Oxytocin Trial in Prader-Willi Syndrome

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?

Study Overview

• Status: Completed
• Conditions: Prader Willi Syndrome
• Intervention / Treatment: Drug: Intranasal oxytocin; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92686
      • University of California, Irvine
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intranasal oxytocin; Intranasal oxytocin. 16 IU intranasal oxytocin x 5 days. One month interval between arms of treatment.	Drug: Intranasal oxytocin; This is a double-blind placebo controlled 2x2 study. Subjects will receive OT for 5 consecutive days during their 7 day stay. This will be followed by a wash out period of 4-6 weeks.; Other Names: Pitocin; Syntocinon
Placebo Comparator: Placebo; Placebo will be administered via nasal spray - 1 spray in each nostril x5 days.	Other: Placebo; This is a double-blind placebo controlled 2x2 study. Placebo will be given via intranasal spray, one spray in each nostril daily x 5 days. One month interval between arms of treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of intranasal oxytocin in children with Prader-Willi syndrome	Occurrence of adverse event, description and quantification of clinical and behavior severity, pre- and post- intranasal oxytocin and placebo administration.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of food intake in Prader-Willi syndrome	Quantitative evaluation of hyperphagia via the Hyperphagia Questionnaire obtained on days 1, 4 and 6 during the 7 day study protocol and conducted in the evening on these days. Score will range from 0 (no hyperphagia behaviors) to 96 (most severe hyperphagia behaviors). Additionally quantity of food consumed will be recorded on Days 1,4, and 6.	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of social effects of intranasal oxytocin in children with Prader-Willi syndrome	Evaluation of anxiety, food issues, irritability, social communication and behavioral issues will be measured on days 1, 4 and 6 using: Aberrant Behavior Checklist: Behavior rating scale used to measure behavior problems of children and adults with intellectual disabilities ages 6 - 54 years. Scores will range from 0 (no problem behaviors) to 174 (severe aberrant behaviors).; Social Responsiveness Scale:designed to measure the breadth of repetitive behaviors. Scores will range from 64 (no repetitive behaviors) to 260 (severe repetitive behaviors).; Repetitive Behavior Scales-Revised: Designed to measure the breadth of repetitive behaviors in autism spectrum disorder including: Ritualistic/Sameness Behavior; Stereotypic Behavior; Self-injurious Behavior; Compulsive Behavior; and Restricted Interests. Scores will range from 0 (no autistic behaviors) to 100 (severe autistic behaviors).	3 months
Effects of intranasal oxytocin on appetite-regulating hormones	Evaluation of plasma OT, ghrelin and other neuroendocrine hormones involved in appetite regulation (cortisol, orexin A, ghrelin, leptin, oxytocin, insulin).	3 months

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Jennifer L Miller, MD, University of Florida

Publications and helpful links

General Publications

• Tauber M, Mantoulan C, Copet P, Jauregui J, Demeer G, Diene G, Roge B, Laurier V, Ehlinger V, Arnaud C, Molinas C, Thuilleaux D. Oxytocin may be useful to increase trust in others and decrease disruptive behaviours in patients with Prader-Willi syndrome: a randomised placebo-controlled trial in 24 patients. Orphanet J Rare Dis. 2011 Jun 24;6:47. doi: 10.1186/1750-1172-6-47.

Helpful Links

• Oxytocin treatment in children with Prader-Willi syndrome: A double-blind, placebo-controlled, crossover study. Miller JL, Tamura R, Butler MG, Kimonis V, Sulsona C, Gold JA, Driscoll DJ. Am J Med Genet A. 2017 May;173(5):1243-1250.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: December 11, 2013
• First Submitted That Met QC Criteria: December 16, 2013
• First Posted (Estimate): December 17, 2013

Study Record Updates

• Last Update Posted (Actual): April 5, 2018
• Last Update Submitted That Met QC Criteria: April 4, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Oxytocin; Prader Willi syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Syndrome; Prader-Willi Syndrome; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: 5208-N