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Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial (RUBIVAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01619644
Recruitment Status : Completed
First Posted : June 14, 2012
Last Update Posted : March 18, 2015
Fondation Syndrome de Rubinstein-Taybi
Information provided by (Responsible Party):
University Hospital, Bordeaux

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).

Condition or disease Intervention/treatment Phase
Rubinstein-Taybi Syndrome Drug: sodium valproate Drug: Placebo Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial
Study Start Date : April 2012
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014

Arm Intervention/treatment
Experimental: Sodium Valproate
Group of 40 patients receiving one year of sodium valproate
Drug: sodium valproate
sodium valproate (HDAC inhibitor) with an oral dosage of 30 mg/kg/jour

Placebo Comparator: Placebo
Group of 20 patients receiving one year of placebo
Drug: Placebo
Placebo with an oral dosage of 30 mg/kg/jour

Primary Outcome Measures :
  1. Memory tests (assessing memory learning) [ Time Frame: 1 year ]

    The main outcome measure was to evaluate long term memory with two subtests :

    • point location, subtest of CMS (children memory scale). The score ranges from 0 to 6
    • image recognition, subtest of RBMT (Rivermead Behavioural Memory Test). The score range from 0 to 10. One point for each image recognized A patient is said to be responder if after one year of treatment , his or her test result increase for one point at least one of the two tests

Secondary Outcome Measures :
  1. Special brain imaging profile and motor skills (posturology and motor coordination in a visio-manual pointing task) [ Time Frame: 1 year ]

    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

  2. Cognitive and developmental profile [ Time Frame: 1 year ]
    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

  3. Histone acetylation profile [ Time Frame: 1 year ]
  4. Global acetylation level [ Time Frame: 1 year ]
  5. Acetylation level of selected gene [ Time Frame: 1 year ]
  6. Measurement of selected gene expression [ Time Frame: 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01619644

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University Hospital Bordeaux, France
Bordeaux, France, 33076
Sponsors and Collaborators
University Hospital, Bordeaux
Fondation Syndrome de Rubinstein-Taybi
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Principal Investigator: Didier LACOMBE, PU-PH University Hospital Bordeaux, France
Study Chair: Paul PEREZ, PH University Hospital Bordeaux, France
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Responsible Party: University Hospital, Bordeaux Identifier: NCT01619644    
Other Study ID Numbers: CHUBX 2011/20
First Posted: June 14, 2012    Key Record Dates
Last Update Posted: March 18, 2015
Last Verified: March 2015
Keywords provided by University Hospital, Bordeaux:
Rubinstein Taybi
explorative phase 2
clinical approach
biological approach
motor skills
Additional relevant MeSH terms:
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Rubinstein-Taybi Syndrome
Hand Deformities, Congenital
Craniofacial Abnormalities
Pathologic Processes
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Musculoskeletal Abnormalities
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Hand Deformities
Upper Extremity Deformities, Congenital
Limb Deformities, Congenital
Valproic Acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs