Prader-Willi Syndrome
Conditions
Keywords
Prader-Willi syndrome, Oxytocin, Behavioural troubles
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.
Detailed description
Two groups of patients will be constituted according to their age; Group 1 children aged from 3 to 6 years (n = 20) and Group 2 children aged from 7 to 12 years (n = 20). Within each group, subjects will be randomized to receive either oxytocin or placebo for 12 consecutive weeks. A second period of 12 consecutive oxytocin treatment weeks will then be performed for all patients, followed by a 4-week observation period to document effects after discontinuation of treatment.
Interventions
DRUGOxytocin
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.
DRUGPlacebo
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.
Sponsors
University Hospital, Toulouse
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
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.
Intervention model description
Children will receive after randomization either placebo or oxytocin administration (daily intranasal) for a total duration of 12 consecutive weeks.
Eligibility
Sex/Gender
ALL
Age
3 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evolution of behavioural troubles evaluated by the global score of Child Behavior Check List Questionnaire after 12 weeks of oxytocin/placebo treatment. | Week 12 | It's variation between inclusion and 12 weeks of total score total problems from the Child Behavior Check List Questionnaire. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of hyperphagia after 12 weeks of oxytocin/placebo treatment. | Week 12 | It is the variation of each of the three sub-scores obtained from the Dykens hyperphagia questionnaire between day 0 and week 12. |
| Evaluation of social skills after 12 weeks of oxytocin/placebo treatment. | Week 12 | It is variation between day 0 and week 12 of the total score obtained from the social skills assessment questionnaire for children aged from 3 to 6 years and the Social Responsiveness Scale questionnaire for children aged from 7 to 12 years. |
| Evaluation of auto- and hetero-aggressive after 12 weeks of oxytocin/placebo treatment. | Week 12 | It is variation between day 0 and week 12 of the total score obtained from the self-aggression assessment questionnaire. |
| Evaluation of attentional abilities after 12 weeks of oxytocin/placebo treatment, for patients aged from 7 to 12 years at inclusion. | Week 12 | It is evolution of attentional abilities is evaluated by a computerized test, the Attention Network Test. |
| Evaluation of global clinical status after 12 weeks of oxytocin/placebo treatment. | Weeks 12 | It is improvement of the patient's overall clinical condition after 12 weeks of treatment with oxytocin/placebo. It's assessed by the Clinical Global Impression Scale's score. This scale of improvement of Clinical Global Impression is a 7-point ordinal qualitative scale of very greatly improved rated + 3 to very strongly aggravated rated -3. The result is expressed in total score which varies from -3 to +3. |
| Evaluation of acyl and desacyl ghrelin plasma levels after 12 weeks of oxytocin/placebo treatment. | Week 12 | It is evolution of circulating levels of acylated and deacylated ghrelin will be the variations of these rates and the variation of the relationships between day 0 and week 12. |
| Evaluation of metabolic brain resting state after 12 weeks of oxytocin/placebo treatment, for patients aged from 7 to 12 years at inclusion. | Week 12 | It is evolution of metabolic brain resting state is evaluated by a magnetic resonance imaging to study the cerebral metabolism between day 0 and week 12. |
| Evaluation of psychopathology after 12 weeks of oxytocin/placebo treatment. | Week 12 | It is the variation of the following sub-scores obtained from the Child Behaviour Check List questionnaire (only the following 3 subscales) between day 0 and week 12. |
Countries
France
Outcome results
None listed