Augmenting Language Therapy for Aphasia: Levodopa

Phase 2

Completed

Conditions: Nonfluent Aphasia
Stroke

Interventions: Drug: Placebo comparator
Drug: levodopa/carbidopa

Registration Number: NCT01429077

Lead Sponsor: Shirley Ryan AbilityLab

Brief Summary: The purpose of this study is to evaluate the effectiveness of the medication levodopa, in combination with speech-language treatment, on the language outcome of study subjects with nonfluent aphasia (i.e. difficulty with the comprehension and expression of spoken and written language) following a stroke.

Detailed Description: Stroke is the third leading cause of death and the most common cause of disability in the United States. According to the American Stroke Association, the prevalence of stroke in the U.S. is approximately 4.8 million with approximately 700,000 additional strokes occurring annually. Approximately 150,000 to 250,000 stroke survivors becoming severely and permanently disabled each year.

A common neurological deficit among stroke survivors, and thus a substantial contributor to post-stroke disability, is aphasia. The loss of, or difficulty with language is extremely debilitating and has enormous social and economic impact on quality of life. Presently, the only treatment available for persons with aphasia is speech-language rehabilitation.

With rehabilitation only, however, many patients achieve a less than satisfactory improvement in speech-language function, and thus are left with significant disability.

To enhance motor and language recovery in patients with neurological impairments, interest in the use of novel biological therapies, including pharmacological agents, has recently emerged. There is preliminary evidence that increased levels of dopamine, in combination with language treatment, may improve the deficits of aphasia following stroke. Most studies have investigated the adjunctive effects of the dopamine agonist bromocriptine, with mixed results. However, new evidence is suggesting that levodopa, a precursor to dopamine, may be more effective in promoting language learning.

This study proposes to evaluate the effectiveness of levodopa in study subjects with Broca's aphasia after stroke, delivered concurrent with speech-language rehabilitation.

The language changes in subjects who receive speech and language therapy combined with levodopa will be compared to that of subjects who receive the same speech-language rehabilitation but with a placebo (i.e. a pill that does not contain the study drug, levodopa). The two study groups will be compared to determine the degree to which improvements in language performance occur and the degree to which they are maintained over time.

The protocol is double-blind: neither subjects nor researchers will know whether a subject took levodopa or placebo until the study's conclusion.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 36

Inclusion Criteria

A single unilateral left-hemisphere stroke
Nonfluent aphasia, with a mean length of utterance of 0-4 words and an Aphasia Quotient between 20 and 75 on the Western Aphasia Battery
Age 21 or older.
At least 6 months post-stroke
Able to comply with the study protocol
Premorbidly right-handed, as determined by the Edinburgh Handedness Inventory
Fluent in English premorbidly
Completed at least 8th grade education

Exclusion Criteria

More than one stroke
Any other neurological condition that could potentially affect cognition or speech.
Global aphasia or inability to participate in routine speech therapy.
Major active psychiatric illness that may interfere with required study procedures.
Untreated or inadequately treated depression.
Has started taking a potentially confounding central nervous system (CNS) drug within the previous 2 months.
Current abuse of alcohol or drugs
Nursing a child or pregnant
Participation in another drug, device or biologics trial within the preceding 90 days
Unable to understand, cooperate or comply with study procedures
Significant visual or auditory impairment
History of sensitivity to ergot derivatives.
Active medical illness or current medication that precludes safe participation in this study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Inactive pill	Placebo comparator	The placebo comparator (inactive pill) is received orally 30-45 minutes before 1 hour of speech-language treatment, five days a week, for six weeks.
Levodopa/carbidopa	levodopa/carbidopa	The study drug (100 mg levodopa / 25 mg carbidopa), is received orally 30-45 minutes before 1 hour of speech-language treatment, five days a week, for six weeks.

Primary Outcome Measures

Name	Time	Method
Language Quotient (LQ) on the Western Aphasia Battery	Change from Baseline in Western Aphasia Battery LQ at 6 weeks	Includes a measure of auditory comprehension, oral expression, reading and written expression skills. The scale ranges from 1 - 100 with 100 being better. The change or gain score from baseline to immediately post-treatment (at 6 weeks) is reported. The larger the change score, the greater the improvement.

Secondary Outcome Measures

Name	Time	Method
Western Aphasia Battery Aphasia Quotient (Maintenance)	Change in Western Aphasia Battery AQ from 6 weeks to 12 weeks
Functional Communication Skills	Change from Baseline in functional communication skills at 6 weeks	Scores derived from language sample analyses
Participation in Everyday Activities	Change from Baseline in participation in everyday activities at 6 weeks	Measures on CETI, QCL,BOSS, CCRSA.
Western Aphasia Battery - Reading and Writing Scores	Change from Baseline in Western Aphasia Battery Reading and Writing scores at 6 weeks
Western Aphasia Battery Reading and Writing Scores (Maintenance)	Change in WAB Reading and Writing Skills from 6 weeks to 12 weeks
Functional Communication Skills (Maintenance)	Change in functional communication skills from 6 weeks to 12 weeks
Participation in Everyday Activities (Maintenance)	Change in participation in everyday activities from 6 weeks to 12 weeks