Intranasal Oxytocin vs. Placebo for the Treatment of Hyperphagia in Prader-Willi Syndrome

Phase 2 Study: Intranasal Oxytocin vs. Placebo for the Treatment of Hyperphagia in Children and Adolescents With Prader-Willi Syndrome

This study is a phase 2 randomized double blind 8-week treatment trial of intranasal OXT vs. placebo in 50 subjects aged 5 to 17 years with PWS in order to assess IN-OXT's affect on measurements of (1) eating behaviors (2) repetitive behaviors (3) weight and body composition (4) quality of life (5) salivary OXT and hormone levels (including ghrelin, pancreatic polypeptide, peptide YY, GLP-1, insulin, glucagon, testosterone, and estrogen). If superior to placebo, this data will add to the current knowledge that OXT is an effective treatment for hyperphagia as well as other symptoms of PWS.

Funding Source- FDA OOPD

Study Overview

• Status: Recruiting
• Conditions: Hyperphagia; Prader-Willi Syndrome
• Intervention / Treatment: Drug: Intranasal Oxytocin (IN-OXT); Drug: Matched Placebo

Detailed Description

Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder caused by lack of expression of paternally derived imprinted material on chromosome 15q11-q13. PWS is characterized by mild to moderate intellectual disabilities, repetitive/compulsive behaviors and rigidity, social cognition deficits and severe hypotonia at birth, followed by the onset of hyperphagia later in life. Obesity is responsible for the majority of the morbidity and mortality associated with PWS, and compulsive eating behaviors are most responsible for diminishing the quality of life for caregivers and family members. Oxytocin has been implicated in the pathophysiology of PWS and there have been small studies of intranasal oxytocin (IN-OXT) in this population. To date, however, studies have not been adequately powered to detect significance in target symptoms of hyperphagia and associated symptoms of individuals with PWS. The primary goal of this study is to examine the safety and efficacy of IN-OXT on hyperphagia, as measured by the Hyperphagia Questionnaire-Clinical Trails, from baseline to week 8. Currently, there are no effective treatments available to manage hyperphagia in patients with PWS.

STUDY DESIGN: This is an 8-week double-blind, randomized study in 50 children with PWS aged 5-17. Participation involves 2 in-person visits to our program and 5 remote visits. Travel expenses will be reimbursed to participating families.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bonnie Taylor, PhD; Phone Number: 718-839-7530; Email: botaylor@montefiore.org

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10461
      • Recruiting
      • Montefiore Medical Center, Albert Einstein College of Medicine
      • Contact: Bonnie Taylor, PhD; Phone Number: 718-839-7530; Email: botaylor@montefiore.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female pediatric outpatients aged 5 to 17 years
2. Must be in PWS nutritional phase 2b or 3 as determined by PI
3. Must be on growth hormone treatment and have been receiving stable doses of growth hormone treatment for at least 3 months prior to screening date. Treatment cannot have been interrupted for more than one week within 3 months of screening.
4. Diagnosis of PWS confirmed by patient medical records.
5. A score of at least moderate severity on the Hyperphagia Questionnaire for Clinical Trials at both screening and baseline visits.
6. Stable dosages of hormone treatments (including testosterone and estrogen supplements) for 4 weeks prior to randomization and for the duration of the study.
7. Stable dosages of metabolic treatments that could affect appetite (including metformin) for 4 weeks prior to randomization and for the duration of the study.
8. Physical exam and laboratory results that are within the normal range for individuals with PWS.
9. Presence of a parent/caregiver/guardian that is able to consent for their participation and complete assessments regarding the child's development and behavior change throughout the study.

Exclusion Criteria:

1. Exposure to any investigational agent in the 30 days prior to randomization.
2. Child not receiving growth hormone treatment
3. Children weighing less than 40 lbs
4. Children with unstable Type 2 Diabetes confirmed by Hemoglobin A1C levels at screening
5. Children with unstable medical co-morbidities at baseline.
6. Children with active upper respiratory infections at screening.
7. A primary psychiatric diagnosis other than ASD, including bipolar disorder, psychosis, schizophrenia, PTSD or MDD. These patients will be excluded due to potential confounding results.
8. Pregnant or lactating patients or patients who will not agree to use a double barrier method of contraception. IN-OXT has not been studied in pregnant or lactating women.
9. Females using an estrogen-based contraceptive. As an alternative to an estrogen based contraceptive, subjects will be counseled to use progesterone-based contraceptives; cervical cap; cervical sponges; or spermicidal foam in combination with a condom. Subjects will need to use a double barrier method to be in the study.
10. A medical condition that might interfere with the conduct of the study, confound interpretation of study results or endanger the subject's well-being.
11. A known diagnosis of Rett's Syndrome of Childhood Disintegrative Disorder or marked sensory impairment such as deafness or blindness.
12. Subjects who have changes in allied health therapies, behavioral or educational interventions within four weeks prior to randomization other than those associated with school holidays.
13. Subjects who have had changes in medications or medication doses of risperidone, aripiprazole, other antipsychotic medications, clonidine, guanfacine, stimulants or anti-convulsants within four weeks of randomization.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Intranasal Oxytocin (IN-OXT); Syntocinon (synthetic oxytocin) will be used in this protocol. Each subject will receive a dose of 16 IU QD and will be instructed to inhale 2 puffs per nostril (4 IU each).	Drug: Intranasal Oxytocin (IN-OXT); Each subject will receive a dose of 16 IU QD, and will be instructed to inhale 2 puffs per nostril every day (4 IU each). If needed, treatment will be titrated due to side effects or non-response.; Other Names: Syntocinon
Placebo Comparator: Placebo Comparator: Matched Placebo; Each subject will receive a dose of 16 IU QD, and will be instructed to inhale 2 puffs per nostril (4 IU each).	Drug: Matched Placebo; Each subject will receive a dose of 16 IU QD, and will be instructed to inhale 2 puffs per nostril every day (4 IU each). If needed, treatment will be titrated due to side effects or non-response.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hyperphagia Questionnaire for Clinical Trials	Assesses Eating Behaviors and Hyperphagia in PWS. Repeated Measures Analysis.	From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Repetitive Behavior Scale Revised (RBS-R)	Change in Repetitive Behavior Scale (RBS-R) from baseline to endpoint	From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks)
BMI	Change in BMI from baseline to endpoint	From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks)
Body Composition	Change in Body Composition (measured via bioelectrical impedance analysis) from baseline to endpoint	From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks)
World Health Organization Quality of Life Questionnaire (WHOQOL)	Change in World Health Organization Quality of Life Questionnaire from baseline to endpoint	From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks)
Aberrant Behavior Checklist	Change in Aberrant Behavior Checklist (ABC) from baseline to Endpoint.	From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks)
Salivary Oxytocin Concentration	Change in Salivary Oxytocin Concentration from baseline to endpoint	From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks)
Caregiver Strain Questionnaire	Change in Caregiver Strain Questionnaire from baseline to endpoint	From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks)
Montefiore-Einstein Rigidity Scale-Revised PWS (MERS-PWS):	Change in three domains of rigid behavior from baseline to endpoint	From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Automated, Self-Administered, 24 Hour Recall Diary System	Change in ASA 24: Automated, Self-Administered, 24 Hour Recall Diary System from baseline to endpoint	From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks)
Relationship between weight-based dosing and hyperphagia treatment response		From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks)
Hormone levels (Ghrelin, pancreatic polypeptide, peptide YY, GLP-1, insulin, glucagon, testosterone, and estrogen)	Change in hormone levels (ghrelin, pancreatic polypeptide, peptide YY, GLP-1, insulin, glucagon, testosterone, and estrogen) from baseline to endpoint.	From Randomization at Baseline until Endpoint at Week 8 (Change over 8 weeks)

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Investigators: Principal Investigator: Eric Hollander, MD, Albert Einstein College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2018
• Primary Completion (Anticipated): August 31, 2023
• Study Completion (Anticipated): August 31, 2023

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: June 21, 2017
• First Posted (Actual): June 23, 2017

Study Record Updates

• Last Update Posted (Actual): August 22, 2022
• Last Update Submitted That Met QC Criteria: August 19, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Prader-Willi Syndrome; Hyperphagia
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Signs and Symptoms, Digestive; Overnutrition; Nutrition Disorders; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Syndrome; Prader-Willi Syndrome; Hyperphagia; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: 2017-8076; FD-R-05106-01 (Other Grant/Funding Number: FDA-OOPD)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No