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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Fondation Syndrome de Rubinstein-Taybi
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT01619644
First received: June 12, 2012
Last updated: April 1, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Rubinstein-Taybi Syndrome
Drug: sodium valproate
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • Memory tests (assessing memory learning) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    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:
  • Special brain imaging profile and motor skills (posturology and motor coordination in a visio-manual pointing task) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    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


  • Cognitive and developmental profile [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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

  • Histone acetylation profile [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Global acetylation level [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Acetylation level of selected gene [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Measurement of selected gene expression [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: April 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   6 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01619644

Locations
France
University Hospital Bordeaux, France
Bordeaux, France, 33076
Sponsors and Collaborators
University Hospital, Bordeaux
Fondation Syndrome de Rubinstein-Taybi
Investigators
Principal Investigator: Didier LACOMBE, PU-PH University Hospital Bordeaux, France
Study Chair: Paul PEREZ, PH University Hospital Bordeaux, France
  More Information

No publications provided

Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT01619644     History of Changes
Other Study ID Numbers: CHUBX 2011/20
Study First Received: June 12, 2012
Last Updated: April 1, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
RTS
Rubinstein Taybi
explorative phase 2
clinical approach
biological approach
motor skills

Additional relevant MeSH terms:
Rubinstein-Taybi Syndrome
Syndrome
Hand Deformities, Congenital
Osteochondrodysplasias
Craniofacial Abnormalities
Disease
Pathologic Processes
Dysostoses
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
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014