Rationale, design, and methods of the Autism Centers of Excellence (ACE) network Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B)

Abstract

To describe the rationale, design, and methods of the Autism Centers of Excellence (ACE) network Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B). Method: This phase 2 clinical trial was designed to evaluate the use of intranasal oxytocin treatment to improve social difficulties in individuals with autism spectrum disorder (ASD). In total, 290 participants ages 3 to 17 years with a DSM-5 diagnosis of ASD were enrolled to receive 24 weeks of treatment with either oxytocin or a matched placebo at one of seven collaborating sites. Participants were subsequently treated with open-label oxytocin for 24 additional weeks. Post-treatment assessments were done approximately 4 weeks after treatment discontinuation. Plasma oxytocin and oxytocin receptor gene (OXTR) methylation level were measured at baseline, and week 8, 24 and 36 to explore potential relationships between these biomarkers and treatment response. Results: This report describes the rationale, design, and methods of the SOARS-B clinical trial. Conclusions: There is a tremendous unmet need for safe and effective pharmacological treatment options that target the core symptoms of ASD. Several studies support the hypothesis that intranasal oxytocin could improve social orienting and the salience of social rewards in ASD, thereby enhancing reciprocal social behaviors. However, due to conflicting results from a number of pilot studies on the prosocial effects of exogenous oxytocin, this hypothesis remains controversial and inconclusive. SOARS-B is the best powered study to date to address this hypothesis and promises to improve our understanding of the safety and efficacy of intranasal oxytocin in the treatment of social deficits in children with ASD.

Genetic and epigenetic signatures associated with plasma oxytocin levels in children and adolescents with autism spectrum disorder

“…A full description of the SOARS-B clinical trial and study population has been previously reported 18, 50 . Briefly, 355 children and adolescents were screened for study inclusion, with 290 individuals with ASD enrolled and randomized 1:1 to intranasal placebo or oxytocin spray in a multi-site clinical trial.…”

“…All batches were background-corrected and quantile-normalized together using limma’s neqc function. Samples were excluded from analyses if they were flagged as a sample swap in analysis of each omics dataset or if they came from an individual that had an underlying genetic condition, as defined in the SOARS-B study 18, 50 . Probes were excluded if they displayed poor mapping quality or were not detected across all samples.…”

“…All analyses were performed on plasma OT measurements obtained at screen or baseline study visits (i.e., pre-treatment), either as the dependent variable of interest or as the independent variable of interest (in transcriptome and methylome analyses executed using limma). We adjusted for a consistent set of covariates across all modalities that included functional strata as defined in the SOARS-B study 18, 50 , age at sample, sex, 3 principal components reflecting genetic ancestry, and oxytocin measurement batch (which was correlated with participants’ study site). Modality-specific covariates were adjusted for as necessary and included gene-expression assay batch, OXTR assay plate, and a series of covariates to adjust for cell-type proportions and assay position within the methylome dataset.…”

An Update on Psychopharmacological Treatment of Autism Spectrum Disorder

“…Nonetheless, as illustrated by a recent meta-analysis, there does seem to be overall beneficial effects of OXT on social symptoms of ASD, although this review included both children and adults [90]. There is also some promising research looking at the role of OXT in combination with other treatment modalities including behavior therapy and probiotics, with clinical trials in this area ongoing [91,92]. It is also likely that the effects of OXT in ASD are modulated by age, gender, and possibly genetic factors [77,79,90].…”

Priming the Pathway: Combining Oxytocin and Behavioral Intervention to Improve Outcomes in Autism Spectrum Disorder

“…We also note that a large-scale multi-site trial of the behavioral effects of oxytocin versus placebo is underway by the Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors (SOARS-B; clinical trial identifier NCT01944046). One paper describing the rationale and methods for the trial has been published [93].…”