Individuals with Prader-Willi syndrome (PWS) have been found to have a deficit of oxytocin-producing neurons and decreased oxytocin receptor gene function, so the purpose of this study is to determine if oxytocin (OT) administration will improve some of the aspects of Prader-Willi syndrome that are particularly troublesome for children and their families (the insatiable appetite and social behaviors).

The research questions are:

1. Does intranasal oxytocin cause any side effects in children with PWS?
2. Does intranasal oxytocin administration alter appetite or behaviors in PWS?

This study is to investigate if intranasal oxytocin will improve hyperphagia, social skills, and behaviors in subjects with Prader-Willi syndrome. This will be a randomized placebo controlled pilot study. The primary outcome measure is to determine if intranasal administration of oxytocin will cause any adverse events in subjects with Prader-Willi syndrome. Secondarily, the investigators will also perform evaluations to determine if intranasal oxytocin has any effect on social skills, behaviors, or appetite in children with Prader-Willi syndrome.

Inclusion Criteria:

• Children with genetically confirmed PWS
• Ages at ≥ 5 years and ≤ 11 years (must start treatment prior to 11th birthday)
• Child must be in nutritional phase 2b or 3, as determined by the PI at each site.
• Must currently be on growth hormone treatment, and have been receiving growth hormone treatment for at least one year prior to screening date.
• Treatment cannot have been interrupted for more than 1 week within 3 months prior to screening date.
• Priority will be given to children currently enrolled in the RDCRN Natural History study

Exclusion Criteria:

• Inability to tolerate intranasal administration of medication
• Hepatic insufficiency (AST/ALT greater than 3 times the normal levels for age)
• Renal insufficiency (BUN/Creatinine greater than 3 times the normal levels for age)
• History of an abnormal ECG (as determined by a cardiologist). If there is any question about cardiac function, ECG reports will be reviewed with a cardiologist prior to enrollment in the study.
• Child not receiving growth hormone treatment
• Child with hypertension or hypotension for age and sex (blood pressure >97% for age and sex or blood pressure <3% for age and sex)
• Diabetes mellitus
• Pregnant or lactating.
• Schizophrenia or psychosis
• Taking any psychotropic medications