Oxytocin Intranasal Administrations in Children With Prader-Willi Syndrome Aged From 3 to 12 Years

NCT03114371 | Completed

• 2 other identifiers: 15 7837 032016-003273-18
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Positive results in preclinical and clinical studies in adults and infants with Prader-Willi syndrome lead investigators to set up a new study in children with Prader-Willi syndrome. The objective of this study is to document effects of oxytocin intranasal administrations on behavioural troubles in children with Prader-Willi syndrome aged from 3 to 12 years.

Conditions

Prader-Willi Syndrome

Keywords

Prader-Willi syndrome; Oxytocin; Behavioural troubles

Outcome Measures

Primary Outcomes (1)

• Evolution of behavioural troubles evaluated by the global score of Child Behavior Check List Questionnaire after 12 weeks of oxytocin/placebo treatment.

  It's variation between inclusion and 12 weeks of total score total problems from the Child Behavior Check List Questionnaire.

  Week 12

Secondary Outcomes (8)

• Evaluation of hyperphagia after 12 weeks of oxytocin/placebo treatment.

  Week 12

• Evaluation of social skills after 12 weeks of oxytocin/placebo treatment.

  Week 12

• Evaluation of auto- and hetero-aggressive after 12 weeks of oxytocin/placebo treatment.

  Week 12

• Evaluation of psychopathology after 12 weeks of oxytocin/placebo treatment.

  Week 12

• Evaluation of global clinical status after 12 weeks of oxytocin/placebo treatment.

  Weeks 12

Study Arms (2)

Oxytocin

EXPERIMENTAL

Daily intranasal administrations of oxytocin for 12 weeks, followed by an open-label period of 12 weeks of oxytocin. Oxytocin dose will be 8 International Unit for patients aged from 3 to 6 years and 16 International Unit for patients aged from 7 to 12 years.

Drug: Oxytocin

Placebo

PLACEBO COMPARATOR

Daily intranasal administrations of placebo for 12 weeks, followed by an open-label period of 12 weeks of oxytocin. Oxytocin dose will be International Unit for patients aged from 3 to 6 years and 16 International Unit for patients aged from 7 to 12 years.

Drug: Placebo; Drug: Oxytocin

Interventions

Oxytocin DRUG

The study drug is oxytocin in intra-nasal administration, Syntocinon®, reconditioned as a placebo-like spray. The dosage administered will be 8 International Unit, ie 1 spray (4 International Unit per spray) in each nostril per day for the first 12 weeks, in 3 and 6 years old patients. The dosage administered will be 16 International Unit or 2 sprays in each nostril per day for the first 12 weeks, in 3 to 6 years old patients.

Also known as: Intranasal administration of oxytocin (Week 1 to 12)

Oxytocin

Placebo DRUG

Placebo should be used as a spray, similar to that of the oxytocin. The dosage administered will be 1 spray in each nostril per day for the first 12 weeks in 3 to 6 years old patients. The dosage administered will be 2 sprays in each nostril per day for the first 12 weeks, in 7 to 12 years old patients.

Also known as: Intranasal administration of placebo (Week 1 to 12)

Placebo

Eligibility Criteria

• Age: 3 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• patient with a complete genetic diagnosis of Prader-Willi syndrome
• patient treated by growth hormone for at least 1 year
• patient naïve for oxytocin for at least 5 years

You may not qualify if:

• patient who do not accept intranasal administrations (major behavioural trouble)
• patient with hepatic insufficiency : serum transaminases (SGOT, SGPT) higher than 3 times normal values for age
• patient with renal insufficiency : serum creatinine higher than 3 times normal values for age
• patient with an antecedent of abnormal electrocardiogram
• patient with arterial hypertension or hypotension
• patient with type 1 or 2 diabetes

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (1)

Centre de référence du syndrome de Prader-Willi Hôpital des Enfants

Toulouse, 31059, France

Location

Related Publications (21)

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• Dykens EM, Maxwell MA, Pantino E, Kossler R, Roof E. Assessment of hyperphagia in Prader-Willi syndrome. Obesity (Silver Spring). 2007 Jul;15(7):1816-26. doi: 10.1038/oby.2007.216.

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  PMID: 17598872 BACKGROUND

• Einfeld SL, Smith E, McGregor IS, Steinbeck K, Taffe J, Rice LJ, Horstead SK, Rogers N, Hodge MA, Guastella AJ. A double-blind randomized controlled trial of oxytocin nasal spray in Prader Willi syndrome. Am J Med Genet A. 2014 Sep;164A(9):2232-9. doi: 10.1002/ajmg.a.36653. Epub 2014 Jun 30.

  PMID: 24980612 BACKGROUND

• Fan J, McCandliss BD, Sommer T, Raz A, Posner MI. Testing the efficiency and independence of attentional networks. J Cogn Neurosci. 2002 Apr 1;14(3):340-7. doi: 10.1162/089892902317361886.

  PMID: 11970796 BACKGROUND

• Goldstone AP, Holland AJ, Butler JV, Whittington JE. Appetite hormones and the transition to hyperphagia in children with Prader-Willi syndrome. Int J Obes (Lond). 2012 Dec;36(12):1564-70. doi: 10.1038/ijo.2011.274. Epub 2012 Jan 24.

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• Guastella AJ, Einfeld SL, Gray KM, Rinehart NJ, Tonge BJ, Lambert TJ, Hickie IB. Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry. 2010 Apr 1;67(7):692-4. doi: 10.1016/j.biopsych.2009.09.020. Epub 2009 Nov 7.

  PMID: 19897177 BACKGROUND

• Guastella AJ, Gray KM, Rinehart NJ, Alvares GA, Tonge BJ, Hickie IB, Keating CM, Cacciotti-Saija C, Einfeld SL. The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: a randomized controlled trial. J Child Psychol Psychiatry. 2015 Apr;56(4):444-52. doi: 10.1111/jcpp.12305. Epub 2014 Aug 2.

  PMID: 25087908 BACKGROUND

• Hall SS, Lightbody AA, McCarthy BE, Parker KJ, Reiss AL. Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome. Psychoneuroendocrinology. 2012 Apr;37(4):509-18. doi: 10.1016/j.psyneuen.2011.07.020. Epub 2011 Aug 20.

  PMID: 21862226 BACKGROUND

• Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E. Oxytocin increases trust in humans. Nature. 2005 Jun 2;435(7042):673-6. doi: 10.1038/nature03701.

  PMID: 15931222 BACKGROUND

• Lischke A, Gamer M, Berger C, Grossmann A, Hauenstein K, Heinrichs M, Herpertz SC, Domes G. Oxytocin increases amygdala reactivity to threatening scenes in females. Psychoneuroendocrinology. 2012 Sep;37(9):1431-8. doi: 10.1016/j.psyneuen.2012.01.011. Epub 2012 Feb 23.

  PMID: 22365820 BACKGROUND

• MacDonald E, Dadds MR, Brennan JL, Williams K, Levy F, Cauchi AJ. A review of safety, side-effects and subjective reactions to intranasal oxytocin in human research. Psychoneuroendocrinology. 2011 Sep;36(8):1114-26. doi: 10.1016/j.psyneuen.2011.02.015. Epub 2011 Mar 23.

  PMID: 21429671 BACKGROUND

• Miller JL, Lynn CH, Driscoll DC, Goldstone AP, Gold JA, Kimonis V, Dykens E, Butler MG, Shuster JJ, Driscoll DJ. Nutritional phases in Prader-Willi syndrome. Am J Med Genet A. 2011 May;155A(5):1040-9. doi: 10.1002/ajmg.a.33951. Epub 2011 Apr 4.

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• Schaller F, Watrin F, Sturny R, Massacrier A, Szepetowski P, Muscatelli F. A single postnatal injection of oxytocin rescues the lethal feeding behaviour in mouse newborns deficient for the imprinted Magel2 gene. Hum Mol Genet. 2010 Dec 15;19(24):4895-905. doi: 10.1093/hmg/ddq424. Epub 2010 Sep 28.

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• Skokauskas N, Sweeny E, Meehan J, Gallagher L. Mental health problems in children with prader-willi syndrome. J Can Acad Child Adolesc Psychiatry. 2012 Aug;21(3):194-203.

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• Swaab DF, Purba JS, Hofman MA. Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader-Willi syndrome: a study of five cases. J Clin Endocrinol Metab. 1995 Feb;80(2):573-9. doi: 10.1210/jcem.80.2.7852523.

  PMID: 7852523 BACKGROUND

• Tauber M, Mantoulan C, Copet P, Jauregui J, Demeer G, Diene G, Roge B, Laurier V, Ehlinger V, Arnaud C, Molinas C, Thuilleaux D. Oxytocin may be useful to increase trust in others and decrease disruptive behaviours in patients with Prader-Willi syndrome: a randomised placebo-controlled trial in 24 patients. Orphanet J Rare Dis. 2011 Jun 24;6:47. doi: 10.1186/1750-1172-6-47.

  PMID: 21702900 BACKGROUND

• van Lieshout CF, de Meyer RE, Curfs LM, Koot HM, Fryns JP. Problem behaviors and personality of children and adolescents with Prader-Willi syndrome. J Pediatr Psychol. 1998 Apr;23(2):111-20. doi: 10.1093/jpepsy/23.2.111.

  PMID: 9585637 BACKGROUND

• Yatawara CJ, Einfeld SL, Hickie IB, Davenport TA, Guastella AJ. The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial. Mol Psychiatry. 2016 Sep;21(9):1225-31. doi: 10.1038/mp.2015.162. Epub 2015 Oct 27.

  PMID: 26503762 BACKGROUND

MeSH Terms

Conditions

Prader-Willi Syndrome

Interventions

Oxytocin

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Sophie ÇABAL-BERTHOUMIEU, Dr

  Centre de référence du syndrome de Prader-Willi, Hôpital des Enfants

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The packaging, presentation and labelling of the bottles used during the blind phase will guarantee the blindness to the healthcare team and the patient. The allocation of the treatment arms to each treatment number will be carried out according to the randomization table established beforehand. Until the end of the study, neither the investigating physician nor the patient will know the group to which the patient has been randomly assigned.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Children will receive after randomization either placebo or oxytocin administration (daily intranasal) for a total duration of 12 consecutive weeks.

Study Record Dates

• First Submitted: March 10, 2017
• First Posted: April 14, 2017
• Study Start: November 28, 2016
• Primary Completion: January 1, 2019
• Study Completion: January 11, 2019
• Last Updated: November 12, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)