Tolerance of Intranasal Administration of OT in Prader-Willi Newborn Babies
Status:
Completed
Trial end date:
2012-04-01
Target enrollment:
Participant gender:
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.