A CLINICAL TRIAL OF WEIGHT REDUCTION IN SCHIZOPHRENIA

描述(由申请人提供)：肥胖继续给精神分裂症患者的适当管理带来持续的挑战。减轻体重的非药物干预提供了一个可行的选择，但其有效性迄今尚未得到研究。在第二次修订的重新提交中，我们建议测试一种行为程序，用于超重/肥胖精神分裂症患者的短期体重减轻和长期体重维持。拟议研究的样本已经增加，并增加了两年的跟踪期，以检查我们计划的持久性。 自上次提交以来的过渡期内，我们从美国12个地点招募了另外65名超重/肥胖的精神分裂症患者，检查了我们减肥计划的有效性。在完成该计划的患者中，50%的患者被随机分配到行为治疗组，他们的体重从基线水平下降了4%或更多。相比之下，对照组(照常治疗)中只有14.3%的患者体重减轻了4%或更多。此外，还观察到，在接受行为治疗的患者中，心血管健康的人体测量指标(即BMI、腰围和臀围)的显著改善与体重减轻4%或更多有关。 我们现在建议对300名超重/肥胖精神分裂症患者进行随机、平行分组临床试验，以严格评估我们的治疗效果。试验性治疗将与社交技能训练进行比较，持续时间和强度类似，并与常规治疗相比较。超重但临床稳定的精神分裂症患者将被随机分配到减肥(BT)、社交技能(SS)或日常护理(UC)的行为治疗中，比例为4：1：1。BT和SST组将在14周内分别接受减肥和社交技能训练的行为干预(第一阶段)紧随这些干预措施后，BT组中体重减轻4%的患者将参加一项24个月的研究，以检验旨在防止体重再次增加的维持治疗的有效性(第二阶段)。在这一阶段，患者将被随机分配(2：1)接受强化治疗，每两周一次，或在为期两年的时间内照常治疗。这项研究还将研究抗精神病药物的效果及其与行为治疗的可能相互作用，预测减肥的人口统计学和临床因素，减肥对生活质量和自尊的影响，以及减肥与心血管危险因素(如血糖调节、血脂、血压、体能和体育锻炼)的关系。 这是有史以来第一次尝试对精神分裂症患者进行减肥和维持减肥干预的大型随机试验，以及减肥对这一人群中心血管危险因素的影响。

DESCRIPTION (provided by applicant): Obesity continues to present ongoing challenges to the adequate management of patients with schizophrenia. Non-pharmacological interventions for weight reduction present a viable option but their effectiveness has not been investigated thus far. In this second revised resubmission, we propose to test a behavioral program for weight reduction in the short term, and weight maintenance in the long term in overweight / obese patients with schizophrenia. The sample for the proposed study has been increased, and a two-year follow up period has been added to examine the durability of our program. In the interim period since the last submission, we have examined the effectiveness of our weight loss program in an additional 65 overweight / obese patients with schizophrenia recruited from 12 sites across the US. Among those who completed the program, 50% of patients who were randomly assigned to behavioral treatment were able to lose 4% or more body weight from baseline. In contrast, only 14.3% of patients in the control group (treatment as usual) lost 4% or more weight. In addition, it was observed that significant improvements in anthropometric measures of cardiovascular health (i.e., BMI, waist and hip circumference) were associated with 4% or greater weight loss among patients who received the behavioral treatment. We now propose a randomized, parallel group, clinical trial in 300 overweight / obese schizophrenia patients to rigorously assess the effectiveness of our treatment. The experimental treatment will be compared to social skills training, of similar duration and intensity, as well as treatment as usual. Overweight but clinically stable schizophrenia patients will be randomly assigned to behavioral treatment for weight reduction (BT), social skills (SS), or usual care (UC), in the ratio 4:1:1. The BT and SST groups will receive behavioral interventions for weight reduction and social skills training respectively over a 14-week period (Phase I) Immediately following these interventions, patients in the BT group who achieve 4% of higher weight loss will enrolled in a 24 month study examining the effectiveness of a maintenance treatment aimed at preventing weight re-gain (Phase II). In this phase, patients will be randomly assigned (2:1) to either receive booster treatments, one every 2 weeks, or treatment as usual over a 2 year duration. The study will also examine the effects of antipsychotic medications and their possible interaction with the behavioral treatment, demographic and clinical factors predictive of weight loss, effects of weight loss on quality of life and self esteem and the relationship between weight loss and cardiovascular risk factors such as glucose regulation, serum lipids, blood pressure, physical fitness and physical exercise. This is the first attempt ever to conduct a large randomized trial of an intervention for weight reduction, and maintenance of weight loss, in schizophrenia, and of the effects of weight reduction on cardiovascular risk factors in this population.