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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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.

Conditions
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Prader-Willi Syndrome

Intervention / Treatment
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* Drug: Oxytocin
* Drug: Placebo
* Drug: Oxytocin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Children will receive after randomization either placebo or oxytocin administration (daily intranasal) for a total duration of 12 consecutive weeks.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxytocin<br>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. | Drug: Oxytocin<br>* 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.<br>* Other names: Intranasal administration of oxytocin (Week 1 to 12);Drug: Oxytocin<br>* Each patient will receive oxytocin in open label (Syntocinon® not reconditioned) from week 13 to week 24 according to the same dosages.<br>* Other names: Intranasal administration of oxytocin (Week 13 to 24);|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* 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.<br>* Other names: Intranasal administration of placebo (Week 1 to 12);Drug: Oxytocin<br>* Each patient will receive oxytocin in open label (Syntocinon® not reconditioned) from week 13 to week 24 according to the same dosages.<br>* Other names: Intranasal administration of oxytocin (Week 13 to 24);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of behavioural troubles evaluated by the global score of Child Behavior Check List Questionnaire after 12 weeks of oxytocin/placebo treatment. | It's variation between inclusion and 12 weeks of total score total problems from the Child Behavior Check List Questionnaire. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of hyperphagia after 12 weeks of oxytocin/placebo treatment. | It is the variation of each of the three sub-scores obtained from the Dykens hyperphagia questionnaire between day 0 and week 12. | Week 12 | 
| Evaluation of social skills after 12 weeks of oxytocin/placebo treatment. | 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. | Week 12 | 
| Evaluation of auto- and hetero-aggressive after 12 weeks of oxytocin/placebo treatment. | It is variation between day 0 and week 12 of the total score obtained from the self-aggression assessment questionnaire. | Week 12 | 
| Evaluation of psychopathology after 12 weeks of oxytocin/placebo treatment. | 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. | Week 12 | 
| Evaluation of global clinical status after 12 weeks of oxytocin/placebo treatment. | 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. | Weeks 12 | 
| Evaluation of acyl and desacyl ghrelin plasma levels after 12 weeks of oxytocin/placebo treatment. | 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. | Week 12 | 
| Evaluation of attentional abilities after 12 weeks of oxytocin/placebo treatment, for patients aged from 7 to 12 years at inclusion. | It is evolution of attentional abilities is evaluated by a computerized test, the Attention Network Test. | Week 12 | 
| Evaluation of metabolic brain resting state after 12 weeks of oxytocin/placebo treatment, for patients aged from 7 to 12 years at inclusion. | 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. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Behavioural troubles, Prader-Willi syndrome, Oxytocin