The purpose of this planning grant is to develop the methods and protocols for clinical trials that will evaluate the effectiveness of the pharmacological agent, bromocriptine, on the language outcome of patients with nonfluent aphasia. There is preliminary evidence that bromocriptine (BRC), a dopaminergic agent, can improve specific deficits of aphasia following stroke. However, it has been studied mostly in the chronic phases, and results have been mixed. Furthermore, most studies have used bromocriptine as a monotherapy but there is evidence that BRC may be more effective if given in combination with aphasia language treatment. Carefully designed randomized clinical trials with adequate numbers of patients are needed to adequately explore the optimum timing and duration of BRC for both acute and chronic aphasia, and to assess whether the combination of BRC with speech-language treatment is more effective than either one of them given as a monotherapy. Accordingly, the specific aims of the proposed clinical trials are (1) to assess whether low dose bromocriptine in combination with speech-language treatment results in greater improvements in language performance than speech-language treatment plus placebo; (2) to assess whether the effectiveness of low dose bromocriptine differs depending on the intensity of the speech-and-language treatment with which it is combined; (3) to assess whether any resultant changes in language performance are maintained over time; and (4) to assess whether the maintenance of these language skills is dependent on continued use of bromocriptine. Two randomized double-blind placebo-controlled trials (one for acute and one for chronic aphasia) are proposed, each with the following four arms (1) BRC plus low intensity aphasia treatment; (2) BRC plus high intensity aphasia treatment; (3) BRC placebo plus low intensity aphasia treatment; and (4) BRC placebo plus high intensity aphasia treatment. The primary outcome measure for each comparison in the trials will be the change in the Aphasia Quotient (AQ) score on the Western Aphasia Battery (Kertesz, 1982) from pretreatment to post-treatment. Other language performance and cognitive measures will be collected pre- and post-treatment to provide a comprehensive assessment of the changes in language performance. Language performance will also be measured at three and six months after completion of treatment to answer the secondary questions regarding maintenance of language improvements.
