Clinical trial NCT02918864: Oxytocin and Social Cognitive Skills Groups
Official title: Integrated Oxytocin and Nonverbal, Emotion Recognition, and Theory of Mind Training for Children With Autism Spectrum Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Rush University Medical Center
Sponsor class: OTHER
Collaborators: name: University of Illinois at Chicago
name: University of Chicago
name: Northwestern University
name: Eotvos Lorand University
First posted: 2016-09-29
Enrollment: 40
Sex: ALL
Minimum age (years): 8
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Detailed description: 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 (OXT), 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.

Eligibility criteria: Inclusion Criteria

1. Male or female outpatients, 8-11 years of age inclusive
2. 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.
3. Mean score of 9 or less on mentalizing items of Strange Stories Test (Highest possible score = 12, items 21-25, 27).
4. Have a Clinician's Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Baseline.
5. Verbal and performance scale intelligence quotient (IQ) ≥ 80 (both subtests of the Wechsler Intelligence Scale for Children-V (WISC-V) ≥ 70).
6. 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.
7. 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.
8. 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.
9. Ability to speak and understand English sufficiently to allow for the completion of all study assessments.
10. Ability to obtain written assent from the participant as well as written informed consent from their parent(s)/legal guardian.

Exclusion Criteria

1. Patients born prior to 35 weeks gestational age.
2. Patients with a primary psychiatric diagnosis other than ASD.
3. 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.
4. 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.
5. Patients with evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease.
6. 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.
7. Patients who are currently taking oxytocin (OXT) or have taken intranasal oxytocin (IN-OXT) in the past with no response.
8. Patients who have an Aberrant Behavior Checklist (ABC) Irritability subscale score \> 19 at screening
9. Patients with sensitivity to OXT or any components of its formulation.
10. Patients unable to tolerate venipuncture procedures for blood sampling.
11. Patients in foster care for whom the state is defined as a legal guardian.
12. If they have an arrhythmia present on ECG, that upon consultation with a cardiologist, is deemed to be clinically significant.
13. Patients with any of the following clinical lab results

    1. Alanine transaminase (ALT) or aspartate transaminase (AST) levels of ≥ 5 times the upper limit of normal, or if clinical jaundice occurs
    2. Sodium levels of \> 152 mmol/L or \< 128 mmol/L
    3. Potassium levels of \> 6 mmol/L in a non-hemolyzed sample
    4. Glucose levels of \> 11 mmol/L or \< 2.8 mmol/L
    5. Hemoglobin levels of \< 100 g/L
    6. Blood urea nitrogen (BUN) levels of \> 100 mmol/L
    7. Creatinine levels of \> 100 µmol/L
    8. Osmolality levels of \> 330 mmol/kg

Primary outcomes:
measure: Change From Baseline in Social Behavior Impairment (SBI) Composite
timeFrame: Baseline and Week 12 (Endpoint)
measure: Rate of Change From Baseline in Social Behavior Impairment (SBI) Composite
timeFrame: Baseline and Week 12 (Endpoint)
measure: Change From Baseline in Social Behavior Impairment (SBI) Composite
timeFrame: Baseline and Week 16 (1-month follow-up)
measure: Rate of Change From Baseline in Social Behavior Impairment (SBI) Composite
timeFrame: Baseline and Week 16 (1-month follow-up)
measure: Change From Baseline in Social Behavior Impairment (SBI) Composite
timeFrame: Baseline and Week 24 (3-month follow-up)
measure: Rate of Change From Baseline in Social Behavior Impairment (SBI) Composite
timeFrame: Baseline and Week 24 (3-month follow-up)
measure: Change From Baseline in Social Cognition (SC) Composite
timeFrame: Baseline and Week 12 (Endpoint)
measure: Rate of Change From Baseline in Social Cognition (SC) Composite
timeFrame: Baseline and Week 12 (Endpoint)
measure: Change From Baseline in Social Cognition (SC) Composite
timeFrame: Baseline and Week 16 (1-month follow-up)
measure: Rate of Change From Baseline in Social Cognition (SC) Composite
timeFrame: Baseline and Week 16 (1-month follow-up)
measure: Change From Baseline in Social Cognition (SC) Composite
timeFrame: Baseline and Week 24 (3-month follow-up)
measure: Rate of Change From Baseline in Social Cognition (SC) Composite
timeFrame: Baseline and Week 24 (3-month follow-up)
Secondary outcomes:
measure: Number of Responder and Non-responder Participants Based on CGI-I Scores at Week 12 (Endpoint)
timeFrame: Week 12 (Endpoint)
measure: Number of Responder and Non-responder Participants Based on CGI-I Scores at Week 16 (1-month Follow-up)
timeFrame: Week 16 (1-month follow-up)
measure: Number of Responder and Non-responder Participants Based on CGI-I Scores at Week 24 (3-month Follow-up)
timeFrame: Week 24 (3-month follow-up)
measure: Change From Baseline in Social Functioning (SRS-2)
timeFrame: Baseline and Week 12 (Endpoint)
measure: Rate of Change From Baseline in Social Functioning (SRS-2)
timeFrame: Baseline and Week 12 (Endpoint)
measure: Change From Baseline in Social Functioning (SRS-2)
timeFrame: Baseline and Week 16 (1-month follow-up)
measure: Rate of Change From Baseline in Social Functioning (SRS-2)
timeFrame: Baseline and Week 16 (1-month follow-up)
measure: Change From Baseline in Social Functioning (SRS-2)
timeFrame: Baseline and Week 24 (3-month follow-up)
measure: Rate of Change From Baseline in Social Functioning (SRS-2)
timeFrame: Baseline and Week 24 (3-month follow-up)
measure: Change From Baseline in Quality of Life (CGSQ)
timeFrame: Baseline and Week 12 (Endpoint)
measure: Rate of Change From Baseline in Quality of Life (CGSQ)
timeFrame: Baseline and Week 12 (Endpoint)
measure: Change From Baseline in Quality of Life (CGSQ)
timeFrame: Baseline and Week 16 (1-month follow-up)
measure: Rate of Change From Baseline in Quality of Life (CGSQ)
timeFrame: Baseline and Week 16 (1-month follow-up)
measure: Change From Baseline in Quality of Life (CGSQ)
timeFrame: Baseline and Week 24 (3-month follow-up)
measure: Rate of Change From Baseline in Quality of Life (CGSQ)
timeFrame: Baseline and Week 24 (3-month follow-up)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
Study officials:
affiliation: Rush University Medical Center
name: Latha Soorya, PhD, BCBA
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.