Oxytocin Intranasal Administrations in Children With Prader-Willi Syndrome Aged From 3 to 12 Years

Overview

Positive results in preclinical and clinical studies in adults and infants with Prader-Willi syndrome lead investigators to set up a new study in children with Prader-Willi syndrome. The objective of this study is to document effects of oxytocin intranasal administrations on behavioural troubles in children with Prader-Willi syndrome aged from 3 to 12 years.

Full Title of Study: “Effects of Intranasal Administrations of Oxytocin on Behavioural Troubles, Hyperphagia and Social Skills in Children With Prader-Willi Syndrome Aged From 3 to 12 Years.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: December 2019

Detailed Description

Two groups of patients will be constituted according to their age; "Group 1" children aged from 3 to 6 years (n = 20) and "Group 2" children aged from 7 to 12 years (n = 20). Within each group, subjects will be randomized to receive either oxytocin or placebo for 12 consecutive weeks. A second period of 12 consecutive oxytocin treatment weeks will then be performed for all patients, followed by a 4-week observation period to document effects after discontinuation of treatment.

Interventions

  • Drug: Oxytocin
    • The study drug is oxytocin in intra-nasal administration, Syntocinon®, reconditioned as a placebo-like spray. The dosage administered will be 8 International Unit, ie 1 spray (4 International Unit per spray) in each nostril per day for the first 12 weeks, in 3 and 6 years old patients. The dosage administered will be 16 International Unit or 2 sprays in each nostril per day for the first 12 weeks, in 3 to 6 years old patients.
  • Drug: Placebo
    • Placebo should be used as a spray, similar to that of the oxytocin. The dosage administered will be 1 spray in each nostril per day for the first 12 weeks in 3 to 6 years old patients. The dosage administered will be 2 sprays in each nostril per day for the first 12 weeks, in 7 to 12 years old patients.
  • Drug: Oxytocin
    • Each patient will receive oxytocin in open label (Syntocinon® not reconditioned) from week 13 to week 24 according to the same dosages.

Arms, Groups and Cohorts

  • Experimental: Oxytocin
    • Daily intranasal administrations of oxytocin for 12 weeks, followed by an open-label period of 12 weeks of oxytocin. Oxytocin dose will be 8 International Unit for patients aged from 3 to 6 years and 16 International Unit for patients aged from 7 to 12 years.
  • Placebo Comparator: Placebo
    • Daily intranasal administrations of placebo for 12 weeks, followed by an open-label period of 12 weeks of oxytocin. Oxytocin dose will be International Unit for patients aged from 3 to 6 years and 16 International Unit for patients aged from 7 to 12 years.

Clinical Trial Outcome Measures

Primary Measures

  • Evolution of behavioural troubles evaluated by the global score of Child Behavior Check List Questionnaire after 12 weeks of oxytocin/placebo treatment.
    • Time Frame: Week 12
    • It’s variation between inclusion and 12 weeks of total score total problems from the Child Behavior Check List Questionnaire.

Secondary Measures

  • Evaluation of hyperphagia after 12 weeks of oxytocin/placebo treatment.
    • Time Frame: Week 12
    • It is the variation of each of the three sub-scores obtained from the Dykens hyperphagia questionnaire between day 0 and week 12.
  • Evaluation of social skills after 12 weeks of oxytocin/placebo treatment.
    • Time Frame: Week 12
    • It is variation between day 0 and week 12 of the total score obtained from the social skills assessment questionnaire for children aged from 3 to 6 years and the Social Responsiveness Scale questionnaire for children aged from 7 to 12 years.
  • Evaluation of auto- and hetero-aggressive after 12 weeks of oxytocin/placebo treatment.
    • Time Frame: Week 12
    • It is variation between day 0 and week 12 of the total score obtained from the self-aggression assessment questionnaire.
  • Evaluation of psychopathology after 12 weeks of oxytocin/placebo treatment.
    • Time Frame: Week 12
    • It is the variation of the following sub-scores obtained from the Child Behaviour Check List questionnaire (only the following 3 subscales) between day 0 and week 12.
  • Evaluation of global clinical status after 12 weeks of oxytocin/placebo treatment.
    • Time Frame: Weeks 12
    • It is improvement of the patient’s overall clinical condition after 12 weeks of treatment with oxytocin/placebo. It’s assessed by the Clinical Global Impression Scale’s score. This scale of improvement of Clinical Global Impression is a 7-point ordinal qualitative scale of “very greatly improved” rated + 3 to “very strongly aggravated” rated -3. The result is expressed in total score which varies from -3 to +3.
  • Evaluation of acyl and desacyl ghrelin plasma levels after 12 weeks of oxytocin/placebo treatment.
    • Time Frame: Week 12
    • It is evolution of circulating levels of acylated and deacylated ghrelin will be the variations of these rates and the variation of the relationships between day 0 and week 12.
  • Evaluation of attentional abilities after 12 weeks of oxytocin/placebo treatment, for patients aged from 7 to 12 years at inclusion.
    • Time Frame: Week 12
    • It is evolution of attentional abilities is evaluated by a computerized test, the Attention Network Test.
  • Evaluation of metabolic brain resting state after 12 weeks of oxytocin/placebo treatment, for patients aged from 7 to 12 years at inclusion.
    • Time Frame: Week 12
    • It is evolution of metabolic brain resting state is evaluated by a magnetic resonance imaging to study the cerebral metabolism between day 0 and week 12.

Participating in This Clinical Trial

Inclusion Criteria

  • patient with a complete genetic diagnosis of Prader-Willi syndrome
  • patient treated by growth hormone for at least 1 year
  • patient naïve for oxytocin for at least 5 years

Exclusion Criteria

  • patient who do not accept intranasal administrations (major behavioural trouble)
  • patient with hepatic insufficiency : serum transaminases (SGOT, SGPT) higher than 3 times normal values for age
  • patient with renal insufficiency : serum creatinine higher than 3 times normal values for age
  • patient with an antecedent of abnormal electrocardiogram
  • patient with arterial hypertension or hypotension
  • patient with type 1 or 2 diabetes

Gender Eligibility: All

Minimum Age: 3 Years

Maximum Age: 12 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University Hospital, Toulouse
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Sophie ÇABAL-BERTHOUMIEU, Dr, Principal Investigator, Centre de référence du syndrome de Prader-Willi, Hôpital des Enfants
  • Overall Contact(s)
    • Sophie ÇABAL-BERTHOUMIEU, Dr, 5 34 55 74 32, cabal-berthoumieu.s@chu-toulouse.fr

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