Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors (SOARS-B)

催产素改善自闭症互惠社会行为的研究 (SOARS-B)

• 批准号: 8386309
• 负责人: Linmarie Sikich
• 金额: $ 258.93万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-04 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8386309
• 关键词: 17 year old; Address; Adult; Adverse effects; Age; Animals; Autistic Disorder; Behavior; Behavior Therapy; Behavioral; Binding; Biological; Biological Factors; Brain; Caring; Characteristics; Child; Clinical; Clinical Trials; Cognitive; Communication; Country; Data; Development; Dose; Double-Blind Method; Electrocardiogram; Enrollment; Epigenetic Process; Functional disorder; Future; Genes; Genetic; Goals; Head; Impairment; Incidence; Individual; Intellectual functioning disability; Intervention; Laboratories; Language; Lead; Learning; Methylation; Mission; Motivation; Normal Range; Outcome; Oxytocin; Oxytocin Receptor; Participant; Pathway interactions; Pharmaceutical Preparations; Pilot Projects; Placebos; Play; Randomized; Receptor Gene; Regulation; Rewards; Role; Running; Safety; Sampling; Serious Adverse Event; Severities; Signal Transduction; Site; Social Behavior; Social Problems; Social Values; Speech; Subgroup; Sum; Symptoms; System; Teenagers; Testing; Translating; Treatment Efficacy; Variant; Work; autism spectrum disorder; base; behavior influence; clinically significant; disability; double-blind placebo controlled trial; efficacy trial; evidence base; experience; improved; improved functioning; mRNA Expression; neurobehavioral; novel; open label; phrases; pilot trial; receptor; receptor density; response; skills; social; social communication; social communication impairment; social reciprocity; trait; treatment site; treatment strategy

DESCRIPTION (provided by applicant): This application proposes creation of the ACE SOARS Network and a pivotal clinical trial of sustained oxytocin treatment in children with ASD known as SOARS-B (Study of Oxytocin in ASD to improve Reciprocal Social Behaviors). The ACE SOARS Network consists of five Treatment Sites across the country headed by Chris McDougle (MA), Alex Kolevzon (NY), Bryan King (WA), Lin Sikich (NC) and Jeremy Veenstra-Vander Weele (TN), a Genetic Center run by Simon Gregory (Duke); a Data Center directed by Robert Hamer (UNC); and a Coordinating Center. The mission of the ACE SOARS Network is to develop safe treatments that meaningfully improve functioning and reduce disability for people of all ability levels with autism spectrum disorders (ASD) and to determine factors that predict who will respond to what treatment. The ACE SOARS Network has built on exciting new findings that oxytocin enhances social behavior in people with typical development and ASD and findings from pilot studies of sustained oxytocin treatment in ASD to develop an optimized intranasal form of oxytocin that we expect will be well tolerated. We hypothesize that oxytocin will increase social orienting and the value of social rewards in children with ASD, thus leading to enhanced social motivation and improvement in ASD's core social and communication symptoms. The ACE SOARS Network will rigorously test this hypothesis by conducting SOARS-B, a large (n=300), randomized double-blind, placebo-controlled trial of sustained (6 month), flexibly-dosed intranasal oxytocin treatment for improving reciprocal social behaviors in children 3-17 years old with ASD. We will enroll at least 142 participants who are low-functioning (significant language impairment and intellectual disability with nonverbal IQ < 70) and at least 142 who are high- functioning (fluent phrase speech and nonverbal IQ e 70). After completing double-blind treatment, every participant will be treated with open-label oxytocin for six months to more fully assess safety and functional benefits that may emerge with longer treatment. We will identify clinical characteristics (such as age or verbal fluency) and biological factors (suchas level of methylation of the oxytocin receptor gene - OXTR) that preferentially influence oxytocin response. We also will describe changes in OXTR methylation and mRNA expression of genes relevant to oxytocin signaling in ASD that occur in response to oxytocin or placebo treatment to facilitate future development of novel treatments. In sum, SOARS-B will definitively test oxytocin, an extremely promising biological treatment for ASD's core social symptoms. PUBLIC HEALTH RELEVANCE: PUBLIC HEALTH RELEVANCE This research is relevant to public health and the NIH mission because it rigorously tests whether sustained oxytocin treatment reduces the core social communication symptoms of autism spectrum disorders (ASD). One of every 110 Americans has ASD, which typically persists throughout life and has huge societal costs. We also will identify characteristics that influence oxytocin response to predict who oxytocin is likely to help.

描述（由申请人提供）：本申请提出了ACE SOARS网络的创建，以及对ASD称为SOARS-B的儿童的持续催产素治疗的关键临床试验（ASD中的催产素研究以改善互惠社交行为）。 ACE SOARS网络由克里斯·麦克杜格（MA），亚历克斯·科莱夫宗（Alex Kolevzon），布莱恩·金（Bryan King）（WA），Lin Sikich（NC）和Jeremy Veenstra Vander-Vander-Weele（TN）领导，由Chris McDougle（MA），Alex Kolevzon（MA），Alex Kolevzon（MA）和一个基因中心由Simon Gregory（Duke）经营的五个治疗站点；罗伯特·哈默（Robert Hamer）（UNC）指导的数据中心；和一个协调中心。 ACE飙升网络的使命是开发安全的治疗，以有意义地改善功能并减少自闭症谱系障碍（ASD）的所有能力水平的残疾，并确定预测谁将对哪种治疗做出反应的因素。 Ace Soars网络基于令人兴奋的新发现，即催产素可以增强典型发育和ASD的人的社会行为，以及从ASD中持续的催产素治疗的试验研究中的发现，以开发出优化的鼻内催产素形式，我们希望我们能够很好地容忍。我们假设催产素会增加社会定向和社会奖励对ASD儿童的价值，从而导致社会动机增强和改善ASD的核心社会和沟通症状。 ACE SOARS网络将通过进行SOARS-B（n = 300），随机双盲，安慰剂对照试验的持续（6个月），灵活剂量剂量的催产素治疗方法来严格检验这一假设，以改善3-17岁儿童的互惠社会行为，以改善3-17岁儿童的互惠社交行为。我们将至少注册142名低功能的参与者（具有非语言智商<70的重大语言障碍和智力障碍）和至少有142名高功能高功能（流利的短语语音和非语言智商70）。完成双盲治疗后，每个参与者将用开放标签的催产素治疗六个月，以更全面地评估可能会出现更长的治疗方法的安全性和功能益处。我们将确定临床特征（例如年龄或言语流利性）和生物学因素（类似催产素受体基因的甲基化水平）优先影响催产素反应。我们还将描述与催产素或安慰剂治疗有关的ASD中与催产素信号相关的基因的OXTR甲基化和mRNA表达的变化，以促进未来的新疗法发展。总而言之，SOARS-B明确测试了催产素，这是ASD核心社会症状的极为有希望的生物学治疗。 公共卫生相关性：公共卫生相关性这项研究与公共卫生和NIH任务有关，因为它严格测试了持续的催产素治疗是否减少了自闭症谱系障碍的核心社会交流症状（ASD）。每110名美国人中有一个ASD，通常在一生中持续存在，并且具有巨大的社会成本。我们还将确定影响催产素反应以预测催产素可能有所帮助的特征。