E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prader Willi Syndrom |
Syndrome de Prader-Willi |
|
E.1.1.1 | Medical condition in easily understood language |
Prader Willi Syndrom |
Syndrome de Prader-Willi |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036476 |
E.1.2 | Term | Prader-Willi syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To study tolerance oxytocin repeated nasal administrations during 7 days (according to 3 plans of administration) to babies with Prader Willi Syndrom younger than 5 months. |
Etudier la tolérance d’administrations intranasales répétées d’OT pendant 7 jours selon 3 schémas d’administration chez des nourrissons présentant un SPW âgés de moins de 5 mois. |
|
E.2.2 | Secondary objectives of the trial |
• Preliminary study of efficacy on:
• suckling and swallowing and quantity of milk intake/day
• infant-mother interactions before during and after feeding
• weight gain and growth
• Pathophysiological study of
• cerebral metabolism (fMRI bold)
• plasma levels of ghrelin and other peptides involved in feeding behaviour or energy metabolism • Pharmacokinetic study “à minima”: measurement of circulating oxytocin levels before administration and every 48hrs.
|
o réaliser une étude préliminaire d’efficacité sur:
- la succion/déglutition et la prise alimentaire
- les interactions mère-nourrisson avant, pendant et après la tétée
- l’évolution staturopondérale
o réaliser une étude physiopathologique de l’effet de l’OT:
- sur le métabolisme cérébral
- sur les taux circulants de ghreline et de certains peptides et neuropeptides impliqués dans la régulation de l’appétit
o réaliser une étude de pharmacocinétique à minima : mesure des taux circulants d’OT avant et sous traitement
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Infants with PWS genetically confirmed
Aged less than 5 months
|
Enfant de moins de 5 ans Diagnostic SPW confirmé génétiquement
|
|
E.4 | Principal exclusion criteria |
Infants presenting hepatic insufficiency
Infants presenting renal insufficiency
Infants with abnormal ECG
|
Insuffisance hépatique
Insuffisance rénale
ECG anormal (allongement intervalle QT) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Occurrence of adverse event, description and quantification of their severity, imputability to repeated intranasal administration of OT |
surveillance de l’apparition d’effets indésirables systémiques, évaluation de l’imputabilité de l'admninistration intranasale de l’OT pendant 7 jours |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
during 7 days. |
pendant 7 jours |
|
E.5.2 | Secondary end point(s) |
Preliminary study of efficacy on:
Suckling and swallowing and quantity of milk intake/day
Infant-mother interactions before during and after feeding
weight gain and growth
Pathophysiological study of
cerebral metabolism (fMRI bold)
plasma levels of ghrelin and other peptides involved in feeding behaviour or energy metabolism
Pharmacokinetic study “à minima”: measurement of circulating oxytocin levels before administration and every 48hrs. |
- Evaluation de la succion/déglutition :
o à l’aide d’une grille (Annexe 4) établie par notre équipe multidisciplinaire à partir de différentes échelles validées
o nombre de prise de biberons sur 24 heures, quantité de lait prise à chaque biberon, durée des tétées, efficience de la prise pour 2 tétées/ 24h (quantité de lait prise sur les 5 premières minutes de la tétée)
o par radioscopie avant et 7 jours après la première administration.
- Evaluation des interactions Mère-Nourrissons avant, pendant et après la tétée selon une grille (Annexe 4) avant, 3 jours et 7 jours après la première administration
- Evaluation staturo-pondérale : poids tous les jours, taille à l’inclusion et à la sortie de l’étude
- Métabolisme cérébral : une IRM fonctionnelle de repos (rs-IRMf pour resting state IRM) sera faite avant et 7 jours après la première administration.
- Dosages sanguins de l’OT, de la ghreline et de certains peptides et neuropeptides impliqués dans la régulation de l’appétit (leptine, cortisol, insuline, GLP-1, PYY, polypeptide pancréatique, orexine A, MSH) avant, 3 jours et 7 jours après la première administration
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|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Before and during 7 days after OT admininistration. |
Avant et pendant 7 jours après l'administration d'ocytocine. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
3 paliers dose croissante |
3 modalities |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the trial is the last visit of last subject but if 2 serious adverse events, study will be stopped. |
Dernière visite du dernier patient sauf si 2 EIGs, l'étude sera stoppée. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |