Oxytocin and Social Cognitive Skills Groups

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the feasibility, safety, and preliminary efficacy of integrating targeted dosing of intranasal oxytocin with a social cognitive skills group therapy for school-aged children with autism spectrum disorder (ASD).

Detailed Description
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The study is a proof-of-concept, combination intervention designed to address individual treatment targets presumed to influence social learning in school-aged children with autism spectrum disorder (ASD). This proposal builds upon prior research on an empirically supported social cognitive skills training curriculum, NETT (Nonverbal communication, Emotion recognition, and Theory of mind Training). NETT is a cognitive-behavioral intervention (CBI) for nonverbal communication, emotion recognition, and theory of mind deficits in youth with ASD. In this two-phase, 3 year, single-blind, contact controlled study, school-aged children with ASD (n=60) will be randomized into a 12-session, parallel group design of Integrated Oxytocin and NETT (ION) or a control social group condition (facilitated play). The study aims to evaluate the safety, tolerability, and efficacy of integrating the neuropeptide, oxytocin (OT), with the social cognitive curriculum, as well as to identify targets of change and pre-treatment factors predictive of response to ION-ASD. Maintenance of treatment effects will also be assessed 1 month and 3 months post-treatment.

Official Title
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Integrated Oxytocin and Nonverbal, Emotion Recognition, and Theory of Mind Training for Children With Autism Spectrum Disorder

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Drug: Oxytocin
* Behavioral: Social Cognitive Skills Training
* Behavioral: Facilitated Play Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male or female outpatients, 8-11 years of age inclusive Meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition for Autism Spectrum Disorder. DSM-V criteria will be established by a clinician with expertise with individuals with ASD. Best estimate Diagnosis will be reached using DSM-V criteria, the Autism Diagnostic Observation Schedule (ADOS-2) and the Autism Diagnostic Interview (ADI-R), or Autism Screening Interview. Mean score of 9 or less on mentalizing items of Strange Stories Test (Highest possible score = 12, items 21-25, 27). Have a Clinician's Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Baseline. Verbal and performance scale IQ ≥ 80 (both subtests of the WISC-V ≥ 70). If already receiving stable concomitant medications, have continuous participation during the preceding 30 days prior to Screening, and not electively initiate new or modify ongoing medications for the duration of the study. For serotonergic agents, 6 months on a stable dose is required. If already receiving stable non-pharmacologic educational, behavioral, and/or dietary interventions, have continuous participation during the preceding 3 months prior to Screening, and not electively initiate new or modify ongoing interventions for the duration of the study. Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed not clinically significant by the Treating Clinician. Ability to speak and understand English sufficiently to allow for the completion of all study assessments. Ability to obtain written assent from the participant as well as written informed consent from their parent(s)/legal guardian. Exclusion Criteria Patients born prior to 35 weeks gestational age. Patients with a primary psychiatric diagnosis other than ASD. Patients with a medical history of neurological disease, including, but not limited to, epilepsy/seizure disorder (except simple febrile seizures), movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes, or known abnormal brain MRI/structural lesion. Pregnant female patients, sexually active female patients on hormonal birth control and sexually active females who do not use at least two types of non-hormonal birth control. Patients with evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease. Patients with one or more of the following: hemophilia (bleeding problems, recent nose and brain injuries), abnormal blood pressure (hypotension or hypertension), drug abuse, immunity disorder or severe depression. Patients who are currently taking OXT or have taken IN-OXT in the past with no response. Patients who have an Aberrant Behavior Checklist (ABC) Irritability subscale score > 19 at screening Patients with sensitivity to OXT or any components of its formulation. Patients unable to tolerate venipuncture procedures for blood sampling. Patients in foster care for whom the state is defined as a legal guardian. If they have an arrhythmia present on ECG, that upon consultation with a cardiologist, is deemed to be clinically significant. Patients with any of the following clinical lab results ALT/AST levels of ≥ 5 times the upper limit of normal, or if clinical jaundice occurs Sodium levels of > 152 mmol/L or < 128 mmol/L Potassium levels of > 6 mmol/L in a non-hemolyzed sample Glucose levels of > 11 mmol/L or < 2.8 mmol/L Hemoglobin levels of < 100 g/L BUN levels of > 100 mmol/L Creatinine levels of > 100 µmol/L Osmolality levels of > 330 mmol/kg

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ION-ASD<br>ION-ASD integrates targeted dosing of intranasal oxytocin and social cognitive skills group training curriculum, Seaver-NETT (Nonverbal communication, Emotion recognition, Theory of mind Training). | Drug: Oxytocin<br>* This is an integrated pharmacological-behavioral intervention targeting social cognitive skills for school-aged children with ASD. Four doses of intranasal oxytocin (24 IUs/dose) will be delivered each week before weekly homework and group therapy sessions.<br>Behavioral: Social Cognitive Skills Training<br>* Social cognitive skills training utilize cognitive behavioral strategies such as problem identification, affective education, performance feedback, and weekly homework activities to target impairments in nonverbal synchrony, emotional expression, and interpretation of intent. The NETT curriculum is manualized and anchored in CBI strategies, such as problem identification, affective education, performance feedback, and weekly homework activities. Parent education sessions run concurrently with child groups to help facilitate generalization.<br>|
| Active Comparator: Facilitated Play<br>The active comparison condition is a facilitated play therapy group. | Behavioral: Facilitated Play Therapy<br>* The facilitated play therapy group is a manualized treatment designed to tailor play to the interests and abilities of group members. Therapists use general therapeutics strategies such as reflective functioning statements to foster communication with therapists as well as between peers. Standard educational practices for children with ASD such as visual supports, schedules, and short-directed statements are also used. The concurrent parent group is supportive in nature.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Social Behavior Composite | This domain will be measured by a composite score developed through a factor analysis of the following caregiver report measures: Children's Communication Checklist (CCC) and the Griffith Empathy Scale. | Week 12 (Endpoint) | 
| Change from Baseline in Social Behavior Composite | This domain will be measured by a composite score developed through a factor analysis of the following caregiver report measures: Children's Communication Checklist (CCC) and the Griffith Empathy Scale. | Week 16 (follow-up) | 
| Change from Baseline in Social Behavior Composite | This domain will be measured by a composite score developed through a factor analysis of the following caregiver report measures: Children's Communication Checklist (CCC) and the Griffith Empathy Scale. | Week 24 (follow-up) | 
| Change from Baseline in Social Cognition Composite | This domain will be measured by a composite score developed through a factor analysis of the following caregiver report measures: Reading Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2) | Week 12 (Endpoint) | 
| Change from Baseline in Social Cognition Composite | This domain will be measured by a composite score developed through a factor analysis of the following caregiver report measures: Reading Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2) | Week 16 (follow-up) | 
| Change from Baseline in Social Cognition Composite | This domain will be measured by a composite score developed through a factor analysis of the following caregiver report measures: Reading Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2) | Week 24 (follow-up) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Global Functioning | Global Functioning will be assessed using the Clinical Global Impressions-Improvement Scale. The CGI-I employs a seven point (1 = very much improved to 7 = very much worse) to determine the patient's improvement in response to treatment. | Week 12 (Endpoint) | 
| Change from Baseline in Global Functioning | Global Functioning will be assessed using the Clinical Global Impressions-Improvement Scale. The CGI-I employs a seven point (1 = very much improved to 7 = very much worse) to determine the patient's improvement in response to treatment. | Week 16 (follow-up) | 
| Change from Baseline in Global Functioning | Global Functioning will be assessed using the Clinical Global Impressions-Improvement Scale. The CGI-I employs a seven point (1 = very much improved to 7 = very much worse) to determine the patient's improvement in response to treatment. | Week 24 (follow-up) | 
| Change from Baseline in Social Functioning | Social Functioning will be assessed using the Social Responsiveness Scale | Week 12 (Endpoint) | 
| Change from Baseline in Social Functioning | Social Functioning will be assessed using the Social Responsiveness Scale | Week 16 (follow-up) | 
| Change from Baseline in Social Functioning | Social Functioning will be assessed using the Social Responsiveness Scale | Week 24 (follow-up) | 
| Change from Baseline in Quality of Life | Quality of Life will be assessed using the Caregiver Strain Questionnaire | Week 12 (Endpoint) | 
| Change from Baseline in Quality of Life | Quality of Life will be assessed using the Caregiver Strain Questionnaire | Week 16 (follow-up) | 
| Change from Baseline in Quality of Life | Quality of Life will be assessed using the Caregiver Strain Questionnaire | Week 24 (follow-up) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autism Spectrum Disorder, Oxytocin, Social Skills, Social cognitive skills, Cognitive Behavioral Intervention, Combination treatment, Syntocinon, NETT (Nonverbal communication, Emotion recognition, Theory of mind Training), emotion recognition, theory of mind