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

3/3-改善抗精神病儿童治疗的代谢参数（IMPACT）

• 批准号: 8114045
• 负责人: CHRISTOPH U CORRELL
• 金额: $ 27.12万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-22 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8114045
• 关键词: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Adverse effects; Age; Antipsychotic Agents; Benefits and Risks; Body fat; Body mass index; Cardiovascular Diseases; Child; Clinical; Clinical Services; Communities; Control Groups; DSM-IV; Data; Diagnostic; Disease; Dual-Energy X-Ray Absorptiometry; Effectiveness; Enrollment; Future; Generations; Glucose; Goals; Health; Hospitals; Hybrids; Hyperlipidemia; Individual; Insulin; Insulin Resistance; LDL Cholesterol Lipoproteins; Lead; Lipids; Longevity; Maryland; Measurement; Measures; Mental disorders; Metabolic; Metabolic syndrome; Metformin; National Institute of Mental Health; Non-Insulin-Dependent Diabetes Mellitus; North Carolina; OGTT; Obesity; Outcome; Participant; Pharmaceutical Preparations; Placebos; Population Study; Prevalence; Public Health; Quality of life; Randomized; Relative Risks; Research; Risperidone; Schizophrenia; Screening procedure; Secondary to; Site; Symptoms; Time; Translations; Triglycerides; United States; Universities; Weight; Weight Gain; Youth; alcohol use disorder; aripiprazole; arm; design; diabetic; electric impedance; experience; improved; indexing; insulin sensitivity; meetings; olanzapine; premature; primary outcome; quetiapine; response; secondary outcome

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.

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 药物）。这项为期五年的三个地点研究将在约翰·霍普金斯大学/马里兰大学（M. Riddle PI），北卡罗来纳大学（L. Sikich Pi）和Zucker Hillside医院（C. Correll PI）进行。总体目标是确定针对第二代抗精神病药（SGA）增强重量的儿童和青少年的改进治疗方法。 “改善的治疗方法”将：1）提供足够的精神症状缓解，2）减少SGA诱导的体重增加，3）降低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降低非常重要，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。拟议研究的具体目标是获得有关与控制治疗相比，与减少SGA相关的体重增加和代谢问题的2种药物策略的相对风险和好处的数据。这项基于广泛的试验数据的研究将使用混合功效/有效性设计来评估两种相互竞争的药物方法，以管理年轻人对SGA的体重增加和代谢副作用的管理。该研究的设计是为了使发现可以推广到其他临床环境。我们计划招募240名8-17岁的参与者，谁：1）目前接受过三种最常见的处方抗精神病药（利培酮，奎捷吡啶或奥氮平）的治疗之一，2）当前的BMI> 85个百分位数，在过去的一年中经历了大量的体重（> 10％），同时使用SGA，同时又有3个）。精神分裂症谱系障碍或双相谱系障碍，4）在精神上稳定。所有参与者将被随机分为三个条件之一：1）继续当前的SGA（对照组），2）二甲双胍 +电流SGA，或3）交换机开关到Aripiprazole，并终止了当前SGA。该研究将包括3周的筛查/基线期和24周的治疗。主要结果变量是重量变化，如BMI Z评分的变化所反映的。次要结果包括：BMI百分位数的变化，重量的变化，基线重量百分比，体内脂肪量，胰岛素敏感性，脂质，代谢综合征的患病率以及所有导致治疗中断。经历持续体重增加或精神病的人将从试验中删除，并被研究小组在临床上对待。该项目的结果将为患有主要精神疾病的儿童和青少年提供未来的治疗。结果也可能导致改善其健康和寿命的治疗方法。