpose

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).

Condition	Intervention	Phase
Aphasia Stroke	Drug: memantine Behavioral: constraint-induced language therapy (CIAT) Drug: placebo	Phase IV

MedlinePlus related topics: Aphasia

Drug Information available for: Memantine Memantine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
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.

Further study details as provided by Gabinete Berthier y Martínez:

Primary Outcome Measures:

Language function (overall aphasia severity). [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Depression [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Cognitive evaluation of language function [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Changes in event-related potential [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment:	28
Study Start Date:	March 2005
Study Completion Date:	November 2007
Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group 1 Memantine: Active Comparator Patients included in this group will receive memantine alone followed by memantine combined with intensive speech-language 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) 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).
Group 2: Placebo Comparator Patients included in this group will receive placebo alone followed by memantine combined with intensive speech-language therapy.	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: placebo Placebo

Arms

Assigned Interventions

Group 1 Memantine: Active Comparator

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

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).

Group 2: Placebo Comparator

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

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: placebo

Placebo

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.

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:

Dementia
Major psychiatric illness
Severe global aphasia (precludes participation in constraint-induced language therapy)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00640198

Locations

Spain
Gabinete Berthier y Martínez and Centro de Investigaciones Médico-Sanitarias (CIMES) University of Malaga
Malaga, Spain, 29001

Sponsors and Collaborators

Gabinete Berthier y Martínez

H. Lundbeck A/S

Investigators

Principal Investigator:

Marcelo L. Berthier, M.D., Ph.D

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

More Information

Publications:

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.

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.

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

Study ID Numbers:	M-10830, Gabinete Berthier y Martínez., Lundbeck, Spain, S.A.
Study First Received:	March 17, 2008
Last Updated:	March 20, 2008
ClinicalTrials.gov Identifier:	NCT00640198
Health Authority:	Spain: Ministry of Health and Consumption

Keywords provided by Gabinete Berthier y Martínez:

Aphasia
Memantine
Constraint-induced language therapy
Event-related potentials

Study placed in the following topic categories:

Excitatory Amino Acids
Signs and Symptoms
Speech Disorders
Dopamine
Cerebral Infarction
Aphasia

Stroke
Memantine
Neurologic Manifestations
Language Disorders
Neurobehavioral Manifestations
Communication Disorders

Additional relevant MeSH terms:

Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents
Therapeutic Uses
Physiological Effects of Drugs
Nervous System Diseases

Antiparkinson Agents
Excitatory Amino Acid Agents
Dopamine Agents
Central Nervous System Agents
Pharmacologic Actions
Excitatory Amino Acid Antagonists

ClinicalTrials.gov processed this record on January 14, 2009