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

Phase 1

Completed

Conditions: Prader Willi Syndrome

Interventions: Drug: oxytocin

Registration Number: NCT02205034

Lead Sponsor: University Hospital, Toulouse

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 18

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
first arm	oxytocin	4IU of oxytocin every other day
third arm	oxytocin	4 IU of oxytocin twice daily
second arm	oxytocin	4 IU of oxytocin daily

Primary Outcome Measures

Name	Time	Method
Occurence of Adverse Event	up to day 8 (Visit 8)	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.

Secondary Outcome Measures

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