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Evaluation of Tolerance, Suckling and Food Intake After Repeated Nasals Administrations of Oxytocin in PWS Infants (OTBB2)

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ClinicalTrials.gov Identifier: NCT02205034
Recruitment Status : Completed
First Posted : July 31, 2014
Last Update Posted : May 12, 2017
Sponsor:
Information provided by (Responsible Party):
University Hospital, Toulouse

Brief 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.

Condition or disease Intervention/treatment Phase
Prader Willi Syndrome Drug: oxytocin Phase 1 Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Tolerance, Suckling and Food Intake After Repeated Nasals Administrations of Oxytocin in PWS Infants
Study Start Date : May 2013
Actual Primary Completion Date : July 2014
Actual Study Completion Date : July 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Oxytocin

Arm Intervention/treatment
Active Comparator: first arm
4IU of oxytocin every other day
Drug: oxytocin
Intranasal administration
Other Name: Oxytocin (Syntocinon)

Active Comparator: second arm
4 IU of oxytocin daily
Drug: oxytocin
Intranasal administration
Other Name: Oxytocin (Syntocinon)

Active Comparator: third arm
4 IU of oxytocin twice daily
Drug: oxytocin
Intranasal administration
Other Name: Oxytocin (Syntocinon)




Primary Outcome Measures :
  1. Occurence of adverse event [ Time Frame: up to day 8 (Visit 8) ]
    Occurrence of adverse event, description and quantification of their severity, imputability to repeated intranasal administration of OT (4IU every other day, 4 IU daily, 4IU twice daily) during the 7 days following the first administration.


Secondary Outcome Measures :
  1. Efficacy, pathophysiological study [ Time Frame: Up to day 8 ]
    Preliminary study of efficacy on suckling and swallowing and quantity of milk intake/day infant-mother interactions before during and after feeding weight gain and growth Pathophysiological study of cerebral metabolism (fMRI bold) plasma levels of ghrelin and other peptides involved in feeding behaviour or energy metabolism


Other Outcome Measures:
  1. Pharmacokinetic study [ Time Frame: On day 2, 3, 4, 5, 6, 7, 8 ]
    Pharmacokinetic study : measurement of circulating oxytocin levels before administration and every 48hrs.



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Ages Eligible for Study:   1 Month to 5 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Infants with PWS genetically confirmed
  • Aged less than 5 months

Exclusion Criteria:

  • Infants presenting hepatic insufficiency
  • Infants presenting renal insufficiency
  • Infants with abnormal ECG

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02205034


Locations
France
Centre de réfrence Prader-Willi, Hospital of infants
Toulouse, France, 31059
Sponsors and Collaborators
University Hospital, Toulouse
Investigators
Principal Investigator: Maïthé TAUBER Endocrinologie pédiatrique, Hospital of Toulouse

Publications of Results:
Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT02205034     History of Changes
Other Study ID Numbers: 12 391 02
1239102 ( Other Grant/Funding Number: Toulouse University Hospital Funding )
First Posted: July 31, 2014    Key Record Dates
Last Update Posted: May 12, 2017
Last Verified: May 2017

Keywords provided by University Hospital, Toulouse:
Prader Willi

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