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 焦虑是一种常见的精神疾病，影响多达70%患有自闭症的青少年 疾病(ASD)，其循证治疗非常有限。黄金标准的治疗方法 包括选择性5-羟色胺再摄取抑制剂(SSRI)和认知行为疗法(CBT) 在患有自闭症的年轻人中不合适、无效或耐受性差。没有大规模的、动力充足的临床试验 治疗自闭症患者焦虑的药物疗法已经发表。ASD患者焦虑的先前研究具有关键意义 方法学上的限制，包括缺乏高质量的临床终点、客观的生物标志物或已知的 治疗反应的潜在机制。我们的长期目标是推进以证据为基础的治疗 通过确定潜在的治疗机制和进行高质量的临床研究来治疗青少年自闭症患者的焦虑 审判。本提案的目标是(1)确定自主神经系统(ANS)措施 在患有自闭症的青年中获得，与K99阶段的焦虑严重程度相关(目标1)和(2)进行 丁螺环酮的随机对照试验，初步评估其疗效(目标2)和ANS是否调制 是R00阶段的目标机制(目标3)。这一贡献是巨大的，因为青少年通常患有自闭症 患有焦虑症，循证治疗有限。拟议的研究是 创新之处在于，这将是第一个结合客观生理机制的ASD临床试验，减少了 过度依赖受试者自我/家长报告或临床医生评级。首席调查员K99职业生涯的目标 发展和培训计划包括：(1)获得培训和应用经验，获得和口译 自闭症青少年的自主神经系统(心理生理学)数据，(2)发展专业知识 精神药理学临床试验的设计和执行，(3)熟悉相关的应用生物统计学 到干预试验，以及(4)提高手稿准备、赠款、领导力和 负责任的研究行为。这些目标将通过由导师制度组成的培训计划来实现， 正式的课程、会议和手稿/助学金的准备。通过培训计划获得的知识将 通过应用研究经验得到加强。尊敬的克里斯托弗·麦克道格尔博士、克里·雷斯勒博士、萨宾·威廉博士， 大卫·埃迪和凯特琳·拉维坎德兰将担任该奖项的导师。马萨诸塞州综合医院 哈佛医学院提供了一个进行这种培训和研究的特殊环境。通过 在R00期间结束时，首席调查员将有一套获得ANS措施的工作方法 与青少年自闭症和焦虑症的临床试验相关，安慰剂效果的初步估计和 丁螺环酮-安慰剂的差异，以及样本大小需要更全面地测试生理机制。这些遗嘱 通知丁螺环酮或其他抗焦虑药物的多点R01有效性试验。校长 调查员还将拥有成功获得R61/R33资金进行测试所需的培训和经验 在这一人群中，正在积极开发或改变非中枢神经系统药物治疗焦虑症的新型药物。