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

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01914939

Collaborator

Massachusetts Institute of Technology (Other)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Autism Spectrum Disorders	Drug: Oxytocin Behavioral: Social Skills focused CBT Behavioral: Stress management/relaxation training Drug: placebo drug	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

92 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2014

Actual Primary Completion Date :

Nov 1, 2017

Actual Study Completion Date :

Nov 1, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Changes in the Autism Diagnostic Observation Schedule (ADOS) [At baseline and after 12 weeks of treatment]
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.
Clinical Global Impression Scale (CGI) [At baseline and every 4 week up to 12 weeks]
Independent Evaluator rated measure of autism symptom severity and improvement

Secondary Outcome Measures

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

Other Outcome Measures

Self-Control Behavior Scale (SCBS) [At baseline and every 4 weeks up to 12 weeks]
Self-report questionnaire of coping and problem-solving skills
Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) [At baseline and every 4 weeks up to 12 weeks]
Self-report questionnaire of psychosocial functioning
Social Phobia and Anxiety Inventory (SPAI) [At baseline and every 4 weeks up to 12 weeks]
Self-report questionnaire of social anxiety
Social Adjustment Scale (SAS) [At baseline and every 4 weeks up to 12 weeks]
Self-report and parent-rated measure of psychosocial functioning
Vineland Adaptive Behavior Scales, 2nd Edition [At baseline and every 4 weeks up to 12 weeks]
Measure of adaptive and functional behaviors
Beck Depression Inventory (BDI) [At baseline and every 4 weeks up to 12 weeks]
Self-report questionnaire of depression symptoms
Global Assessment of Functioning (GAF) [At baseline and every 4 weeks up to 12 weeks]
Overall rating of impairment
Safety Monitoring Uniform Report Form [At baseline and every 4 weeks up to 12 weeks]
Assessment of adverse effects associated with oxytocin or placebo
Autism Diagnostic Interview-Revised (ADI-R) [Baseline]
Parent-report, clinician-administered assessment of autism spectrum disorder symptoms in their child
Structured Clinical Interview for DSM-IV (SCID) [Baseline]
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.
Wechsler Intelligence Scales (WASI and WAIS-III) [Baseline]
Measures of current intellectual functioning. Will be used to assess inclusion/exclusion criteria.
Care Utilization [At baseline and every 4 weeks up to 12 weeks]
Assessment of any treatments (including medications, naturopathic treatments, speech or occupational therapy, hospitalizations, and intensive day programs) received over the past month.
Service Evaluation Questionnaire [After 12 weeks of treatment]
Self-report questionnaire about the participant's satisfaction with the psychosocial treatment they received.
Participant Adherence to the Intervention [after 12 weeks of treatment]
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
Expectancy Rating Questionnaire [at week 1 of treatment]
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.
Adaptive Behavioral Assessment Scale-3rd edition [at weeks, 1, 4, 8, and 12]
self-report measure of adaptive functioning

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Massachusetts Institute of Technology Martinos Imaging Center	Cambridge	Massachusetts	United States	02139