2/3-Atomoxetine Placebo and Parent Training in Autism

2/3-托莫西汀安慰剂和自闭症家长培训

• 批准号: 8237016
• 负责人: MICHAEL George AMAN
• 金额: $ 35.07万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8237016
• 关键词: Address; Adolescent; Adverse effects; Adverse event; Attention; Attention deficit hyperactivity disorder; Autistic Disorder; Behavior; Behavior Therapy; Child; Cognitive; Data Analyses; Dose; Double-Blind Method; Exhibits; FDA approved; Fatigue; Healthcare; Home environment; Hyperactive behavior; Maintenance; Measures; Minor; Modeling; Nausea; Neurocognitive; Outcome Measure; Parent-Child Relations; Parents; Performance; Pharmaceutical Preparations; Pharmacology; Placebo Control; Placebos; Population; Procedures; Protein Structure Initiative; Questionnaires; Randomized Clinical Trials; Research; S-nitro-N-acetylpenicillamine; Safety; Schools; Stomach; Strattera; Stress; Subgroup; Symptoms; System; Training; active method; analog; atomoxetine; autism spectrum disorder; behavior measurement; behavior observation; comparison group; experience; follow-up; improved; inattention; neglect; open label; presynaptic; primary outcome; psychopharmacologic; psychosocial; response; standard care; teacher

DESCRIPTION (provided by applicant): There have been relatively few randomized clinical trials of pharmacology for attention-deficit/hyperactivity (ADHD) in children with Autism Spectrum Disorders (ASD). Studies involving stimulant medications have generally found poorer response rates and higher rates of intolerable side effects than in typically developing children with ADHD. Atomoxetine (Strattera) was approved by the FDA in January 2003 for treatment of ADHD. A nonstimulant, it inhibits the presynaptic norephinephrine transporter. There have been only four studies (three open and one small double-blind) examining this medication in children with ASD. Behavioral treatments, such as training parents in the use of behavioral interventions (PMT), are also standard treatments for ADHD in typically developing children. While PMT also has long been used in ASD, it has rarely been studied in combination with psychopharmacologic treatment in this population. This proposal addresses four objectives: a) to conduct a double-blind, placebo-controlled, 10-week parallel-group comparison of atomoxetine (ATX) versus placebo on i) clinician- and parent-rated behavior, ii) direct observations of behavior, iii) cognitive/performance measures of attention, and iv) adverse events in 156 children with ASD (78 treated with ATX, 78 with placebo); b) to conduct a 10-week parallel-group comparison of PMT versus no-PMT on behavioral measures of compliance in 156 children with ASD (78 with PMT, 78 without PMT) c) to conduct a 10-week parallel-group comparison of combined (ATX plus PMT) vs. single treatment (PMT alone) on measures of compliance in 156 children with ASD; and d) to compare the long-term maintenance of efficacy, safety, and tolerability of ATX and PMT via an open-label 6-month extension trial of responders. Medication doses will be titrated against benefit and side effects over the first 6 weeks (ATX to a cap of 1.8 mg/kg/day). PMT will be 10 sessions, 1-1.5 hr. each, modeled on the RUPP Autism Network PMT. Data analyses will capitalize on the power of a 2 x 2 analysis where appropriate. Children with ASD have been neglected in pharmacological research, placing an enormous burden on health care and educational systems. This trial has the potential to provide answers regarding optimal treatment (both psychosocial and pharmacological) for a sizeable subgroup of children with ASD who experience symptoms of over activity and inattention.

描述（由申请人提供）：关于自闭症谱系障碍（ASD）儿童注意缺陷/多动（ADHD）的药理学随机临床试验相对较少。涉及兴奋剂药物的研究通常发现，与患有多动症的典型儿童相比，兴奋剂药物的反应率更低，难以忍受的副作用发生率更高。托莫西汀（Strattera）于2003年1月被FDA批准用于治疗多动症。它是一种非兴奋剂，抑制突触前去甲肾上腺素转运体。只有四项研究（三项开放研究和一项小型双盲研究）检验了这种药物在自闭症儿童中的应用。行为治疗，如训练父母使用行为干预（PMT），也是典型发育儿童多动症的标准治疗方法。虽然PMT也长期用于ASD，但很少研究将其与该人群的精神药物治疗相结合。该提案有四个目标：a)对156名ASD儿童（78名ATX治疗组，78名安慰剂治疗组）进行双盲、安慰剂对照、为期10周的平行组比较：i)临床和父母评价的行为，ii)直接观察行为，iii)注意力的认知/表现测量，iv)不良事件；b)对156名ASD儿童进行为期10周的PMT与非PMT的依从性行为测量平行组比较（78名有PMT， 78名无PMT） c)对156名ASD儿童进行为期10周的联合（ATX + PMT）与单一（PMT单独）治疗的依从性测量平行组比较；d)通过对应答者进行为期6个月的开放标签延长试验，比较ATX和PMT长期维持的有效性、安全性和耐受性。药物剂量将根据前6周的益处和副作用进行滴定（ATX上限为1.8 mg/kg/天）。PMT将是10次，1-1.5小时。每个都以RUPP自闭症网络PMT为模型。数据分析将在适当的情况下利用2 × 2分析的力量。自闭症儿童在药理学研究中一直被忽视，给卫生保健和教育系统带来了巨大的负担。这项试验有可能为大量出现过度活动和注意力不集中症状的ASD儿童亚群提供最佳治疗（心理社会和药理学）的答案。