Intranasal Oxytocin in the Treatment of Autism

Autism is a developmental disorder characterized by abnormalities in speech and
communication, impaired social functioning, and repetitive behaviors and restricted
interests. A number of researchers have suggested that the neuropeptide oxytocin may be
implicated in the etiology of autism.

Given the likely possibility of dysregulated oxytocin in autism, the goal of this pilot
study is to investigate the long-term therapeutic effects of oxytocin in the treatment of
autism. One practical issue with oxytocin is that it does not exist in a pill form. Only the
intravenous form is available in the United States and this form may or may not pass the
blood-brain barrier. In addition, intravenous oxytocin is not practical for treatment
studies. One alternative is intranasal oxytocin; this form of administration is known to
pass the blood-brain barrier, and it is easy for participants to self-administer. Although
not available in the United States, we are in the process of receiving an Investigational
New Drug exemption for its use and can import it from Europe.

Thus, this pilot investigation will explore daily intranasal oxytocin in the treatment of
autism. Also, there are very few, if any, outcome measures to assess social functioning in
the "real world" in the context of clinical trials; yet, this is a major target for
intervention, especially in autism. Thus, a final goal of this study will be to explore the
use of Event Contingent Recording to index changes in social functioning and affect. Event
Contingent Recording is a methodology developed by personality/social psychologists, which
allows participants to report on symptoms, affect, and behavior close in time to experience.
In addition, to enabling more sensitive assessments, this methodology allows for the
assessment of more diverse (e.g., at home versus work) and more detailed measurements of
mood and behavior.

Finally, a portion of this study aims to perform gene expression profiling using fresh whole
blood to explore the molecular mechanisms underlying oxytocin therapy and oxytocin efficacy
in adults with high functioning autism or Asperger's syndrome. The systemic effects of
oxytocin therapy and the molecular basis for a positive treatment response to oxytocin are
not well understood. An understanding of the former may help predict those persons who may
suffer side-effects from treatment and the latter may help provide easily accessible
peripheral biomarkers that could predict treatment response.

Inclusion Criteria:

1. Male or female outpatients 18 to 60 years of age.

2. Meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text
Revision. The diagnosis will be confirmed with Autism Diagnostic Interview-Revised
and Autism Diagnostic Observation Schedule .

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

4. If already receiving stable nonpharmacologic educational, behavioral, and/or dietary
interventions, have continuous participation during the preceding 3 months prior to
Screening and will not electively initiate new or modify ongoing interventions for
the duration of the study.

5. Have normal physical examination and laboratory test results at Screening. If
abnormal, the finding(s) must be deemed clinically insignificant by the
Investigators.

6. The patient must be able to speak and understand English sufficiently to understand
the nature of the study and to allow for the completion of all study assessments.

7. Have a normal Intelligence Quotient (>70) supported by the Wechsler Abbreviated
Scales of Intelligence.

Exclusion Criteria:

1. Patients born prior to 35 weeks gestational age.

2. Patients with any primary psychiatric diagnosis other than autism at Screening: a
history of attention deficit hyperactivity disorder, bipolar disorder, psychosis,
posttraumatic stress disorder, schizophrenia, or major depressive disorder.

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 magnetic resonance imaging/structural lesion of the brain.

4. Pregnant female patients.

5. Patients with a medical condition that might interfere with the conduct of the study,
confound interpretation of the study results, or endanger their own well-being.
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 taking psychoactive medication(s) (e.g., stimulants, antidepressants,
antipsychotics, antiepileptics, anxiolytics, clonidine).

7. Patients who plan to initiate or change nonpharmacologic interventions during the
course of the study.

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

9. Patients who, in the Investigator's opinion, might not be suitable for the study.