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

描述(由申请人提供)：该申请建议创建ACE SOARS网络，并对患有ASD的儿童进行持续催产素治疗的关键临床试验，称为SOARS-B(研究ASD中的催产素以改善互惠的社会行为)。ACE Soars网络包括全国五个治疗中心，分别由Chris McDouger(MA)、Alex Kolevzon(NY)、Bryan King(西澳)、Lin Sikich(NC)和Jeremy Veenstra-Vander Weele(TN)领导；一个由Simon Gregory(杜克大学)运营的遗传中心；一个由Robert Hamer(北卡罗来纳大学)领导的数据中心；以及一个协调中心。ACE Soars网络的使命是开发安全的治疗方法，有意义地改善各种能力水平的自闭症谱系障碍(ASD)患者的功能，减少残疾，并确定预测谁将对何种治疗有反应的因素。ACE Soars网络以令人兴奋的新发现为基础，即催产素改善了典型发育和自闭症患者的社会行为，并建立在自闭症持续催产素治疗的试点研究结果的基础上，以开发一种优化的鼻内催产素形式，我们预计这种形式将被很好地耐受。我们假设催产素将增加ASD儿童的社会定向和社会奖励的价值，从而导致社会动机的增强和ASD核心社交和沟通症状的改善。ACE Soars Network将通过进行Soars-B严格验证这一假设，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用于改善3-17岁自闭症儿童的对等社会行为。我们将招募至少142名功能低下的参与者(严重的语言障碍和智力残疾的非语言智商为70)和至少142名高功能的参与者(流利的短语语言和非语言智商70)。在完成双盲治疗后，每个参与者都将接受为期六个月的开放标签催产素治疗，以更全面地评估更长时间治疗可能出现的安全性和功能益处。我们将确定优先影响催产素反应的临床特征(如年龄或语言流利性)和生物学因素(如催产素受体基因-OXTR的甲基化水平)。我们还将描述在催产素或安慰剂治疗后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，以促进未来新治疗的发展。总而言之，Soars-B将最终测试催产素，这是一种非常有希望的治疗自闭症核心社会症状的生物疗法。

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.