Tolerance of Intranasal Administration of OT in Prader-Willi Newborn Babies (OTBB)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Toulouse
ClinicalTrials.gov Identifier:
NCT01548521
First received: December 30, 2011
Last updated: June 20, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Prader-Willi Syndrome.
Drug: Oxytocin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Tolerance of Intranasal Administration of OT in Prader-Willi Newborn Babies and Effect on Suck and Food Intake.

Resource links provided by NLM:


Further study details as provided by University Hospital, Toulouse:

Primary Outcome Measures:
  • Occurrence of adverse event, description and quantification of their severity, imputability to oxytocin administration. [ Time Frame: up to day 8 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Quantitative evaluation of food intake [ Time Frame: from day 1 to month 3 ] [ Designated as safety issue: No ]
    food intake is measured in ml

  • Evaluation of plasmatic OT, ghrelin and others neuroendocrine hormones involved in appetite regulation (leptin, cortisol, insulin, GLP-1, PYY, pancratic polypeptide, orexin A, aMSH) [ Time Frame: from day 1 to month 3 ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: July 2011
Study Completion Date: April 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: one arm : oxytocin Drug: Oxytocin
2 ui intranasal administration for the 3 first patients, 4UI for the 3 following patients.

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.

  Eligibility

Ages Eligible for Study:   up to 5 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • exclusive tube feeding
  • arrhythmia
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01548521

Locations
France
Children Hospital of Toulouse Purpan
Toulouse, France, 31059
Sponsors and Collaborators
University Hospital, Toulouse
Investigators
Principal Investigator: Maithe TAUBER, MD Hospital of Toulouse
  More Information

No publications provided

Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT01548521     History of Changes
Other Study ID Numbers: 10 152 02
Study First Received: December 30, 2011
Last Updated: June 20, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Toulouse:
Prader-Willi, neonates, poor suckling

Additional relevant MeSH terms:
Prader-Willi Syndrome
Abnormalities, Multiple
Chromosome Disorders
Congenital Abnormalities
Genetic Diseases, Inborn
Intellectual Disability
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Nutrition Disorders
Obesity
Overnutrition
Oxytocin
Oxytocics
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014