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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HD073984-02
Application #
8537789
Study Section
Special Emphasis Panel (ZHD1-DRG-H (54))
Program Officer
Kau, Alice S
Project Start
2012-09-04
Project End
2017-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
2
Fiscal Year
2013
Total Cost
$2,435,695
Indirect Cost
$349,275
Name
University of North Carolina Chapel Hill
Department
Psychiatry
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599