Clinical trial of modulatory effects of oxytocin treatment on higher-order social cognition in autism spectrum disorder: a randomized, placebo-controlled, double-blind and crossover trial.

Sören Krach,Frieder M Paulus,Philipp Kanske,Tania Singer,Katrin Preckel

doi:10.1186/s12888-016-1036-x

Abstract

BackgroundAutism spectrum disorders are neurodevelopmental conditions with severe impairments in social communication and interaction. Pioneering research suggests that oxytocin can improve motivation, cognition and attention to social cues in patients with autism spectrum disorder. The aim of this clinical trial is to characterize basic mechanisms of action of acute oxytocin treatment on neural levels and to relate these to changes in different levels of socio-affective and -cognitive functioning.MethodsThis clinical study is a randomized, double-blind, cross-over, placebo-controlled, multicenter functional magnetic resonance imaging study with two arms. A sample of 102 male autism spectrum disorder patients, diagnosed with Infantile Autistic Disorder (F84.0 according to ICD-10), Asperger Syndrome (F84.5 according to ICD-10), or Atypical Autism (F84.1 according to ICD-10) will be recruited and will receive oxytocin and placebo nasal spray on two different days. Autism spectrum disorder patients will be randomized to determine who receives oxytocin on the first and who on the second visit. Healthy control participants will be recruited and case-control matched to the autism spectrum disorder patients. The primary outcome will be neural network activity, measured with functional magnetic resonance imaging while participants perform socio-affective and -cognitive tasks. Behavioral markers such as theory of mind accuracy ratings and response times will be assessed as secondary outcomes in addition to physiological measures such as skin conductance. Trait measures for alexithymia, interpersonal reactivity, and social anxiety will also be evaluated. Additionally, we will analyze the effect of oxytocin receptor gene variants and how these potentially influence the primary and secondary outcome measures. Functional magnetic resonance imaging assessments will take place at two time points which will be scheduled at least two weeks apart to ensure a sufficient wash-out time after oxytocin treatment. The study has been approved by an ethical review board and the competent authority.DiscussionRevealing the mechanisms of acute oxytocin administration, especially on the socio-affective and -cognitive domains at hand, will be a further step towards novel therapeutic interventions regarding autism.Trial registrationGerman Clinical Trial Register DRKS00010053. The trial was registered on the 8th of April 2016

Highlights

Autism spectrum disorders are neurodevelopmental conditions with severe impairments in social communication and interaction
Design and settings This study description is in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines that are published for the evaluation of randomized controlled trials [36]
Eligibility Autism Spectrum Disorders (ASD) patients will be eligible participants if: 1) they are male, 2) they are aged between 19 and 40 years, 3) their mother tongue is German, 4) they have an intelligence quotient (IQ) above 70, 5) they have one of the following diagnoses: Infantile Autism, (F84.0 according to ICD-10), Asperger Syndrome (F84.5 according to ICD-10), or Atypical Autism (F84.1 according to ICD-10), 6) they have given written informed consent

Summary

Methods

Design and settings This study description is in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines that are published for the evaluation of randomized controlled trials [36]. Pulse and blood pressure will be measured before and after nasal spray administration, to monitor OXT’s potential side effects and inclusion/ exclusion criteria Physiological data, such as fixation patterns, pupil dilation, heart rate, respiration, and skin conductance patterns will be acquired during the fMRI assessments. Structural brain markers The structural measurements in this clinical trial will serve the comparison between ASD patients and HCs, not the comparison of the treatment groups (OXT vs PLC). Participants are carefully instructed and an explanation of what is meant by the Primary outcome Neural correlates of socio-affective and -cognitive tasks in ASD patients and HCs will be assessed after PLC and after OXT administration at two time points (cross-over design) using fMRI. All task-related main effects and interactions will be calculated for participant (ASD vs HC) and treatment (OXT vs PLC) groups.

Discussion

Background