Tolerance of Intranasal Administration of OT in Prader-Willi Newborn Babies
Condition: Prader-Willi Syndrome
MeSH terms: Prader-Willi Syndrome
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Background: 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 insatiable hunger, 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. A deficit in the oxytocin (OT)-producing neurons of the
      paraventricular nucleus in the brain of these patients has been reported. In addition of its
      well-known anorexigenic effect, OT is involved in establishing and maintaining social codes.
      Indeed, we have recently shown in a double blind placebo study, that OT administration to
      adult patients with PWS significantly decreased depressive mood tendencies and tantrums while
      increasing trust in others with some data on a trend to decrease appetite with higher
      satiety. 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. These data, OT deficit in PWS, good tolerance of OT and its effect after intranasal
      administration in adult patients with PWS and the recent striking data obtained in the MAGEL2
      mouse model, prompted us to evaluate the tolerance of a single administration of intranasal
      OT in PWS newborns and its possible effect on suckling and food intake. Nowadays the
      diagnosis of PWS is done during the first months of life in our country. At this age,
      children still present with poor suckling suggesting that OT may be still efficient. Moreover
      in adult patients with PWS we have shown that OT improves some typical behavioral troubles.
      Therefore we first want to evaluate the tolerance of the intranasal administration of OT in 6
      infants with PWS genetically confirmed and its effect on suckling, milk intake and weight
      gain.
    

Detailed description: 
      We want to evaluate the tolerance of the intranasal administration of OT in 6 infants with
      PWS genetically confirmed and its effect on suckling, milk intake and weight gain. The three
      first patients will have single nasal administration of 2 IU of Oxytocin and, if no adverse
      event has been observed, the 3 following patients will have single nasal administration of 4
      IU of Oxytocin. We will monitor cardiac pulse, blood pressure, urine emission and measure
      biological safety parameters (glycemia, natremia and kaliemia). Video will be performed
      during 1 day before the drug administration and the 3 days after in order to qualify the
      suckling. Quantitative evaluation of the milk intake during each feeding and per day will be
      also evaluated. Biological parameters will be measured OT, ghrelin, others neuroendocrine
      hormones involved in appetite regulation (leptin, cortisol, insulin, GLP-1, PYY, pancreatic
      polypeptide, orexin A, aMSH) taking advantage of blood samples for safety biological
      measurements. These infants will stay 8 days (which is less than the mean duration of
      hospitalization of these infants) with data records by phone at 1 month and then have a final
      visit after 3 months.
    

Intervention name(s): Oxytocin
Intervention type(s): Drug
Intervention description(s): 2 ui intranasal administration for the 3 first patients, 4UI for the 3 following patients.
Intervention MeSH terms: Oxytocin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Prader-Willi, neonates, poor suckling