CLINICAL TRIAL: TREATMENT OF SLEEP PROBLEMS IN CHILDREN WITH AUTISM SPECTRUM DIS

临床试验：自闭症谱系障碍儿童睡眠问题的治疗

• 批准号: 7950650
• 负责人: BOBBI HOPKINS
• 金额: $ 0.68万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7950650
• 关键词: Address; Affect; Aftercare; Age; Autistic Disorder; Behavior; Behavioral; Child; Circadian Rhythms; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Cognitive; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Diagnostic tests; Disease; Dose; Double-Blind Method; Effectiveness; Evaluation; Exposure to; Family; Functional disorder; Funding; Future; Gastroesophageal reflux disease; Goals; Grant; Hormones; Hour; Individual; Institution; Intervention; Life; Matched Group; Measures; Medical; Melatonin; Oral; Outcome Measure; Parents; Participant; Pharmaceutical Preparations; Phase; Placebos; Play; Production; Quality of life; Questionnaires; Randomized Controlled Clinical Trials; Recruitment Activity; Research; Research Personnel; Research Project Grants; Resources; Role; Salivary; Sampling; Severities; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Sleep disturbances; Sleeplessness; Source; Structure; Symptoms; Testing; United States National Institutes of Health; Urine; actigraphy; autism spectrum disorder; experience; hypnotic; improved; primary outcome; response; treatment trial

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose to examine whether sleep problems in children with autism spectrum disorder (ASD) are related to alterations in the secretion of melatonin (MT), a hormone that plays an important role in regulating the circadian cycle and sleep. Furthermore, we will examine the efficacy of MT for improving sleep in children with ASD. Children with ASD experience high rates of sleep disturbances that potentially contribute to the severity of their cognitive and behavioral dysfunction and to poor quality of life for themselves and their families. It is unclear if irregularities in MT rhythm underlie sleep problems in children with ASD. Their sleep problems are characterized by sleep-wake rhythm abnormalities and symptoms of insomnia including difficulty initiating and maintaining sleep. MT is frequently used to treat these sleep problems; however, its effectiveness as a hypnotic to treat insomnia in children with ASD has not been clearly established. All subjects will be recruited from the Autism Treatment Network after completing rigorous diagnostic testing. Exclusionary criteria include exposure to melatonin in the month prior to the study, current psychoactive medications or medications known to suppress MT secretion, other sleep disorders, such as sleep apnea, and medical disorders that may affect sleep, such as gastroesophageal reflux disease (GERD). Participants' parents will complete a validated sleep questionnaire, which will define the presence or absence of sleep problems. MT onset will be determined by measuring salivary MT levels before and after usual bedtime in ASD children with sleep problems and in a matched group of children with ASD and no sleep problems. Total 24 hour MT production will be determined from urine samples in these same two groups. A double-blind, randomized trial of three oral doses of MT (3, 6, 9 mg) and placebo in children (ages 4-9 years) with ASD and sleep problems will follow a baseline sleep and behavior evaluation. The primary outcome measure will be change in sleep latency as determined by actigraphy at baseline and at the end of the fifth week of each of the treatment trials. Another primary outcome measure will be change in validated behavioral questions given at baseline and during the fifth week of each of the treatment trials. Results from this study will provide a rationale for the development of future trials of circadian rhythm interventions and clinical parameters for the use of MT to manage sleep problems in ASD. Our hypotheses concerning MT are: 1. Children with ASD and sleep problems will have a delay in MT onset and/or have decreased MT secretion over 24 hours; 2. Oral MT will be associated with improvement in sleep and behavior in children with ASD and sleep problems. SPECIFIC AIMS: This is a proposal to study the relationship between melatonin (MT) and sleep problems in children with autism spectrum disorder (ASD), as part of the collaborative research structure of the Autism Treatment Network (ATN). A major goal of the ATN is to conduct clinical research that will have a significant impact on the daily lives and functioning of individuals with ASD and to address immediate concerns of parents. Children with ASD experience high rates of sleep disturbance, which likely contribute to the severity of their daytime cognitive and behavioral dysfunction and to poorer quality of life for them and their families. As a step toward addressing sleep problems in ASD, we propose to test two hypotheses. Our first hypothesis proposes that children with ASD and sleep problems will have a delay in MT onset and/or have decreased MT secretion over 24 hours. Our second hypothesis proposes that administration of exogenous MT will result in a decrease in sleep problems and a subsequent improvement in daytime behaviors, with higher doses showing greater effect. This research project has the following specific aims: Specific Aim 1: Characterize the endogenous MT profiles in children with ASD with and without sleep problems. Specific Aim 2: Determine the efficacy of MT used as a hypnotic for improving sleep directly and secondarily improving daytime behavior in children with ASD and sleep problems. We predict that results from this study will reveal lower levels of metabolized MT in children with ASD and sleep problems when compared to ASD children without sleep problems. In addition, we anticipate that children with ASD and sleep problems will have delayed MT onset or altered circadian phase. We predict that participants will experience improved sleep after treatment with oral MT, as indicated by shortened sleep latency. We anticipate that children with altered circadian phase will show better response to treatment with MT. We predict that participants who experience improved sleep will demonstrate improved daytime behaviors as a result of their improved sleep. Data from this study will provide important information concerning circadian rhythm dysregulation in ASD and will support the development of future studies using MT to modify and correct abnormal circadian rhythms.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们建议检查自闭症谱系障碍 (ASD) 儿童的睡眠问题是否与褪黑激素 (MT) 分泌的改变有关，褪黑激素 (MT) 是一种在调节昼夜节律和睡眠中发挥重要作用的激素。此外，我们将研究 MT 对于改善 ASD 儿童睡眠的功效。患有自闭症谱系障碍的儿童睡眠障碍的发生率很高，这可能会导致他们严重的认知和行为功能障碍，并导致他们自己和家人的生活质量下降。 目前尚不清楚 MT 节律不规则是否是 ASD 儿童睡眠问题的根源。他们的睡眠问题的特点是睡眠-觉醒节律异常和失眠症状，包括难以启动和维持睡眠。 MT 经常用于治疗这些睡眠问题；然而，其作为催眠药治疗自闭症儿童失眠的有效性尚未明确。 所有受试者在完成严格的诊断测试后都将从自闭症治疗网络招募。 排除标准包括在研究前一个月接触褪黑激素、当前服用精神活性药物或已知抑制 MT 分泌的药物、其他睡眠障碍（例如睡眠呼吸暂停）以及可能影响睡眠的内科疾病（例如胃食管反流病 (GERD)） 。 参与者的父母将完成一份经过验证的睡眠调查问卷，该调查问卷将确定是否存在睡眠问题。 MT 的发作将通过测量有睡眠问题的 ASD 儿童和匹配的患有 ASD 但没有睡眠问题的儿童在正常就寝时间之前和之后的唾液 MT 水平来确定。 24 小时 MT 总产量将根据这两组的尿样确定。对患有自闭症谱系障碍 (ASD) 和睡眠问题的儿童（4-9 岁）进行三种口服剂量的 MT（3、6、9 毫克）和安慰剂的双盲、随机试验，随后将进行基线睡眠和行为评估。主要结果指标是睡眠潜伏期的变化，通过基线和每个治疗试验第五周结束时的体动记录仪确定。另一个主要结果指标是在基线和每次治疗试验的第五周期间给出的经过验证的行为问题的变化。 这项研究的结果将为未来开发昼夜节律干预试验和使用 MT 管理 ASD 睡眠问题的临床参数提供依据。 我们关于 MT 的假设是： 1. 患有自闭症谱系障碍 (ASD) 和睡眠问题的儿童会出现 MT 发作延迟和/或在 24 小时内 MT 分泌减少； 2. 口服 MT 与患有自闭症谱系障碍 (ASD) 和睡眠问题的儿童的睡眠和行为改善有关。 具体目标：这是一项研究褪黑激素 (MT) 与自闭症谱系障碍 (ASD) 儿童睡眠问题之间关系的提案，作为自闭症治疗网络 (ATN) 合作研究结构的一部分。 ATN 的一个主要目标是开展对自闭症谱系障碍患者的日常生活和功能产生重大影响的临床研究，并解决家长的紧迫问题。 患有自闭症谱系障碍的儿童睡眠障碍的发生率很高，这可能会导致他们日间认知和行为功能障碍的严重程度，并导致他们及其家人的生活质量较差。作为解决自闭症谱系障碍睡眠问题的一个步骤，我们建议测试两个假设。 我们的第一个假设提出，患有自闭症谱系障碍 (ASD) 和睡眠问题的儿童 MT 发病时间会延迟和/或 MT 分泌量在 24 小时内减少。 我们的第二个假设提出，施用外源性 MT 将减少睡眠问题，并随后改善日间行为，剂量越高效果越好。 该研究项目有以下具体目标： 具体目标 1：描述有或没有睡眠问题的 ASD 儿童的内源 MT 特征。 具体目标 2：确定 MT 作为催眠药直接改善睡眠并继而改善患有 ASD 和睡眠问题的儿童白天行为的功效。 我们预测，这项研究的结果将显示，与没有睡眠问题的 ASD 儿童相比，患有 ASD 和睡眠问题的儿童的代谢 MT 水平较低。此外，我们预计患有 ASD 和睡眠问题的儿童将出现 MT 延迟或昼夜节律相位改变。我们预测，在口服 MT 治疗后，参与者的睡眠会得到改善，睡眠潜伏期缩短就表明了这一点。我们预计昼夜节律改变的儿童将对 MT 治疗表现出更好的反应。我们预测，睡眠改善的参与者将因睡眠改善而表现出白天行为的改善。 这项研究的数据将提供有关 ASD 昼夜节律失调的重要信息，并将支持未来使用 MT 来修改和纠正异常昼夜节律的研究的发展。