1/3-Improving Metabolic Parameters of Antipsychotic Child Treatment (IMPACT)

描述(申请人提供)：这份名为“改善抗精神病儿童治疗的代谢参数”(IMPACT)的合作R01申请是根据NIMH PA-07-092(精神疾病、艾滋病和酒精使用障碍的临床和服务研究合作R01)和PA-07-078(治疗-精神药物的紧急不良反应)重新提交的。这项为期五年、三个地点的研究将在约翰·霍普金斯大学/马里兰大学(M.里德尔·皮)、北卡罗来纳大学(L.Sikich Pi)和扎克·希尔赛德医院(C.Correll Pi)进行。首要目标是为服用第二代抗精神病药物(SGA)体重大幅增加的儿童和青少年确定改进的治疗方法。一种“改进的治疗”将：1)提供足够的精神症状缓解，2)减少SGA引起的体重增加，3)减少SGA引起的胰岛素抵抗和高脂血症。减少肥胖、胰岛素抵抗和高脂血症对公众健康具有重要意义，因为它们是与2型糖尿病和过早心血管疾病密切相关的因素。这项拟议研究的具体目标是获得与对照治疗相比，减少青少年SGA相关体重增加和代谢问题的两种药物策略的相对风险和益处的数据。这项研究建立在广泛的试点数据基础上，将使用混合功效/有效性设计来评估两种相互竞争的药物方法，这些方法用于管理SGA上青少年的体重增加和代谢副作用。这项研究旨在将研究结果推广到其他临床环境。我们计划招募240名8-17岁的参与者，他们：1)目前正在接受三种最常用的抗精神病药物(利培酮、奎硫平或奥氮平)之一的治疗，2)目前的BMI&gt；85百分位数，并在过去一年中在接受目前的SGA治疗时体重大幅增加(&gt；10%)，3)符合DSM-IV精神分裂症谱系障碍或双相情感谱系障碍的诊断标准，以及4)精神状态稳定。所有参与者将被随机分成三种情况之一：1)继续目前的SGA(对照组)，2)二甲双胍+当前SGA，或3)交错切换到阿立哌唑并停止目前的SGA。这项研究将包括3周的筛查/基准期和24周的治疗。主要的结果变量是体重的变化，由BMI z分数的变化反映出来。次要结果包括：体重指数百分位数的变化，体重作为基线体重百分比的变化，身体脂肪质量，胰岛素敏感性，血脂，代谢综合征的患病率，以及所有原因停止治疗。体重持续过度增加或精神不稳定的个人将被从试验中移除，并按照研究小组的临床指示进行治疗。该项目的结果将为未来对患有严重精神障碍的儿童和青少年的治疗提供参考。这一结果还可能导致改善他们的健康和寿命的治疗。

DESCRIPTION (provided by applicant): This collaborative R01 application, entitled "Improving Metabolic Parameters of Antipsychotic Child Treatment" (IMPACT), is re-submitted in response to NIMH PA-07-092 (Collaborative R01s for Clinical and Services Studies of Mental Disorders, AIDS and Alcohol Use Disorders) and PA-07-078 (Treatment-Emergent Adverse Effects of Psychotropic Medication). This five-year, three-site study will be conducted at Johns Hopkins University/University of Maryland (M. Riddle PI), University of North Carolina (L. Sikich PI) and Zucker Hillside Hospital (C. Correll PI). The overarching goal is to identify improved treatments for children and adolescents who have gained substantial weight on 2nd generation antipsychotic medications (SGAs). An "improved treatment" would: 1) provide adequate psychiatric symptom relief, 2) reduce SGA-induced weight gain, and 3) reduce SGA-induced insulin resistance and hyperlipidemia. Reductions in obesity, insulin resistance and hyperlipidemia are of great public health importance because they are factors strongly associated with type 2 diabetes and premature cardiovascular disease. The specific objective of the proposed study is to obtain data about the relative risks and benefits of 2 medication strategies for reducing SGA-associated weight gain and metabolic problems in youth, in comparison to control treatment. This study, which builds on extensive pilot data, will use a hybrid efficacy/effectiveness design to evaluate two competing medication approaches for the management of weight gain and metabolic side effects in youngsters on SGAs. The study is designed so that findings can be generalized to other clinical settings. We plan to enroll 240 participants, ages 8-17 years, who: 1) are currently treated with one of the three most commonly prescribed antipsychotics (risperidone, quetiapine or olanzapine), 2) have current BMI >85th percentile and have experienced substantial weight gain (>10%) during the past year while treated with their current SGA, 3) meet DSM-IV diagnostic criteria for a schizophrenia spectrum disorder or bipolar spectrum disorder, and 4) are psychiatrically stable. All participants will be randomized to one of three conditions: 1) continue current SGA (control group), 2) metformin + current SGA, or 3) staggered switch to aripiprazole with discontinuation of current SGA. The study will include a 3-week screening/baseline period and 24 weeks of treatment. The primary outcome variable is change in weight as reflected by change in BMI z-score. Secondary outcomes include: change in BMI percentile, change in weight as percent baseline weight, body fat mass, insulin sensitivity, lipids, prevalence of metabolic syndrome, and all cause treatment discontinuation. Individuals who experience continued excessive weight gain or psychiatric destabilization will be removed from the trial and treated as clinically indicated by the research team. The results of this project will inform future treatment for children and adolescents with major psychiatric disorders. The results are also likely to lead to treatments that improve their health and longevity.