Intranasal Oxytocin for the Treatment of Children and Adolescents With Autism Spectrum Disorders (ASD)

Extensive data has been accumulated to suggest that central release of oxytocin is important
for social cognition and function, as well as likely involved in anxiety modulation and
repetitive behaviors. The Principal Investigator and Co-Principal Investigator of this study
have previously documented: 1) an association between ASD and a single nuclear polymorphism
of the oxytocin receptor gene, 2) ability to measure oxytocin levels in the blood by enzyme
immunoassay and 3) preliminary data to support safety and efficacy of intranasal oxytocin in
the treatment of social deficits and repetitive behaviors in adults with autism. A
medication treatment targeting the core deficits of ASD in childhood is highly valuable
because it could influence the developmental trajectory and make further psychosocial
interventions possible. In this context, we propose a randomized placebo controlled trial of
intranasal oxytocin in children and adolescents with ASD.

Inclusion Criteria

1. Male or female outpatients, 10-17 years of age inclusive.

2. Meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Diagnostic
and Statistical Manual (DSM-IV) criteria will be established by a clinician with
expertise with individuals with ASD. Best estimate Diagnosis will be reached using
DSM-IV criteria, the Autism Diagnostic Observation Schedule (ADOS-2) and the Autism
Diagnostic Interview (ADI-R).

3. Have a Clinician's Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at
Screening.

4. Verbal and performance scale Intelligence Quotient (IQ) ≥ 70 (both subtests of the
Wechsler Abbreviated Scale of Intelligence (WASI-I or WASI-II ≥ 70).

5. If already receiving stable concomitant medications affecting behavior, have
continuous participation for 1 month prior to Screening (with the exception of
fluoxetine, where a period of 6 weeks is needed), and not electively initiate new or
modify ongoing medications for the duration of the study.

6. 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.

7. 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.

8. Ability to speak and understand English sufficiently to allow for the completion of
all study assessments.

9. Ability to obtain written informed consent from the participant, if developmentally
appropriate. If a participant does not have the capacity to consent, ability to
obtain assent (if developmentally appropriate), 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: HIV, Hepatitis B virus, Hepatitis C
virus, 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 or have taken intranasal oxytocin in the
past with no response.

8. Patients with a sensitivity to oxytocin or any components of its formulation.

9. Patients unable to tolerate venipuncture procedures for blood sampling.

10. Patients in foster care for whom the province/state is defined as a legal guardian