Clinical trial NCT01619644: Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial
Official title: Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rubinstein-Taybi Syndrome
Keywords: RTS
Rubinstein Taybi
explorative phase 2
clinical approach
biological approach
motor skills
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: Fondation Syndrome de Rubinstein-Taybi
First posted: 2012-06-14
Enrollment: 41
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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:

* a placebo group of 20 patients
* a group of 40 patients taking sodium valproate (HDAC inhibitor) with an oral dosage of 30 mg/kg/jour

Eligibility criteria: 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

Exclusion Criteria:

* Contraindication to sodium valproate
* Women of reproductive age without effective contraception means
* Case history of sodium valproate treatment
* Monotherapy treatment for epilepsy with Lamictal with a dosage superior to 5 mg/kg/j
* Family history of severe hepatitis including drug
* Acute or chronic hepatitis
* Pregnancy

Primary outcomes:
measure: Memory tests (assessing memory learning)
timeFrame: 1 year
Secondary outcomes:
measure: Special brain imaging profile and motor skills (posturology and motor coordination in a visio-manual pointing task)
timeFrame: 1 year
measure: Cognitive and developmental profile
timeFrame: 1 year
measure: Histone acetylation profile
timeFrame: 1 year
measure: Global acetylation level
timeFrame: 1 year
measure: Acetylation level of selected gene
timeFrame: 1 year
measure: Measurement of selected gene expression
timeFrame: 1 year
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: University Hospital Bordeaux, France
Study officials:
affiliation: University Hospital Bordeaux, France
name: Didier LACOMBE, PU-PH
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Bordeaux, France
name: Paul PEREZ, PH
role: STUDY_CHAIR
References: