A Randomized, Controlled Trial of Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder

Study Overview
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Brief Summary
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This 3-year study is a trial of cognitive behavioral therapy (CBT), with or without oxytocin (OT) augmentation, in young adults with autism spectrum disorders. Participants will be randomly assigned to receive either a social skills-focused CBT intervention or a stress management/relaxation training CBT intervention. Participants will also be randomized to receive either a) intranasal oxytocin or b) a placebo drug, prior to the psychotherapy. The design of the study will enable examination of the efficacy of CBT for young adults with autism spectrum disorders. The design of the study will also allow examination of whether oxytocin enhances the efficacy of CBT. The investigators will perform functional (fMRI) and structural (MRI) imaging with all participants prior to treatment. This will enable examination of the relations between measures of brain function and structure, and improvements in target symptoms over the course of treatment. The aim is to discover whether there are neural characteristics that can identify which participants with autism spectrum disorders are most likely to respond to CBT interventions and/or oxytocin treatment.

Official Title
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A Randomized, Controlled Trial of Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder

Conditions
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Autism Spectrum Disorders

Intervention / Treatment
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* Drug: Oxytocin
* Behavioral: Social Skills focused CBT
* Behavioral: Stress management/relaxation training
* Drug: placebo drug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-40 Able to attend in person therapy sessions in Boston Male English-speaking Normal or corrected vision No history of known genetic disorder, significant motor developmental difficulties, prematurity or brain injury IQ > 90, as determined by the WASI Score above the cutoff on the Reciprocal Social Interactions and the Restricted, Repetitive, and Stereotyped Behaviors Domains on the ADI-R, meet criteria for PDD or autism on the ADOS, and/or meet DSM-IV criteria for Autism Spectrum Disorder according to clinician interview. Exclusion Criteria: Current use of certain endocrinologically relevant medications Current dependence on substances other than tobacco or caffeine History of serious medical illness, including neurological, endocrine, cardiac, respiratory, and metabolic diseases that are counter-indications to oxytocin Severe, current psychiatric disorder (ie, current mania, severe depression, psychosis, suicidality, severe aggression) Long QT, as determined by baseline EKG Current participation in other psychotherapy Additional exclusion criteria for MRI scan only: Participants who are MRI-ineligible will be enrolled in the clinical trial portion of the study, but will not undergo the MRI scan at MIT. Exclusion criteria for MRI are: Presence of metal implants or other metal in the body History of claustrophobia or inability to tolerate MRI

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Social Skills Focused CBT<br>Twelve weekly 60-minute sessions of social skills focused CBT | Behavioral: Social Skills focused CBT<br> <br> |
| Active Comparator: Stress Management/Relaxation Training<br>Twelve weekly 60-minute sessions of stress management training | Behavioral: Stress management/relaxation training<br> <br> |
| Experimental: Oxytocin<br>Intranasal administration of 24 IU of oxytocin | Drug: Oxytocin<br> <br> |
| Placebo Comparator: placebo drug<br>Intranasal placebo drug | Drug: placebo drug<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the Autism Diagnostic Observation Schedule (ADOS) | The ADOS is a semi-structured standardized assessment of communication and social interaction that is considered a gold-standard assessment of autism spectrum disorders. The study will use Module 4, designed for use with adolescents and adults. The primary endpoint(dependent measure) will be the change in a global impression of social engagement by a clinician who is an experienced ADOS administrator. This will be a rating on a 10-point scale and involve expert clinical judgement of the qualities and behaviors that are at the core of the social/communicative deficits. | At baseline and after 12 weeks of treatment | 
| Clinical Global Impression Scale (CGI) | Independent Evaluator rated measure of autism symptom severity and improvement | At baseline and every 4 week up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Social Responsiveness Scale (SRS) | 65-item rating scale that measures the severity of autism spectrum symptoms | At baseline and every 4 weeks up to 12 weeks | 
| Reading the Mind in the Eyes Test (RMET) | Computerized measure of social skills | At baseline and every 4 weeks up to 12 weeks | 
| Social Ball Tossing Task | Computerized measure of social skills | At baseline and every 4 weeks up to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autism spectrum disorder, social skills deficits, cognitive behavioral therapy, oxytocin, young adult