Intranasal Oxytocin in the Treatment of Autism

• Clinical Global Impressions Scale (CGI) [ Time Frame: Baseline visit, week 2, 4, and 6 visits ] [ Designated as safety issue: No ]
• Repetitive Behavior Scale (RBS) [ Time Frame: Baseline visit, week 2, 4, and 6 visits ] [ Designated as safety issue: No ]
• Diagnostic Analysis of Nonverbal Accuracy, Adult Paralanguage Test (DANVA2-AP) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
• Diagnostic Analysis of Nonverbal Accuracy, Adult Paralanguage Test (DANVA2-AP) [ Time Frame: 6 week visit ] [ Designated as safety issue: No ]

• Clinical Global Impressions Scale (CGI) [ Time Frame: Baseline visit, week 2, 4, and 6 visits ]
• Repetitive Behavior Scale (RBS) [ Time Frame: Baseline visit, week 2, 4, and 6 visits ]
• Diagnostic Analysis of Nonverbal Accuracy, Adult Paralanguage Test (DANVA2-AP) [ Time Frame: Baseline and week 6 visits ]
• Event Contingent Reporting [ Time Frame: Baseline, week 2 and 6 visits ]

• Yale-Brown Obsessive-Compulsive Scale (YBOCS) [ Time Frame: Baseline visit, week 2, 4, and 6 visits ] [ Designated as safety issue: No ]
• Social Responsivity Scale (SRS) [ Time Frame: Baseline visit, week 2, 4, and 6 visits ] [ Designated as safety issue: No ]

• Yale-Brown Obsessive-Compulsive Scale (YBOCS) [ Time Frame: Baseline visit, week 2, 4, and 6 visits ]
• Social Responsivity Scale (SRS) [ Time Frame: Baseline visit, week 2, 4, and 6 visits ]

The purpose of this study is to learn whether or not the drug called Oxytocin is helpful in improving mood and social functioning in adults with autism.

Definition: Extended description of the protocol, including information not already contained in other fields, such as comparison(s) studied.

Autism is a developmental disorder characterized by abnormalities in speech and communication, impaired social functioning, and repetitive behaviors and restricted interests (American Psychiatric Association, 2000). A number of researchers have suggested that the neuropeptide oxytocin may be implicated in the etiology of autism (Hollander et al., 2003; Insel et al., 1999; Lim et al., 2005; McCarthy & Altemus, 1997; Modahl et al., 1992; Waterhouse et al., 1996).

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 US and this form may or may not pass the blood-brain barrier. In addition, IV 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 US, we are in the process of receiving an IND 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 (ECR) to index changes in social functioning and affect. ECR 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.

• Drug: Oxytocin
  Intranasal Oxytocin
• Drug: Placebo Comparator
  Placebo Comparator

• Experimental: Intranasal Oxytocin
  Intervention: Drug: Oxytocin
• Placebo Comparator: Placebo
  Drug
  Intervention: Drug: Placebo Comparator

Inclusion Criteria:

1. Male or female outpatients 18 to 60 years of age.
2. Meet DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision). The diagnosis will be confirmed with Autism Diagnostic Interview-Revised (ADI-R) and ADOS .
3. Have a Clinician's Global Impression-Severity (CGI-S) 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 IQ (>70) supported by the Wechsler Abbreviated Scales of Intelligence (WASI).

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 ADHD, 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 MRI/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.