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

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.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorders
• Intervention / Treatment: Drug: Oxytocin; Behavioral: Social Skills focused CBT; Behavioral: Stress management/relaxation training; Drug: placebo drug

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Cambridge, Massachusetts, United States, 02139
      • Massachusetts Institute of Technology Martinos Imaging Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-Control Behavior Scale (SCBS)	Self-report questionnaire of coping and problem-solving skills	At baseline and every 4 weeks up to 12 weeks
Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)	Self-report questionnaire of psychosocial functioning	At baseline and every 4 weeks up to 12 weeks
Social Phobia and Anxiety Inventory (SPAI)	Self-report questionnaire of social anxiety	At baseline and every 4 weeks up to 12 weeks
Social Adjustment Scale (SAS)	Self-report and parent-rated measure of psychosocial functioning	At baseline and every 4 weeks up to 12 weeks
Vineland Adaptive Behavior Scales, 2nd Edition	Measure of adaptive and functional behaviors	At baseline and every 4 weeks up to 12 weeks
Beck Depression Inventory (BDI)	Self-report questionnaire of depression symptoms	At baseline and every 4 weeks up to 12 weeks
Global Assessment of Functioning (GAF)	Overall rating of impairment	At baseline and every 4 weeks up to 12 weeks
Safety Monitoring Uniform Report Form	Assessment of adverse effects associated with oxytocin or placebo	At baseline and every 4 weeks up to 12 weeks
Autism Diagnostic Interview-Revised (ADI-R)	Parent-report, clinician-administered assessment of autism spectrum disorder symptoms in their child	Baseline
Structured Clinical Interview for DSM-IV (SCID)	A semistructured, clinician-administered assessment that assesses the presence of major psychiatric disorders. It is administered to the participant and to a parent about the participant.	Baseline
Wechsler Intelligence Scales (WASI and WAIS-III)	Measures of current intellectual functioning. Will be used to assess inclusion/exclusion criteria.	Baseline
Care Utilization	Assessment of any treatments (including medications, naturopathic treatments, speech or occupational therapy, hospitalizations, and intensive day programs) received over the past month.	At baseline and every 4 weeks up to 12 weeks
Service Evaluation Questionnaire	Self-report questionnaire about the participant's satisfaction with the psychosocial treatment they received.	After 12 weeks of treatment
Participant Adherence to the Intervention	Information will be collected about a) the number of sessions attended by each participant; b) completion of homework assignments; and c) participation in the treatment sessions, using a 0-5 scale	after 12 weeks of treatment
Expectancy Rating Questionnaire	Brief, self-report questionnaire about the participant's expectations of and belief in the social skills or stress management/relaxation interventions presented in the first session.	at week 1 of treatment
Adaptive Behavioral Assessment Scale-3rd edition	self-report measure of adaptive functioning	at weeks, 1, 4, 8, and 12

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Massachusetts Institute of Technology
• Investigators: Principal Investigator: John Gabrieli, PhD, Massachusetts General Hospital/MIT; Principal Investigator: Aude Henin, PhD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: July 29, 2013
• First Submitted That Met QC Criteria: July 31, 2013
• First Posted (Estimate): August 2, 2013

Study Record Updates

• Last Update Posted (Actual): January 27, 2020
• Last Update Submitted That Met QC Criteria: January 23, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: young adult; oxytocin; autism spectrum disorder; cognitive behavioral therapy; social skills deficits
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Neurodevelopmental Disorders; Disease; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: W81XWH-12-1-0543; Clinical Trial Award (Other Grant/Funding Number: Department of Defense-Autism Research Program)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No