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

NCT ID: NCT02205034

Last Updated: 2024-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2014-07-31

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.

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.

Conditions

Prader Willi Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

first arm

4IU of oxytocin every other day

Group Type: ACTIVE_COMPARATOR

oxytocin

Intervention Type: DRUG

Intranasal administration

second arm

4 IU of oxytocin daily

Group Type: ACTIVE_COMPARATOR

oxytocin

Intervention Type: DRUG

Intranasal administration

third arm

4 IU of oxytocin twice daily

Group Type: ACTIVE_COMPARATOR

oxytocin

Intervention Type: DRUG

Intranasal administration

Interventions

oxytocin

Intranasal administration

Intervention Type: DRUG

Other Intervention Names

Oxytocin (Syntocinon)

Eligibility 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

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 5 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maïthé TAUBER

Role: PRINCIPAL_INVESTIGATOR

Endocrinologie pédiatrique, Hospital of Toulouse

Locations

Centre de réfrence Prader-Willi, Hospital of infants

Toulouse, , France

Countries

France

References

Tauber M, Boulanouar K, Diene G, Cabal-Berthoumieu S, Ehlinger V, Fichaux-Bourin P, Molinas C, Faye S, Valette M, Pourrinet J, Cessans C, Viaux-Sauvelon S, Bascoul C, Guedeney A, Delhanty P, Geenen V, Martens H, Muscatelli F, Cohen D, Consoli A, Payoux P, Arnaud C, Salles JP. The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader-Willi Syndrome. Pediatrics. 2017 Feb;139(2):e20162976. doi: 10.1542/peds.2016-2976.

Reference Type: RESULT

PMID: 28100688 (View on PubMed)

Viaux-Savelon S, Rosenblum O, Guedeney A, Diene G, Cabal-Berthoumieu S, Fichaux-Bourin P, Molinas C, Faye S, Valette M, Bascoul C, Cohen D, Tauber M. Dyssynchrony and perinatal psychopathology impact of child disease on parents-child interactions, the paradigm of Prader Willi syndrom. J Physiol Paris. 2016 Nov;110(4 Pt B):427-433. doi: 10.1016/j.jphysparis.2017.08.001. Epub 2017 Sep 1.

Reference Type: RESULT

PMID: 28823614 (View on PubMed)

Borie AM, Dromard Y, Guillon G, Olma A, Manning M, Muscatelli F, Desarmenien MG, Jeanneteau F. Correction of vasopressin deficit in the lateral septum ameliorates social deficits of mouse autism model. J Clin Invest. 2021 Jan 19;131(2):e144450. doi: 10.1172/JCI144450.

Reference Type: DERIVED

PMID: 33232306 (View on PubMed)

Other Identifiers

1239102

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

12 391 02

Identifier Type: -

Identifier Source: org_study_id