Tolerance of Intranasal Administration of OT in Prader-Willi Newborn Babies

NCT01548521 | Completed Phase 1

• 1 other identifier: 10 152 02
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Prader-Willi Syndrome

Keywords

Prader-Willi, neonates, poor suckling

Outcome Measures

Primary Outcomes (1)

• Occurrence of adverse event, description and quantification of their severity, imputability to oxytocin administration.

  up to day 8

Secondary Outcomes (2)

• Quantitative evaluation of food intake

  from day 1 to month 3

• Evaluation of plasmatic OT, ghrelin and others neuroendocrine hormones involved in appetite regulation (leptin, cortisol, insulin, GLP-1, PYY, pancratic polypeptide, orexin A, aMSH)

  from day 1 to month 3

Study Arms (1)

Oxytocin

EXPERIMENTAL

Drug: Oxytocin

Interventions

Oxytocin DRUG

2 ui intranasal administration for the 3 first patients, 4UI for the 3 following patients.

Oxytocin

Eligibility Criteria

• Age: 15 Days - 5 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• neonates with genetic diagnosis of Prader-Willi syndrome
• aged from 15 days to 5 months

You may not qualify if:

• exclusive tube feeding
• arrhythmia

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (1)

Children Hospital of Toulouse Purpan

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Prader-Willi Syndrome

Interventions

Oxytocin

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Maithe TAUBER, MD

  Hospital of Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2011
• First Posted: March 8, 2012
• Study Start: July 1, 2011
• Primary Completion: February 1, 2012
• Study Completion: April 1, 2012
• Last Updated: February 23, 2017

Record last verified: 2017-02

Locations

FR (1)