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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-003784-30 | EudraCT Number |
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| Name | Class |
|---|---|
| Fondation Syndrome de Rubinstein-Taybi | UNKNOWN |
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An exploratory phase 2 therapeutic trial in children from 6 to 21, RTS carriers, randomized to be treated either with sodium valproate with the usual pediatric dosage (30 mg/kg/j), or by placebo for one year.
The investigator would like to include children because they could best profit from it due to their neuronal plasticity as CBP and EP300 take effect through neuronal and synaptic plasticity.
The therapeutic effect of sodium valproate in RTS patients will be assessed thanks to a clinical approach (learning and memory neuropsychological evaluation, fine motor skills assessment by pointing), to a biological approach (histone acetylation functional tests), and to imaging (morphological and functional MRI).
Such a multidisciplinary approach has never been presented for this syndrome; it should enable us identifying specific cognitive and motor deficits and their association thanks to imaging markers. Assessing the various aspects of motor skills, i.e. primary (movements, standing at ease position, immobility) and complex motor skills (actions and behaviours, motor aspects of feelings and language expressions) is an integral part of the clinical examination in psychiatrics.
The main interest of a functional capacity analysis is to be used as an index allowing the assessment of the nervous system's global capacities and the study of the connections between cognitive functions and motor skills Main objective: 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".
Double-blind phase 2 clinical trial, designed as a one-step Fleming design but with a control group. Rubival is a two-parallel group randomized trial:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sodium Valproate | Experimental | Group of 40 patients receiving one year of sodium valproate |
|
| Placebo | Placebo Comparator | Group of 20 patients receiving one year of placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sodium valproate | Drug | sodium valproate (HDAC inhibitor) with an oral dosage of 30 mg/kg/jour |
|
| Measure | Description | Time Frame |
|---|---|---|
| Memory tests (assessing memory learning) | The main outcome measure was to evaluate long term memory with two subtests :
| 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Special brain imaging profile and motor skills (posturology and motor coordination in a visio-manual pointing task) | For motor skills, the profile was based on 3 tasks : posturology, motor coordination in a visuo-manual pointing task and in mobile interception task.. For brain imaging, a variety of outcome measures will be used for example, brain volume, anisotropy fraction, diffusion coefficient for structural magnetic imaging and the signal intensity for functional Magnetic Resonance Imaging |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Didier LACOMBE, PU-PH | University Hospital Bordeaux, France | Principal Investigator |
| Paul PEREZ, PH | University Hospital Bordeaux, France | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Bordeaux, France | Bordeaux | 33076 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 14974086 | Background | Coupry I, Monnet L, Attia AA, Taine L, Lacombe D, Arveiler B. Analysis of CBP (CREBBP) gene deletions in Rubinstein-Taybi syndrome patients using real-time quantitative PCR. Hum Mutat. 2004 Mar;23(3):278-84. doi: 10.1002/humu.20001. | |
| 28748333 | Result | Cazalets JR, Bestaven E, Doat E, Baudier MP, Gallot C, Amestoy A, Bouvard M, Guillaud E, Guillain I, Grech E, Van-Gils J, Fergelot P, Fraisse S, Taupiac E, Arveiler B, Lacombe D. Evaluation of Motor Skills in Children with Rubinstein-Taybi Syndrome. J Autism Dev Disord. 2017 Nov;47(11):3321-3332. doi: 10.1007/s10803-017-3259-1. |
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| ID | Term |
|---|---|
| D012415 | Rubinstein-Taybi Syndrome |
| ID | Term |
|---|---|
| D004413 | Dysostoses |
| D001848 | Bone Diseases, Developmental |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| D014635 | Valproic Acid |
| ID | Term |
|---|---|
| D010421 | Pentanoic Acids |
| D014631 | Valerates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
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| Placebo | Drug | Placebo with an oral dosage of 30 mg/kg/jour |
|
| 1 year |
| Cognitive and developmental profile | Based on the results of several battery test and evaluation scale, VABS II (Vineland Adaptative Behaviour Scale II), Leiter R, EVIP, ECOSSE, NEPSY : fluency verbal sutest, CMS : 2 subtests, RBMT : 1 subtest | 1 year |
| Histone acetylation profile | 1 year |
| Global acetylation level | 1 year |
| Acetylation level of selected gene | 1 year |
| Measurement of selected gene expression | 1 year |
| D019465 |
| Craniofacial Abnormalities |
| D009139 | Musculoskeletal Abnormalities |
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D025063 | Chromosome Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009930 |
| Organic Chemicals |
| D005232 | Fatty Acids, Volatile |
| D005227 | Fatty Acids |
| D008055 | Lipids |