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

描述（由申请人提供）：本申请提议建立ACE SOARS网络和一项持续催产素治疗ASD儿童的关键临床试验，称为SOARS- b （ASD中催产素改善互惠社会行为的研究）。ACE SOARS网络由全国五个治疗站点组成，由Chris McDougle (MA), Alex Kolevzon (NY), Bryan King (WA), Lin Sikich （NC）和Jeremy Veenstra-Vander Weele （TN）领导，由Simon Gregory （Duke）管理的遗传中心；由罗伯特·哈默（UNC）领导的数据中心；和一个协调中心。ACE SOARS网络的使命是开发安全的治疗方法，有效地改善各种能力水平的自闭症谱系障碍（ASD）患者的功能和减少残疾，并确定预测哪些人对哪种治疗有反应的因素。ACE SOARS网络建立在令人兴奋的新发现的基础上，即催产素增强了典型发育和ASD患者的社会行为，以及在ASD中持续治疗催产素的初步研究结果，从而开发出一种优化的鼻内催产素，我们预计这种催产素将具有良好的耐受性。我们假设催产素会增加ASD儿童的社会导向和社会奖励的价值，从而导致社会动机增强，改善ASD的核心社会和沟通症状。ACE SOARS网络将通过SOARS- b严格检验这一假设，这是一项大型（n=300）、随机双盲、安慰剂对照试验，持续（6个月）、灵活剂量的鼻内催产素治疗可改善3-17岁ASD儿童的互惠社会行为。我们将招募至少142名低功能（严重语言障碍和智力残疾，非语言智商< 70）和至少142名高功能（流利的短语演讲和非语言智商≥70）的参与者。在完成双盲治疗后，每位参与者将接受开放标签催产素治疗6个月，以更全面地评估长期治疗可能出现的安全性和功能益处。我们将确定临床特征（如年龄或语言流畅性）和生物因素（如催产素受体基因- OXTR的甲基化水平）优先影响催产素反应。我们还将描述催产素或安慰剂治疗后ASD中与催产素信号相关的OXTR甲基化和基因mRNA表达的变化，以促进未来新疗法的发展。总之，sox - b将明确测试催产素，这是一种非常有前途的ASD核心社会症状的生物治疗方法。

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.