Early oxytocin treatment in infants with Prader-Willi syndrome is safe and is associated with better endocrine, metabolic and behavioral outcomes.

Gwenaelle Diene, Catherine Molinas, Jean-Pierre Salles, Marion Valette, Catherine Arnaud, Pierre Payoux, Maithé Tauber, Mélanie Glattard, Julie Cortadellas, Sandy Faye, Grégoire Benvegnu, Kader Boulanouar, Sophie Çabal

Journal: Orphanet journal of rare diseases 2025;20(1):96

PMID: 40025514

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Abstract

BACKGROUND

Oxytocin (OT) plays an important role in modulating behavior, social interactions and feeding. Prader-Willi syndrome (PWS), a rare genetic neurodevelopmental disorder, is a model of hypothalamic disorder including OT dysfunction. We previously showed that infants with PWS who had received an early short course (7 days) of intranasal OT treatment improved their oral and social skills. We aim to document the long-term tolerance and effects of early intranasal OT treatment on the disease trajectory.

METHODS

We performed a comparative clinical trial including the 17 children who had received OT as infants in our previous study and compared them to 17 PWS non-exposed children at 3-4 years old. Primary endpoint was the total communication score on the Vineland Adaptive Behavior Scales-2nd edition (VABS-II). Secondary endpoints were the other domains of VABS-II, behavior scored by the Child Behavior Checklist, feeding skills, endocrine and metabolic profiles, and brain connectivity on functional magnetic resonance imaging.

RESULTS

We documented the long-term safety of early OT treatment. The VABS-II communication score was not different between the two groups, defined as OT-exposed and non-exposed, whereas a trend toward a higher socialization score was found in the OT-exposed children (p = 0.06). Circulating IGF-1 and HDL cholesterol were significantly higher in the OT-exposed group (p < 0.05). OT-exposed children had normal acylated ghrelin levels, which were lower than those observed in non-exposed children (p = 0.06), and they displayed higher connectivity of the orbitofrontal cortex brain region.

CONCLUSION

Early OT treatment in infants with PWS is safe up to 3-4 years of age. OT-exposed children display better social, endocrine and metabolic outcomes. This study documents for the first time in human the biological window of opportunity of early OT treatment, which may change the trajectory of the PWS condition.

TRIAL REGISTRATION

Clinical trial NCT03081832 Retrospectively registered https://clinicaltrials.gov/search?cond=NCT03081832 .

Address: Centre de Référence Maladies Rares PRADORT (syndrome de PRADer-Willi et autres Obésités Rares avec Troubles du Comportement Alimentaire), Hôpital des Enfants, CHU Toulouse, Université Toulouse III Paul Sabatier, 330, Avenue de Grande Bretagne, TSA 70034, 31059, Toulouse Cedex 9, France.; CERPOP (Centre d'Epidémiologie et de Recherche en sante des POpulations), UMR 1295 Inserm, Université Toulouse III Paul Sabatier, Toulouse, France.; Centre de Référence Maladies Rares PRADORT (syndrome de PRADer-Willi et autres Obésités Rares avec Troubles du Comportement Alimentaire), Hôpital des Enfants, CHU Toulouse, Université Toulouse III Paul Sabatier, 330, Avenue de Grande Bretagne, TSA 70034, 31059, Toulouse Cedex 9, France.; Centre de Référence Maladies Rares PRADORT (syndrome de PRADer-Willi et autres Obésités Rares avec Troubles du Comportement Alimentaire), Hôpital des Enfants, CHU Toulouse, Université Toulouse III Paul Sabatier, 330, Avenue de Grande Bretagne, TSA 70034, 31059, Toulouse Cedex 9, France.; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity) Inserm UMR1291 - CNRS UMR5051, Université Toulouse III Paul Sabatier, Toulouse, France.; Centre de Référence Maladies Rares PRADORT (syndrome de PRADer-Willi et autres Obésités Rares avec Troubles du Comportement Alimentaire), Hôpital des Enfants, CHU Toulouse, Université Toulouse III Paul Sabatier, 330, Avenue de Grande Bretagne, TSA 70034, 31059, Toulouse Cedex 9, France.; Service Universitaire de Psychiatrie de l'Enfant et de l'Adolescent, CHU de Toulouse, Hôpital Purpan, Place du Dr Baylac, TSA 40031, 31059, Toulouse Cedex 9, France.; TOulouse NeuroImaging Center (TONIC), Université de Toulouse, Inserm UMR 1214, Université Toulouse III Paul Sabatier, Toulouse, France.; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity) Inserm UMR1291 - CNRS UMR5051, Université Toulouse III Paul Sabatier, Toulouse, France.; CERPOP (Centre d'Epidémiologie et de Recherche en sante des POpulations), UMR 1295 Inserm, Université Toulouse III Paul Sabatier, Toulouse, France.; Unité d'épidémiologie clinique, CHU Toulouse, Toulouse, France.; Centre de Référence Maladies Rares PRADORT (syndrome de PRADer-Willi et autres Obésités Rares avec Troubles du Comportement Alimentaire), Hôpital des Enfants, CHU Toulouse, Université Toulouse III Paul Sabatier, 330, Avenue de Grande Bretagne, TSA 70034, 31059, Toulouse Cedex 9, France. [email protected].; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity) Inserm UMR1291 - CNRS UMR5051, Université Toulouse III Paul Sabatier, Toulouse, France. [email protected].

DOI: 10.1186/s13023-025-03560-3

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https://assays.cancer.gov/non-CPTAC-2677

MeSH Terms: Child, Preschool, Female, Humans, Infant, Male, Oxytocin, Prader-Willi Syndrome