Clinical Trial Results:
Effects of intranasal administrations of oxytocin on beahvioural troubles, hyperphagia and social skills in children with Prader-Willi syndrome aged from 3 to 12 years.
Summary
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EudraCT number |
2016-003273-18 |
Trial protocol |
FR |
Global end of trial date |
11 Jan 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Jun 2024
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First version publication date |
14 Jun 2024
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
RC31-15-7837
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03114371 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
CHU de Toulouse
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Sponsor organisation address |
2 rue de Viguerie, Toulouse, France, 31059
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Public contact |
Nadège ALGANS, University Hospital of Toulouse, +33 0561777204, algans.n@chu-toulouse.fr
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Scientific contact |
Dr Sophie Cabal-Berthoumieu, University Hospital of Toulouse, +33 05 34 55 74 32 , cabal-berthoumieu.s@chu-toulouse.fr
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
11 Jan 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 Jan 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Jan 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Study the effect of the administration intranasale of oxytocin (OXT) during 12 weeks on the behavior disorders by comparison with a placebo
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Protection of trial subjects |
An Independent Monitoring Committee (IMC) was formed to review the study data and to assess the safety of the OXYJEUNE study based on Serious and Non-Serious Events, in particular their potential relationship to the investigational drug.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Nov 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 40
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Worldwide total number of subjects |
40
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EEA total number of subjects |
40
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
35
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Adolescents (12-17 years) |
5
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients with Prader-Willi Syndrome will be recruited by the PWS Reference Center of the Toulouse University Hospital from the active file of patients followed. | |||||||||||||||
Pre-assignment
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Screening details |
Patients with PWS aged from 3 to 12 years | |||||||||||||||
Period 1
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Period 1 title |
Baseline
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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OXYTOCIN | |||||||||||||||
Arm description |
Daily intranasal administrations of oxytocin for 12 weeks. 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. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Syntocinon PR1
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Investigational medicinal product code |
H01BB02
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Other name |
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Pharmaceutical forms |
Nasal spray
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Routes of administration |
Nasal use
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Dosage and administration details |
The dosage of OXT will be 8 IU for patients aged 3-6 years and 16 IU for patients aged 7-12 years at inclusion.
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Arm title
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PLACEBO | |||||||||||||||
Arm description |
Daily intranasal administrations of placebo for 12 weeks. 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. | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Syntocinon PR1
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Investigational medicinal product code |
H01BB02
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Other name |
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Pharmaceutical forms |
Nasal spray
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Routes of administration |
Nasal use
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Dosage and administration details |
The dosage of OXT will be 8 IU for patients aged 3-6 years and 16 IU for patients aged 7-12 years at inclusion.
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Period 2
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Period 2 title |
OT vs Placebo
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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OXYTOCIN | |||||||||||||||
Arm description |
Oxytocin treatment 8 unit for patients aged from 3 to 6 years and 16 units for patients aged from 7 to 12. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Syntocinon PR1
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Investigational medicinal product code |
H01BB02
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Other name |
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Pharmaceutical forms |
Nasal spray
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Routes of administration |
Nasal use
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Dosage and administration details |
The dosage of OXT will be 8 IU for patients aged 3-6 years and 16 IU for patients aged 7-12 years at inclusion.
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Arm title
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Placebo | |||||||||||||||
Arm description |
2 spray for patients aged from 3 to 6 years 4 spray for patients aged from 7 to 12 years | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal spray, solution
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Routes of administration |
Nasal use
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Dosage and administration details |
2 spray for patients aged from 3 to 6 years
4 spray for patients aged from 7 to 12 years
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Period 3
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Period 3 title |
open label period
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Arm title
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Oxytocin | |||||||||||||||
Arm description |
8 UI (2 spray) for patients aged from 3 to 6 years 16 UI (4 spray) for patients aged from 7 to 12 years | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Syntocinon
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Investigational medicinal product code |
HB01BB02
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Other name |
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Pharmaceutical forms |
Nasal spray, solution
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Routes of administration |
Nasal use
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Dosage and administration details |
8 UI (2 spray) for patients aged from 3 to 6 years
16 UI (4 spray) for patients aged from 3 to 6 years
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Baseline characteristics reporting groups
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Reporting group title |
OXYTOCIN
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Reporting group description |
Daily intranasal administrations of oxytocin for 12 weeks. 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PLACEBO
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Reporting group description |
Daily intranasal administrations of placebo for 12 weeks. 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
OXYTOCIN
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Reporting group description |
Daily intranasal administrations of oxytocin for 12 weeks. 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. | ||
Reporting group title |
PLACEBO
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Reporting group description |
Daily intranasal administrations of placebo for 12 weeks. 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. | ||
Reporting group title |
OXYTOCIN
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Reporting group description |
Oxytocin treatment 8 unit for patients aged from 3 to 6 years and 16 units for patients aged from 7 to 12. | ||
Reporting group title |
Placebo
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Reporting group description |
2 spray for patients aged from 3 to 6 years 4 spray for patients aged from 7 to 12 years | ||
Reporting group title |
Oxytocin
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Reporting group description |
8 UI (2 spray) for patients aged from 3 to 6 years 16 UI (4 spray) for patients aged from 7 to 12 years |
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End point title |
Behavioural troubles (Child Behavior Check List Questionnaire) | |||||||||
End point description |
Change from baseline at week 12 of CBCL Total problems T score
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End point type |
Primary
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End point timeframe |
week 12
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Statistical analysis title |
Total problems score | |||||||||
Statistical analysis description |
Change from baseline at Week 12 in Total Problems score
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Comparison groups |
OXYTOCIN v PLACEBO
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Number of subjects included in analysis |
39
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
< 0.05 | |||||||||
Method |
ANCOVA | |||||||||
Confidence interval |
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End point title |
Hyperphagia | |||||||||
End point description |
Responder analysis on the global score of Dykens Hyperphagia questionnaire: among the patients who had an abnormal score at baseline, number of patients with normal score at week 12
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End point type |
Secondary
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End point timeframe |
week 12
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No statistical analyses for this end point |
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End point title |
Social skills | |||||||||
End point description |
Responder analysis on social skills after 12 weeks of oxytocin/placebo treatment: the social skills were assessed by the PSA questionnaire in children aged from 3 to 6 years and by the SRS questionnaire for children aged from 7 to 12 years.Among the patients who had an abnormal score at baseline, number of patients with normal score at week 12
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End point type |
Secondary
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End point timeframe |
week 12
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No statistical analyses for this end point |
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End point title |
Evaluation of auto- and hetero-aggressive behaviour | |||||||||
End point description |
Responder analysis on ECAA questionnaire item 5 after 12 weeks of oxytocin/placebo treatment: among the patients who had an abnormal score at baseline, number of patients with normal score at week 12
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End point type |
Secondary
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End point timeframe |
week 12
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No statistical analyses for this end point |
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End point title |
the effect of oxytocin (OXT) vs. placebo on psychopathology | |||
End point description |
Different scores are obtained: T scores from 50 to 64 are normal; T scores from 65 to 69 are borderline; beyond 69, we are in the pathological.
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End point type |
Secondary
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End point timeframe |
Evaluation based on the variation of each of the sub-scores obtained on the CBCL questionnaire between J0 and S12.
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No statistical analyses for this end point |
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End point title |
Evaluation of Global Clinical Status After 12 Weeks of Oxytocin/Placebo Treatment | |||||||||
End point description |
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.
responder analysis: responders were defined as patients with a score of +1, +2 or +3
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End point type |
Secondary
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End point timeframe |
week 12
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No statistical analyses for this end point |
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End point title |
Evaluation of acyl and desacyl ghrelin plasma levels after 12 weeks of oxytocin/placebo treatment | |||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
beetween day 0 and week 12
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
The adverse events (serious or not) are reported during all the study.
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
oxytocin group
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Reporting group description |
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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo group
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Reporting group description |
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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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13 Apr 2017 |
The method of randomization has changed:
- Patients now have a unique subject number that will correspond to the sequence number and then the first letter of the last and first names.
- The pre-selection visit has been modified: the investigating physician is responsible for obtaining the signed informed consent form.
- Change in sampling times and the timing of the ECG was requested in order to avoid duplication of blood sampling and to simplify patient management.
- The addition of the appendix 11 corresponding to the grid the global evolution of the patient in the different times between D0 and S12 and between J0 and S24. |
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23 Apr 2018 |
Modification of a secondary endpoint for the analysis of data from the Dykens Questionnaire; modification of a secondary endpoint for the assessment of the evolution of the patient's clinical condition; extension of the duration of inclusions; modification of the dosage of oxytocin treatment |
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26 Nov 2018 |
Addition of an Independent Monitoring Committee (IMC). |
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11 Jan 2019 |
- Collaboration with CROs for statistical analysis design (Excelsus) and statistical analysis (Atlanstat).
- Modification of secondary objectives: Circulating levels of OXT are measured to verify whether OXT accumulates or remains stable as a function of administered doses.
- Modification of primary endpoint: Some children changed age groups during the study, so the questionnaire used is clarified. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
NA |