Oxytocin and Social Cognitive Skills Groups

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.

Inclusion Criteria

1. Male or female outpatients, 8-11 years of age inclusive

2. 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.

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 IQ ≥ 80 (both subtests of the 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 OXT or have taken 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. ALT/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. BUN levels of > 100 mmol/L

7. Creatinine levels of > 100 µmol/L

8. Osmolality levels of > 330 mmol/kg