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| ID | Type | Description | Link |
|---|---|---|---|
| 1239102 | Other Grant/Funding Number | Toulouse University Hospital Funding |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| first arm | Active Comparator | 4IU of oxytocin every other day |
|
| second arm | Active Comparator | 4 IU of oxytocin daily |
|
| third arm | Active Comparator | 4 IU of oxytocin twice daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| oxytocin | Drug | Intranasal administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| Occurence of Adverse Event | 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. | up to day 8 (Visit 8) |
| Measure | Description | Time Frame |
|---|---|---|
| NOMAS Score | NOMAS score evaluate sucking/swallowing abilitites of infants during feeding; endpoint is the % of infants who reached a NOMAS score <= 10 (normal score) | Before and after 7 days of treatment |
| Videofluoroscopy of Swallowing Score |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Maïthé TAUBER | Endocrinologie pédiatrique, Hospital of Toulouse | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre de réfrence Prader-Willi, Hospital of infants | Toulouse | 31059 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28100688 | Result | 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. | |
| 28823614 |
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| ID | Title | Description |
|---|---|---|
| FG000 | First Arm | 4IU of oxytocin every other day oxytocin: Intranasal administration |
| FG001 | Second Arm | 4 IU of oxytocin daily oxytocin: Intranasal administration |
| FG002 | Third Arm | 4 IU of oxytocin twice daily oxytocin: Intranasal administration |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | First Arm | 4IU of oxytocin every other day oxytocin: Intranasal administration |
| BG001 | Second Arm | 4 IU of oxytocin daily oxytocin: Intranasal administration |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Occurence of Adverse Event | 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. | Posted | Number | number of adverse events | up to day 8 (Visit 8) |
|
everyday during the trial so during 7 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | First Arm | 4IU of oxytocin every other day oxytocin: Intranasal administration |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumopathy | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| constipation | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pr Maithe Tauber | CHU Toulouse | +33534558551 | tauber.mt@chu-toulouse.fr |
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| ID | Term |
|---|---|
| D011218 | Prader-Willi Syndrome |
| ID | Term |
|---|---|
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D010121 | Oxytocin |
| ID | Term |
|---|---|
| D010909 | Pituitary Hormones, Posterior |
| D010907 | Pituitary Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
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Videofluoroscopy of swallowing score (VFSS score)
| before and after 7 days of treatment |
| Result |
| 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. |
| 33232306 | Derived | 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. |
| BG002 | Third Arm | 4 IU of oxytocin twice daily oxytocin: Intranasal administration |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
4 IU of oxytocin twice daily oxytocin: Intranasal administration |
|
|
| Secondary | NOMAS Score | NOMAS score evaluate sucking/swallowing abilitites of infants during feeding; endpoint is the % of infants who reached a NOMAS score <= 10 (normal score) | Not Posted | Before and after 7 days of treatment | Participants |
| Secondary | Videofluoroscopy of Swallowing Score | Videofluoroscopy of swallowing score (VFSS score) | Not Posted | before and after 7 days of treatment | Participants |
| 0 |
| 6 |
| 1 |
| 6 |
| 4 |
| 6 |
| EG001 | Second Arm | 4 IU of oxytocin daily oxytocin: Intranasal administration | 0 | 6 | 0 | 6 | 5 | 6 |
| EG002 | Third Arm | 4 IU of oxytocin twice daily oxytocin: Intranasal administration | 0 | 6 | 0 | 6 | 4 | 6 |
| Gastro-oesophageal reflux disease | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Teething | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Hepatocellular injury | Hepatobiliary disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Rash maculopapular | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Conjunctivitis bacterial | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Culture urine positive | Investigations | MedDRA 10.0 | Non-systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Oral candidasis | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Infantile colic | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
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| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D025063 | Chromosome Disorders |
| D030342 | Genetic Diseases, Inborn |
| D000096803 | Imprinting Disorders |
| D009765 | Obesity |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |