Intranasal administration of oxytocin in children with Prader-Willi Syndrome. A randomized, open-label, cross-over trial of different treatment regimens of oxytocin administration. Effects on eating behaviour and social behaviour.

INTERVENTION: Trade Name: Syntocinon nasal spray Product Name: oxytocin Product Code: oxytocin Pharmaceutical Form: Nasal spray CONDITION: Prader‐Willi syndrome ; MedDRA version: 19.0 Level: PT Classification code 10036476 Term: Prader‐Willi syndrome System Organ Class: 10010331 ‐ Congenital, familial and genetic disorders Therapeutic area: Diseases [C] ‐ Hormonal diseases [C19] PRIMARY OUTCOME: Main Objective: ‐ To evaluate the effects of long‐term intranasal oxytocin on social behaviour in children with PWS; ‐ To evaluate the effects of long‐term intranasal oxytocin administration on appetite, satiety, food intake and food seeking behaviour in children with PWS; ‐ To investigate if there is a difference in the efficacy of oxytocin if adminstered in different doses and frequencies Primary end point(s): Changes in social and food related behaviour assessed by:; ‐ Oxytocin Study Questionnaire; ‐ VISK Secondary Objective: To evaluate oxytocin levels in blood and saliva samples before, during and after intranasal oxytocin treatment in different doses and frequencies in children with PWS; ‐ To evaluate the effects of long‐term intranasal oxytocin administration in different doses and frequencies in relation to: BMI, IGF‐1 and IGF‐BP3 levels, fMRI (BOLD response); Timepoint(s) of evaluation of this end point: Studygroup 1: ; Day 1: baseline assessments in the hospital, first administration of oxytocin followed by observation period and instruction of administration; Day 2‐month 6: administration of oxytocin one/twice a day every day at home; ‐ 6 months: hospital visit and assessments as mentioned on day 1; ‐ Mont 6‐month 7: wash‐out period; ‐ 7 months: parents fill out a questionnaire at home. Start other dosing regimen. ; Month 7‐month 13: administration of oxytocin once/twice daily every day at home; 13 months: hospital visit and assessment as mentioned on day 1; ; For studygroup 2 assessments will be done on day 1 (hospital), at 3 months (hospital), at 4 months (questionnaire at home), 7 months (hospital); INCLUSION CRITERIA: In order to be eligible to participate in this study, a subject must meet all of the following criteria: ‐ Genetically confirmed diagnosis of Prader‐Willi syndrome ‐ Age between 3 and 16 years ‐ Currently on growth hormone treatment for at least 1 year ‐ Behavioural problems (for example temper tantrums and autistic behaviour) and/or be in nutritional phase 2b or 3 according to Miller. For fMRI: age > 6 years Are the trial subjects under 18? yes Number of subjects for this age range: 44 F.1.2 Adults (18‐64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range SECONDARY OUTCOME: Secondary end point(s): Change in:; ‐ Body composition; ‐ Quality of life; ‐ Hyperphagia questionnaire; ‐ Theory of Mind test; ‐ Diary concerning social and food related behaviour; ‐ fMRI (>6 years old); ‐ Laboratory parameters ; ‐ Safety parameters Timepoint(s) of evaluation of this end point: Studygroup 1: ; Day 1: baseline assessments in the hospital, first administration of oxytocin followed by observation period and instruction of administration; Day 2‐month 6: administration of oxytocin one/twice a day every day at home; ‐ 6 months: hospital visit and assessments as mentioned on day 1; ‐ Mont 6‐month 7: wash‐out period; ‐ 7 months: parents fill out a questionnaire at home. Start other dosing regimen. ; Month 7‐month 13: administration of oxytocin once/twice daily every day at home; 13 months: hospital visit and assessment as mentioned on day 1; ; For studygroup 2 assessments will be done on day 1 (hospital), at 3 months (hospital), at 4 months (questionnaire at home), 7 months (hospital);