This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose a 8-week, placebo-controlled trial of the novel antipsychotic agent, aripiprazole, witha 4-week follow-up, for the adjunctive therapy in 70 clozapine treated schizophrenia subjects to examine aripiprazole's affect on lipid and glucose metabolism, as well as body composition. We will also perform a battery of symptoms scales to exam clinical correlates of combination therapy. The results of this study should help clarify the usefulness of adjunctive therapy with aripiprazole in clozapine-treated patients and the relationship of hyperlipidemia to insulin resistance and wight gain with clozapine treatment. Primary Specific Aims: 1. Examine the efficacy of aripiprazole for reducing fasting lipids, including triglycerides and total cholesterol, by conduction an 8-week placebo controlled trial of 15 mg aripiprazole in 70 clozapine-treated schizophrenia subjects. 2. Examine the ifficacy of aripiprazole for weight loss and BMI reduction. 3. Examine the efficacy of aripiprazole for improving insulin resistance and glucose metabolism measured by examining changes in fasting insulin, homeostatic model assessment-insulin resistance (HOMA-IR), and SI, SG from FSIVGTT. 4. Analyze potential predictors of response for improvements in lipids, weight loss, and insulin resistance, including baseline lipids, weight, age, gender, race, activity levels and smoking status.
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