ARIPIPRAZOLE FOR CLOZAPINE ASSOCIATED MEDICAL MORBIDITY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们提出了一个为期8周，安慰剂对照试验的新的抗精神病药物，阿立哌唑，4周的随访，为连续治疗70氯氮平治疗的精神分裂症受试者检查阿立哌唑对血脂和葡萄糖代谢，以及身体成分的影响。 我们还将进行一系列症状量表，以检查联合治疗的临床相关性。 本研究的结果有助于阐明阿立哌唑连续治疗在氯氮平治疗患者中的有效性，以及高脂血症与胰岛素抵抗和体重增加与氯氮平治疗的关系。 主要具体目标： 1.通过在70名氯氮平治疗的精神分裂症受试者中进行为期8周的15 mg阿立哌唑安慰剂对照试验，检查阿立哌唑降低空腹血脂（包括甘油三酯和总胆固醇）的疗效。 2.检查阿立哌唑减肥和降低BMI的疗效。 3.通过检查空腹胰岛素、稳态模型评估-胰岛素抵抗（HOMA-IR）和FSIVGTT的SI、SG的变化，检查阿立哌唑改善胰岛素抵抗和葡萄糖代谢的疗效。 4.分析血脂、体重减轻和胰岛素抵抗改善的潜在反应预测因素，包括基线血脂、体重、年龄、性别、种族、活动水平和吸烟状况。

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, with a 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 weight 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 efficacy 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.