Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial

NCT ID: NCT01619644

Last Updated: 2015-03-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2014-09-30

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

Conditions

Rubinstein-Taybi Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sodium Valproate

Group of 40 patients receiving one year of sodium valproate

Group Type: EXPERIMENTAL

sodium valproate

Intervention Type: DRUG

sodium valproate (HDAC inhibitor) with an oral dosage of 30 mg/kg/jour

Placebo

Group of 20 patients receiving one year of placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo with an oral dosage of 30 mg/kg/jour

Interventions

sodium valproate

sodium valproate (HDAC inhibitor) with an oral dosage of 30 mg/kg/jour

Intervention Type: DRUG

Placebo

Placebo with an oral dosage of 30 mg/kg/jour

Intervention Type: DRUG

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondation Syndrome de Rubinstein-Taybi

UNKNOWN

Sponsor Role: collaborator

University Hospital, Bordeaux

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Didier LACOMBE, PU-PH

Role: PRINCIPAL_INVESTIGATOR

University Hospital Bordeaux, France

Paul PEREZ, PH

Role: STUDY_CHAIR

University Hospital Bordeaux, France

Locations

University Hospital Bordeaux, France

Bordeaux, , France

Countries

France

Other Identifiers

CHUBX 2011/20

Identifier Type: -

Identifier Source: org_study_id