Memantine and Intensive Speech-Language Therapy in Aphasia

Condition(s) targeted: Aphasia; Stroke

Intervention: memantine (Drug); constraint-induced language therapy (CIAT) (Behavioral); memantine (Drug); placebo (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Gabinete Berthier y Martínez

Official(s) and/or principal investigator(s):
Marcelo L. Berthier, M.D., Ph.D, Principal Investigator, Affiliation: Gabinete Berthier y Martínez and Centro de Investigaciones Médico-Sanitarias (CIMES), University of Malaga

- 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).

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.

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

Primary outcome: Language function (overall aphasia severity).

Secondary outcome:

Depression

Cognitive evaluation of language function

Changes in event-related potential

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.

Minimum age: 18 Years. Maximum age: 69 Years. Gender(s): Both.

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)

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

Related publications:

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.

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.

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

Starting date: March 2005
Last updated: March 20, 2008