FLUOXETINE vs. PLACEBO IN CHILD/ADOLESCENT AUTISTIC DISORDER

氟西汀与安慰剂治疗儿童/青少年自闭症

• 批准号: 7560787
• 负责人: ERIC HOLLANDER
• 金额: $ 29.99万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7560787
• 关键词: Accounting; Acute; Adolescent; Adverse effects; Anxiety; Autistic Disorder; Autoreceptors; Behavior; Blood; Brain region; CYP2D6 gene; Candidate Disease Gene; Cells; Child; Chromosomes, Human, Pair 17; Clinical; Clinical Trials; Complex; Cytochrome P-450 CYP2D6; Data; Dose; Double-Blind Method; Etiology; Exons; Fluoxetine; Genes; Genetic Polymorphism; Genetic Variation; Genotype; HTR2A gene; Individual; Introns; Knowledge; Left; Liquid substance; Maintenance; Mediating; Mediator of activation protein; Mental Depression; Minisatellite Repeats; Molecular Genetics; Neurons; Neurotransmitters; Patients; Peptides; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Promoter Regions; Publishing; Randomized; Rate; Relapse; Relative (related person); Sampling; Selective Serotonin Reuptake Inhibitor; Serotonin; Serotonin Receptor 5-HT1B; Serotonin Receptor 5-HT2A; Severities; Severity of illness; Symptoms; Synaptic Cleft; System; Time; Tryptophan 5-monooxygenase; Up-Regulation; Variant; Week; Work; autistic children; base; depressive symptoms; disorder subtype; functional disability; genetic association; genetic variant; improved; insertion/deletion mutation; postsynaptic; presynaptic; response; reuptake; serotonin transporter; treatment trial

While fluoxetine is frequently prescribed to autistic patients in clinical practice, its efficacy, side effects, maintenance and discontinuation effects have not been definitively established. Mixed results of efficacy, particularly between pre- and post-pubertal patients, and a lack of well-controlled trials leave many gaps in our knowledge about SSRIs, such as fluoxetine, in autism. Furthermore, it is important to determine whether specific subtypes of individuals (those with increased repetitive behaviors), or those with specific genetic variants or polymorphisms of the serotonin system respond differentially to fluoxetine. Little controlled data is available with medications that target the repetitive behavior domain of autism, which contributes to substantial functional impairment. This study will compare liquid fluoxetine vs. placebo in treating child/adolescent autistic patients and assess the relationship between dose, blood levels and response to treatment. The relationship between candidate genes of the serotonin system, symptom improvement, and side effects will be examined. The study will consist of three treatment phases: Phase 1 - a 12-week doubleblind placebo-controlled parallel acute treatment phase, Phase 2 - a 12-week treatment extension phase, and Phase 3 - a 12-week double-blind placebo-controlled discontinuation phase. We aim to evaluate a targeted treatment of a core symptom domain in a stratified sample of autistic children with repetitive behavior, and explore the relationship between genetic variation of the 5-HT system and fluoxetine treatment response and side effects.

虽然在临床实践中经常向自闭症患者开处方，但尚未确定其功效，副作用，维护和中断效应。疗效的结果混合了，特别是前和后患者之间的疗效结果，缺乏控制良好的试验在自闭症中对SSRI（例如氟西汀）的知识差距很多。此外，重要的是要确定个体的特定亚型（重复行为增加），或那些具有特定遗传变异或多态性的特定的亚型对5-羟色胺系统的特定亚型对氟西汀的反应差异很大。针对自闭症的重复行为领域的药物几乎没有受控数据，这有助于 实质性功能障碍。这项研究将比较液体氟西汀与安慰剂治疗 儿童/青少年自闭症患者，并评估剂量，血液水平和对治疗反应之间的关系。将检查5-羟色胺系统的候选基因，症状改善和副作用之间的关系。该研究将包括三个治疗阶段：第1阶段 - 为期12周的双盲安慰剂对照平行急性治疗阶段，第2阶段 - 一个为12周的治疗延伸阶段，第3阶段 - 一个为期12周的双盲安慰剂对照阶段。我们旨在评估对具有重复行为的自闭症儿童的分层样本的核心症状领域的有针对性治疗，并且 探索5-HT系统的遗传变异与氟西汀治疗反应与副作用之间的关系。