E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rubinstein-Taybi Syndrome |
Syndrome de Rubinstein-Taybi |
|
E.1.1.1 | Medical condition in easily understood language |
Rubinstein-Taybi Syndrome |
Syndrome de Rubinstein-Taybi |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039281 |
E.1.2 | Term | Rubinstein-Taybi 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 |
Evaluate long term memory with subtest “point location” – CMS and “image recognition” RBMT A patient is said to be responder if after one year his or her test result increase for one point at least one of the two tests : a increase of one point to “point location” or “image recognition”. |
Estimer l’efficacité clinique, après un an de traitement par le valproate de sodium (30mg/kg/j), sur l’évolution de la mémoire à long terme chez des enfants atteint de SRT. |
|
E.2.2 | Secondary objectives of the trial |
Evaluate the impact after one year of treatment with sodium valproate through: - a special brain imaging profile and motor skills (posturology and motor coordination in a visuo-manual pointing task) - cognitive and developmental profile - histone acetylation profile
|
Estimer l’effet après un an de traitement par le valproate de sodium, par: - Un profil particulier en imagerie cérébrale et la motricité (posturologie, et coordination motrice dans une tache de pointage visio-manuel, et une tâche d’interception d’un mobile) - le profil cognitif et développemental - le profil d’acétylation des histones
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Children over 6 and under 21 - RTS confirmed by a genetic study with a CBP gene or EP300 gene mutation - Sufficient cognitive capacities for neuropsychological evaluation - Free and informed consent of the parents or guardians - Children affiliated to or benefiting of the French social welfare system |
- Enfant de plus de 6 ans et de moins de 21 ans - SRT confirmé par étude génétique avec mutation du gène CREBBP ou du gène EP300 - Capacités cognitives permettant l’évaluation neuropsychologique - Consentement libre et éclairé des titulaires de l’autorité parentale - Enfant affilié ou ayant droit au régime de sécurité sociale
|
|
E.4 | Principal exclusion criteria |
- Contraindication to sodium valproate - Women of reproductive age without contraception means - Case history of sodium valproate treatment - Monotherapy treatment for epilepsy with Lamictal with a dosage superior to 5 mg/kg/j - Pregnancy - breastfeeding - renal failure - enzymatic deficit of urea cycle |
- Contre-indication au valproate de sodium - Femme en âge de procréer sans moyen de contraception efficace (oestroprogestatif, dispositif intrautérin) - ATCD de traitement par valproate de sodium - Epilepsie traitée par Lamictal en monothérapie à une posologie supérieure à 5 mg/kg/j - Antécédent familial d’hépatite sévère notamment médicamenteuse - Hépatite aiguë ou chronique. - Femme enceinte. - Allaitement - Insuffisance rénale - Déficit enzymatique du cycle de l’urée |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Memory tests (assessing memory learning) A patient is said to be responder if after one year his or her test result increase for one point at least one of the two tests : a increase of one point to “point location” or “image recognition”.
|
Evaluation de la mémoire à long terme par le subtest « localisation des points » du CMS et « reconnaissance d’images » du RBMT. Le subtest localisation de point est noté sur 6. Le subtest « reconnaissance d’images » du RBMT est noté sur 10. Les patients répondeurs sont définis comme ceux montrant une amélioration de la mémoire à long terme cliniquement considérée comme pertinente, c'est-à-dire se traduisant par une amélioration de 1 point au moins à l’un des 2 tests : épreuves de Localisation des points – CMS ou de Reconnaissance d’images – RBMT (1 point si + 1 image quand < 5 image reconnu à V0 ; + 20% quand >5 images reconnus à V0). Les critères d’efficacité retenus sont ceux évalués à 12 mois de traitement |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Special brain imaging profile and motor skills (posturology and motor coordination in a visuo-manual pointing task) - Cognitive and developmental profile - Histone acetylation profile
|
- Profil particulier en imagerie cérébrale et motricité (posturologie, et coordination motrice dans une tache de pointage visio-manuel) - Profil cognitif et développemental - Profil d’acétylation des histones
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
E.6.4 | Safety | No |
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 | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | Yes |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |