Oxytocin and Social Cognitive Skills Groups

NCT02918864 | Completed Phase 2 Results DMC

• 1 other identifier: 14062403
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Autism Spectrum Disorder

Keywords

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

Outcome Measures

Primary Outcomes (12)

• Change From Baseline in Social Behavior Impairment (SBI) Composite

  The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group\*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement.

  Baseline and Week 12 (Endpoint)

• Rate of Change From Baseline in Social Behavior Impairment (SBI) Composite

  The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group\*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement.

  Baseline and Week 12 (Endpoint)

• Change From Baseline in Social Behavior Impairment (SBI) Composite

  The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group\*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement.

  Baseline and Week 16 (1-month follow-up)

• Rate of Change From Baseline in Social Behavior Impairment (SBI) Composite

  The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group\*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement.

  Baseline and Week 16 (1-month follow-up)

• Change From Baseline in Social Behavior Impairment (SBI) Composite

  The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group\*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement.

  Baseline and Week 24 (3-month follow-up)

• Rate of Change From Baseline in Social Behavior Impairment (SBI) Composite

  The change from baseline in SBI is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group\*time interaction. SBI is a composite score based on Soorya et al. (2015) which identified measures that comprise this metric. Scores from the Children's Communication Checklist-2 (CCC-2) Social Relations and Nonverbal Communication subscales and the Griffith Empathy Measure (GEM) were standardized as z-scores using the sample means and standard deviations at baseline. CCC-2 subscale scores and reversed GEM total scores were used so higher z-scores reflect more impairment across measures. The SBI outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SBI z-score equals 0; higher individual scores indicate relatively more impairment in social behavior skills. Larger, negative slopes represent improvement.

  Baseline and Week 24 (3-month follow-up)

• Change From Baseline in Social Cognition (SC) Composite

  The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group\*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement.

  Baseline and Week 12 (Endpoint)

• Rate of Change From Baseline in Social Cognition (SC) Composite

  The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group\*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement.

  Baseline and Week 12 (Endpoint)

• Change From Baseline in Social Cognition (SC) Composite

  The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group\*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement.

  Baseline and Week 16 (1-month follow-up)

• Rate of Change From Baseline in Social Cognition (SC) Composite

  The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group\*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement.

  Baseline and Week 16 (1-month follow-up)

• Change From Baseline in Social Cognition (SC) Composite

  The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group\*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement.

  Baseline and Week 24 (3-month follow-up)

• Rate of Change From Baseline in Social Cognition (SC) Composite

  The change from baseline in SC is represented by the slope of each group. The primary outcome is the difference between groups in this rate of change or the group\*time interaction. SC is a composite score, including the Reading the Mind in the Eyes Test (RMET) and the Diagnostic Analysis of Nonverbal Accuracy-2 (DANVA2), based on Soorya et al. (2015). RMET has 28 items rated correct/incorrect (total 0-28). DANVA2 contains 4 sets of 24 items rated correct/incorrect (total 0-96). Percent correct was calculated for each measure given the difference in denominators and to allow for administrative omissions. Percentages were standardized as z-scores using the sample means and standard deviations at baseline. The SC outcome was subsequently derived by averaging the z-scores. At baseline, the sample average SC z-score equals 0; higher individual scores reflect stronger skills on social cognitive tasks compared to lower scores. Larger, positive slopes indicate skill improvement.

  Baseline and Week 24 (3-month follow-up)

Secondary Outcomes (15)

• Number of Responder and Non-responder Participants Based on CGI-I Scores at Week 12 (Endpoint)

  Week 12 (Endpoint)

• Number of Responder and Non-responder Participants Based on CGI-I Scores at Week 16 (1-month Follow-up)

  Week 16 (1-month follow-up)

• Number of Responder and Non-responder Participants Based on CGI-I Scores at Week 24 (3-month Follow-up)

  Week 24 (3-month follow-up)

• Change From Baseline in Social Functioning (SRS-2)

  Baseline and Week 12 (Endpoint)

• Rate of Change From Baseline in Social Functioning (SRS-2)

  Baseline and Week 12 (Endpoint)

Study Arms (2)

ION-ASD

EXPERIMENTAL

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; Behavioral: Social Cognitive Skills Training

Facilitated Play

ACTIVE COMPARATOR

The active comparison condition is a facilitated play therapy group.

Behavioral: Facilitated Play Therapy

Interventions

Oxytocin DRUG

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.

Also known as: Syntocinon

ION-ASD

Social Cognitive Skills Training BEHAVIORAL

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.

Also known as: NETT

ION-ASD

Facilitated Play Therapy BEHAVIORAL

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.

Facilitated Play

Eligibility Criteria

• Age: 8 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female outpatients, 8-11 years of age inclusive
• Meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) 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-5 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 intelligence quotient (IQ) ≥ 80 (both subtests of the Wechsler Intelligence Scale for Children-V (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.

You may not qualify if:

• 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 oxytocin (OXT) or have taken intranasal oxytocin (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
• Alanine transaminase (ALT) or aspartate transaminase (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

Sponsors & Collaborators

• Rush University Medical Center: lead
• University of Illinois at Chicago: collaborator
• University of Chicago: collaborator
• Northwestern University: collaborator
• Eotvos Lorand University: collaborator

Study Sites (1)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Related Publications (1)

• Soorya LV, Siper PM, Beck T, Soffes S, Halpern D, Gorenstein M, Kolevzon A, Buxbaum J, Wang AT. Randomized comparative trial of a social cognitive skills group for children with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2015 Mar;54(3):208-216.e1. doi: 10.1016/j.jaac.2014.12.005. Epub 2014 Dec 20.

  PMID: 25721186 BACKGROUND

MeSH Terms

Conditions

Autism Spectrum Disorder; Social Skills; Nonverbal Communication

Interventions

Oxytocin

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Social Behavior; Behavior; Communication

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Enrollment was slowed down during COVID-19 shut down resulting in the study being under-powered and some groups receiving modified protocols. Apriori secondary analyses of maintenance effects resulted in multiple comparisons tests (i.e., at week 16 and 24) which were not corrected to balance type I/type II errors. Additionally, social cognitive stimuli were not counterbalanced; thus, it's unclear whether social cognitive improvements across groups reflect learning or practice effects.

Results Point of Contact

• Title: Dr. Latha Valluripalli Soorya
• Organization: Rush University Medical Center

latha_soorya@rush.edu

(312) 942-6238

Study Officials

• Latha Soorya, PhD, BCBA

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry

Study Record Dates

• First Submitted: September 9, 2016
• First Posted: September 29, 2016
• Study Start: June 15, 2016
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: April 5, 2024
• Results First Posted: April 5, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)