Metabolic Effects of Antipsychotics in Children
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 144
- 试验地点
- 1
- 主要终点
- Change in Insulin-stimulated Glucose Rate of Disappearance (Glucose Rd)
研究概览
简要总结
The project aims to describe and compare the outcome of 12 weeks of prospective, randomized treatment with olanzapine, risperidone or aripiprazole on insulin action in skeletal muscle, liver and adipose tissue, abdominal fat mass, total body and fat-free mass, efficacy for symptoms of aggression and non-metabolic adverse events. Children aged 6-18 will be studied, exploring effects of stimulant therapy and age-related differences in vulnerability to treatment-induced adverse metabolic changes. Aims are addressed by measuring glucose and lipid kinetics with stable isotope tracers, body composition with dual energy x-ray absorptiometry and magnetic resonance imaging (MRI), and standardized assessments of efficacy and adverse events. Relevant data are critically needed to target clinical therapy and basic research, identify medical risks, and guide regulatory decisions in this vulnerable population.
详细描述
This randomized clinical trial assesses both the safety and efficacy of atypical antipsychotic agents in antipsychotic-naive aggressive children with various childhood psychiatric disorders during 12 weeks of prospective, randomized treatment with olanzapine, risperidone or aripiprazole.
Aim 1: To evaluate effects of selected antipsychotic treatments on insulin action in muscle (glucose disposal), liver (glucose production) and adipose tissue (lipolysis).
Aim 2: To evaluate effects of selected antipsychotic treatments on abdominal fat mass, total body fat and total fat-free mass.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 6-18 years
- •Generally healthy and a score of ≥ 18 on the Aberrant Behavior Checklist in the context of one or more Axis I Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) childhood psychiatric disorders, including conduct disorder, oppositional defiant disorder, disruptive behavior disorder, autism, pervasive developmental disorder, attention deficit disorder, schizophrenia and bipolar affective disorders
- •Children's Global Assessment Scale (CGAS) score ≤ 60
- •Not previously treated with an antipsychotic; individual subjects with remote, brief prior antipsychotic exposure may be considered for enrollment by the PI on a case by case basis
- •Patient assent and informed consent obtained from the parent or guardian
- •No clinically significant (based on PI determination) changes in permitted medications (e.g., stimulants and selective serotonin reuptake inhibitors [SSRIs]) for approximately 1 month prior to Baseline evaluations
排除标准
- •Active suicidality or primary dx of major depressive disorder
- •Any lifetime use of antipsychotics or non-serotonin selective reuptake inhibitor (non-SSRI) anti-depressants
- •The presence of any serious medical disorder, based on PI determination, that may confound the assessment of relevant biologic measures or diagnoses, including:
- •significant organ system dysfunction;
- •endocrine disease, including type 1 or type 2 diabetes mellitus;
- •coagulopathy;
- •or acute infection.
- •Subjects regularly taking any glucose lowering agent, lipid lowering agent, exogenous testosterone, recombinant human growth hormone, or any other endocrine agent that might confound substrate metabolism, oral glucocorticoids (glucocorticoid inhalants and nasal sprays are permitted), antihistamines, sedating antihistamines (non-sedating antihistamines such as but not limited to Claritin (loratadine) and Zyrtec (cetirizine) are permitted), and certain mood stabilizing agents, as some medications may themselves worsen or otherwise alter weight gain, glucose and lipid regulation or otherwise make it difficult to assess the effects of the antipsychotic alone; (note that exposure to many psychotropic agents including stimulants and SSRI's is permitted in order to maintain the generalizability of the sample);
- •Intelligence quotient (IQ) < 70 (based on school records and/or evaluation by clinician)
- •current substance abuse
- •Past history or currently has dyskinesia
- •Stimulant dosage significantly higher (per PI judgment)than the equivalent of approximately 2mg/kg/day methylphenidate equivalent dose.
研究组 & 干预措施
aripiprazole
Participants in this group will be randomized to flexibly-dosed treatment with aripiprazole.
干预措施: aripiprazole (Drug)
olanzapine
Participants in this group will be randomized to flexibly-dosed treatment with olanzapine.
干预措施: olanzapine (Drug)
risperidone
Participants in this group will be randomized to flexibly-dosed treatment with risperidone.
干预措施: risperidone (Drug)
结局指标
主要结局
Change in Insulin-stimulated Glucose Rate of Disappearance (Glucose Rd)
时间窗: 12 weeks
This study hypothesized that antipsychotic treatment would decrease insulin sensitivity at muscle, as measured by the insulin-stimulated rate of disappearance of glucose (glucose Rd), with larger adverse effects for olanzapine.
Change in DEXA % Body Fat
时间窗: 12 weeks
This study hypothesized that antipsychotic treatment would increase percent total body fat, as measured by whole body dual energy x-ray absorptiometry (DEXA), with larger adverse effects for olanzapine.
次要结局
- Change in MRI-measured Visceral Abdominal Fat(12 weeks)
- Change in MRI-measured Subcutaneous Abdominal Fat(12 weeks)
- Change in Insulin-stimulated Glycerol Rate of Appearance (Glycerol Ra)(12 weeks)
- Change in Insulin-stimulated Glucose Rate of Appearance (Glucose Ra)(12 weeks)