Evaluation of Tolerance, Suckling and Food Intake After Repeated Nasals Administrations of Oxytocin in PWS Infants

Study Overview
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Brief Summary
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The Prader-Willi syndrome (PWS) includes severe neonatal hypotonia with impaired suckling leading to failure to thrive in the most severe cases, subsequently followed by an early onset of morbid obesity with hyperphagia and deficit of satiety, combined with other endocrine dysfunction probably due to hypothalamic dysfunction. The pathophysiological mechanism of the occurrence of the 2 main nutritional phases of PWS is unknown. Swaab reported a deficit in the oxytocin (OT)-producing neurons of the paraventricular nucleus in the brain of these patients. In addition of its well-known anorexigenic effect, OT is involved in establishing and maintaining social codes. Moreover in a PWS mouse model generated from a MAGEL2 KO gene a single OT injection at 5 hr of life prevent the early death observed in 50 % of the new born mice by recovering normal suckling. Interestingly this effect is no longer observed if OT injection takes place later. Our hypothesis is that early administration of OT in babies with PWS may improve suckling and possibly infant-mother interactions. In our recent study (manuscript in preparation), we have shown that a single intranasal administration of OT is well tolerated. This escalating dose study is designed to evaluate the tolerance of repeated intranasal administration of OT in 3 steps (4IU every other day, 4 IU daily, 4IU twice daily) in babies younger than 5 months with PWS.

Detailed Description
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Prader-Willi syndrome (PWS) is a rare, complex multisystem genetic disorder arising from the lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13. The syndrome includes severe neonatal hypotonia with impaired suckling leading to failure to thrive in the most severe cases, subsequently followed by an early onset of morbid obesity with hyperphagia and deficit of satiety, combined with other endocrine dysfunction probably due to hypothalamic dysfunction. The pathophysiological mechanism of the occurrence of the 2 main nutritional phases of PWS is unknown. Swaab reported a deficit in the oxytocin (OT)-producing neurons of the paraventricular nucleus in the brain of these patients. In addition of its well-known anorexigenic effect, OT is involved in establishing and maintaining social codes. Moreover in a PWS mouse model generated from a MAGEL2 KO gene a single OT injection at 5 hr of life prevent the early death observed in 50 % of the new born mice by recovering normal suckling. Interestingly this effect is no longer observed if OT injection takes place later. Our hypothesis is that early administration of OT in babies with PWS may improve suckling and possibly infant-mother interactions. In our recent study (manuscript in preparation), we have shown that a single intranasal administration of OT is well tolerated. This escalating dose study is designed to evaluate the tolerance of repeated intranasal administration of OT in 3 steps (4IU every other day, 4 IU daily, 4IU twice daily) in babies younger than 5 months with PWS.

Official Title
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Evaluation of Tolerance, Suckling and Food Intake After Repeated Nasals Administrations of Oxytocin in PWS Infants

Conditions
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Prader Willi Syndrome

Intervention / Treatment
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* Drug: oxytocin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants with PWS genetically confirmed Aged less than 5 months Exclusion Criteria: Infants presenting hepatic insufficiency Infants presenting renal insufficiency Infants with abnormal ECG

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 5 Months

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: first arm<br>4IU of oxytocin every other day | Drug: oxytocin<br>* Intranasal administration<br>* Other names: Oxytocin (Syntocinon);|
| Active Comparator: second arm<br>4 IU of oxytocin daily | Drug: oxytocin<br>* Intranasal administration<br>* Other names: Oxytocin (Syntocinon);|
| Active Comparator: third arm<br>4 IU of oxytocin twice daily | Drug: oxytocin<br>* Intranasal administration<br>* Other names: Oxytocin (Syntocinon);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurence of Adverse Event | Occurrence of adverse event, description and quantification of their severity, imputability to repeated intranasal administration of OT (4IU every other day, 4 IU daily, 4IU twice daily) during the 7 days following the first administration. | up to day 8 (Visit 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NOMAS Score | NOMAS score evaluate sucking/swallowing abilitites of infants during feeding; endpoint is the % of infants who reached a NOMAS score <= 10 (normal score) | Before and after 7 days of treatment | 
| Videofluoroscopy of Swallowing Score | Videofluoroscopy of swallowing score (VFSS score) | before and after 7 days of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prader Willi