Anxiety in Youth with Autism Spectrum Disorder

自闭症谱系障碍青少年的焦虑

• 批准号: 10784337
• 负责人: Robyn P. Thom
• 金额: $ 12.9万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-07 至 2026-01-19
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10784337
• 关键词: Accelerometer; Address; Adolescent; Adverse drug effect; Affect; Aftercare; Agonist; Anxiety; Anxiety Disorders; Applied Research; Autonomic nervous system; Award; Behavioral; Biological Markers; Biometry; Blood Pressure; Buspirone; Child; Childhood; Clinical; Clinical Trials; Clinical Trials Design; Cognitive Therapy; Data; Data Analyses; Development; Dropout; Emotions; Environment; Evidence based treatment; Failure; Familiarity; Funding; Future; General Hospitals; Goals; Grant; Heart Rate; Impairment; Individual; Intellectual functioning disability; Intervention Trial; Knowledge; Laboratories; Leadership; Manuscripts; Massachusetts; Measurement; Measures; Mental disorders; Mentors; Mentorship; Meta-Analysis; Methodology; Methods; Occupational; Parents; Patient Self-Report; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phenotype; Physiological; Placebo Effect; Placebos; Population; Preparation; Principal Investigator; Problem behavior; Psychopharmacology; Psychophysiology; Publishing; Quality of life; Randomized; Randomized, Controlled Trials; Reporting; Research; Risk; Sample Size; Selective Serotonin Reuptake Inhibitor; Serotonin; Severities; Site; Stress; Testing; Training; Treatment outcome; Work; acceptability and feasibility; adolescent with autism spectrum disorder; anxiety reduction; anxiety spectrum disorders; anxiety symptoms; anxiety treatment; autism spectrum disorder; autistic children; biomarker validation; career development; clinical anxiety; clinical efficacy; clinical heterogeneity; cognitive ability; comorbidity; data acquisition; effectiveness testing; effectiveness trial; evidence base; experience; feasibility testing; functional disability; heart rate variability; improved; innovation; medical schools; multi-site trial; novel; preclinical study; psychiatric comorbidity; responsible research conduct; skills; social communication; societal costs; standard care; symposium; therapy development; treatment response; usability

PROJECT SUMMARY/ABSTRACT Anxiety is a common and impairing psychiatric comorbidity affecting up to 70% of youth with autism spectrum disorder (ASD) for which there are very limited evidence-based treatments. Gold-standard treatment approaches including selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT) are often unsuitable, ineffective, or poorly tolerated in youth with ASD. No large scale, well-powered clinical trials of pharmacotherapy for anxiety in ASD have been published. Prior research on anxiety in ASD has key methodological limitations including the lack of high quality clinical endpoints, objective biomarkers, or known mechanisms underlying treatment response. Our long-term goal is to advance the evidence-based treatment for anxiety in youth with ASD by identifying underlying treatment mechanisms and conducting high quality clinical trials. The objectives of this proposal are to (1) identify autonomic nervous system (ANS) measures that can be obtained in youth with ASD which correlate with anxiety severity in the K99 phase (Aim 1) and (2) to conduct a randomized controlled trial of buspirone to preliminarily assess its efficacy (Aim 2) and whether ANS modulation is a target mechanism (Aim 3) in the R00 phase. This contribution is significant since youth with ASD commonly experience anxiety disorders and there are limited evidence-based treatments. The proposed research is innovative in that it will be the first ASD clinical trial to incorporate objective physiologic mechanisms, decreasing overreliance on subject self-/parent-report or clinician rating. Aims of the principal investigator’s K99 career development and training plan include (1) Obtain training and applied experience acquiring and interpreting autonomic nervous system (psychophysiology) data in youth with ASD, (2) Develop expertise in psychopharmacology clinical trials design and execution, (3) Develop familiarity with applied biostatistics relevant to intervention trials, and (4) Advance skills in manuscript preparation, grantsmanship, leadership, and responsible conduct of research. These goals will be achieved through a training plan comprised of mentorship, formal coursework, conferences, and manuscript/grant preparation. Knowledge gained via the training plan will be augmented by the applied research experience. Drs. Christopher McDougle, Kerry Ressler, Sabine Wilhelm, David Eddie, and Caitlin Ravichandran will serve as mentors on this award. Massachusetts General Hospital- Harvard Medical School provides an exceptional environment in which to conduct this training and research. By the end of the R00 period, the principal investigator will have a working methodology for obtaining ANS measures relevant to clinical trials in youth with ASD and anxiety, a preliminary estimate of the placebo effect and buspirone-placebo difference, and sample size needed to more fully test physiologic mechanisms. These will inform a multi-site R01 effectiveness trial of buspirone or other anti-anxiety medications. The principal investigator will also have the training and experience needed to successfully obtain R61/R33 funding to test novel agents that are either in active development or repurposed non-CNS agents for anxiety in this population.

项目摘要/摘要 焦虑是一种常见且损害的精神病合并症，影响多达70％的自闭症年轻人 疾病（ASD）的基于证据的治疗非常有限。金标准治疗方法 包括选择性5-羟色胺再摄取抑制剂（SSRI）和认知行为疗法（CBT）通常是 在ASD的年轻人中，不合适，无效或耐受性不佳。没有大规模的，有力的临床试验 ASD中的动画药物疗法已出版。先前关于ASD动画的研究具有关键 方法论上的局限性包括缺乏高质量临床终点，客观生物标志物或已知的 治疗反应的基础机制。我们的长期目标是推进基于证据的治疗 通过识别潜在的治疗机制并进行高质量临床，ASD青年的焦虑 试验。该提议的目标是（1）确定可以是可以是的自主神经系统（ANS）措施 在ASD的青年中获得与K99阶段（AIM 1）和（2）进行焦虑严重程度相关的ASD。 胰蛋白的随机对照试验初步评估其有效性（AIM 2）以及ANS调制是否 是R00阶段中的目标机制（AIM 3）。这项贡献很重要，因为ASD的青年通常 经历动画障碍，基于证据的治疗有限。拟议的研究是 创新的是，这将是首次结合客观生理机制的ASD临床试验 对主题/家长报告或临床等级的过度依赖。主要研究者K99职业的目的 开发和培训计划包括（1）获得培训和应用经验 ASD年轻人的自主神经系统（心理生理学）数据，（2）发展专业知识 心理药理学临床试验设计和执行，（3）与应用生物统计学相关的熟悉程度 进行干预试验，以及（4）手稿准备，授予技巧，领导和 负责任的研究。这些目标将通过完成Mentalship的培训计划来实现， 正式的课程，会议和手稿/赠款准备。通过培训计划获得的知识将 被应用研究经验增强。博士。 Christopher McDugle，Kerry Ressler，Sabine Wilhelm， 大卫·埃迪（David Eddie）和凯特琳·拉维坎德兰（Caitlin Ravichandran）将担任该奖项的导师。马萨诸塞州总医院 哈佛医学院提供了一个特殊的环境，可以在其中进行培训和研究。经过 在R00期的结束时，主要研究人员将有一种工作方法来获得ANS措施 与ASD和动画青年的临床试验有关，对安慰剂效应的初步估计和 Buspirone-placebo差异和样本量需要进行更全面的生理机制。这些会 告知丁螺酮或其他抗焦虑药的多站点R01有效性试验。校长 调查人员还将获得成功获得R61/R33资金进行测试所需的培训和经验 在积极开发或重新利用的非CNS代理中用于该人群中的动画的新型药物。