A CLINICAL TRIAL OF WEIGHT REDUCTION IN SCHIZOPHRENIA

描述（由申请人提供）：肥胖继续对精神分裂症患者的适当管理提出持续挑战。非药物减肥干预措施是一个可行的选择，但其有效性迄今尚未调查。在第二次修订后的重新提交中，我们建议在超重/肥胖的精神分裂症患者中测试短期内减轻体重和长期维持体重的行为计划。增加了拟议研究的样本，并增加了两年的随访期，以检查我们项目的持久性。 在自上次提交以来的中期，我们在从美国12个研究中心招募的另外65名超重/肥胖精神分裂症患者中检查了我们的减肥计划的有效性。在完成该计划的患者中，50%被随机分配到行为治疗组的患者能够从基线减轻4%或更多的体重。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，还观察到心血管健康的人体测量指标（即，BMI、腰围和臀围）与接受行为治疗的患者中4%或更高的体重减轻相关。 我们现在提出了一个随机的，平行组，临床试验，在300超重/肥胖的精神分裂症患者，严格评估我们的治疗效果。将实验治疗与具有相似持续时间和强度的社交技能训练以及常规治疗进行比较。超重但临床稳定的精神分裂症患者将以4：1：1的比例随机分配至行为治疗组，以减轻体重（BT）、社交技能（SS）或常规护理（UC）。BT组和SST组将在14周的时间内分别接受行为干预以减轻体重和社交技能训练（I期）。在这些干预之后，BT组中体重减轻4%的患者将立即参加一项为期24个月的研究，以检查旨在防止体重重新增加的维持治疗的有效性（II期）。在此阶段，患者将被随机分配（2：1）接受加强治疗，每2周一次，或在2年内照常治疗。该研究还将检查抗精神病药物的影响及其与行为治疗的可能相互作用、预测体重减轻的人口统计学和临床因素、体重减轻对生活质量和自尊的影响以及体重减轻与心血管风险因素之间的关系，例如血糖调节、血脂、血压、身体素质和体育锻炼。 这是有史以来第一次尝试进行一项大型随机试验，对精神分裂症患者进行减肥干预和维持减肥，以及减肥对该人群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.