Evaluation of Tolerance, Suckling and Food Intake After Repeated Nasals Administrations of Oxytocin in PWS Infants
Condition: Prader Willi Syndrome
MeSH terms: Prader-Willi Syndrome
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): oxytocin
Intervention type(s): Drug
Intervention description(s): Intranasal administration
Other intervention name(s): Oxytocin (Syntocinon)
Intervention MeSH terms: Oxytocin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Prader Willi