2/3-Improving Metabolic Parameters of Antipsychotic Child Treatment

描述（由申请人提供）：本合作R 01申请题为“改善抗精神病药物儿童治疗的代谢参数”（IMPACT），是为了响应NIMH PA-07-092（精神障碍、艾滋病和酒精使用障碍临床和服务研究的合作R 01）和PA-07-078（精神药物治疗后出现的不良反应）而重新提交的。这项为期五年的三个地点的研究将在约翰霍普金斯大学/马里兰州大学（M。里德尔PI），北卡罗来纳州大学（L。Sikich PI）和Zucker希尔赛德医院（C。Correll PI）。总体目标是为使用第二代抗精神病药物（SGAs）体重增加的儿童和青少年确定更好的治疗方法。“改善的治疗”将：1）提供足够的精神症状缓解，2）减少SGA诱导的体重增加，和3）减少SGA诱导的胰岛素抵抗和高脂血症。肥胖、胰岛素抵抗和高脂血症的减少具有重大的公共卫生重要性，因为它们是与2型糖尿病和早发心血管疾病密切相关的因素。拟议研究的具体目的是获得与对照治疗相比，2种药物治疗策略在减少青年人SGA相关体重增加和代谢问题方面的相对风险和获益数据。这项研究建立在广泛的试点数据的基础上，将使用混合疗效/有效性设计来评估两种竞争性药物治疗方法，用于管理服用SGAs的青少年的体重增加和代谢副作用。这项研究的设计是为了使研究结果可以推广到其他临床环境。我们计划招募240名参与者，年龄在8-17岁之间，他们：1）目前正在接受三种最常用的抗精神病药物之一的治疗2）当前BMI >第85百分位数，并且在过去一年中在用其当前SGA治疗时经历了显著的体重增加（>10%），3）符合精神分裂症谱系障碍或双相型谱系障碍的DSM-IV诊断标准，以及4）精神病学稳定。所有受试者将被随机分配至三种情况之一：1）继续当前SGA（对照组），2）二甲双胍+当前SGA，或3）交错转换为阿立哌唑并停止当前SGA。本研究将包括3周筛选/基线期和24周治疗。主要结果变量是体重变化，如BMI z评分变化所反映。次要结局包括：BMI百分位数变化、体重变化（基线体重百分比）、体脂量、胰岛素敏感性、血脂、代谢综合征患病率和所有原因治疗中止。经历持续过度体重增加或精神不稳定的个体将从试验中移除，并根据研究小组的临床指征进行治疗。该项目的结果将为今后治疗患有严重精神疾病的儿童和青少年提供信息。研究结果也可能导致改善他们健康和长寿的治疗方法。

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.