Augmenting Language Therapy for Aphasia: Levodopa

Study Overview
=================
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.

Official Title
-----------------
Augmenting Language Therapy for Aphasia: A Randomized Double-Blind Placebo-Controlled Trial of Levodopa in Combination With Speech-Language Therapy

Conditions
-----------------
Nonfluent Aphasia, Stroke

Intervention / Treatment
-----------------
* Drug: levodopa/carbidopa
* Drug: Placebo comparator


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Levodopa/carbidopa<br>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. | Drug: levodopa/carbidopa<br>* 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.<br>* Other names: Sinemet;|
| Placebo Comparator: Inactive pill<br>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. | Drug: Placebo comparator<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Language Quotient (LQ) on the Western Aphasia Battery | 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. | Change from Baseline in Western Aphasia Battery LQ at 6 weeks | 

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Levodopa, Ischemic Stroke, Aphasia, Speech Rehabilitation