Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial (RUBIVAL)
Primary Purpose
Rubinstein-Taybi Syndrome
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
sodium valproate
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rubinstein-Taybi Syndrome focused on measuring RTS, Rubinstein Taybi, explorative phase 2, clinical approach, biological approach, motor skills
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
Sites / Locations
- University Hospital Bordeaux, France
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Sodium Valproate
Placebo
Arm Description
Group of 40 patients receiving one year of sodium valproate
Group of 20 patients receiving one year of placebo
Outcomes
Primary Outcome Measures
Memory tests (assessing memory learning)
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)
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
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
Global acetylation level
Acetylation level of selected gene
Measurement of selected gene expression
Full Information
NCT ID
NCT01619644
First Posted
June 12, 2012
Last Updated
March 17, 2015
Sponsor
University Hospital, Bordeaux
Collaborators
Fondation Syndrome de Rubinstein-Taybi
1. Study Identification
Unique Protocol Identification Number
NCT01619644
Brief Title
Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial
Acronym
RUBIVAL
Official Title
Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial
Study Type
Interventional
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Bordeaux
Collaborators
Fondation Syndrome de Rubinstein-Taybi
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rubinstein-Taybi Syndrome
Keywords
RTS, Rubinstein Taybi, explorative phase 2, clinical approach, biological approach, motor skills
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sodium Valproate
Arm Type
Experimental
Arm Description
Group of 40 patients receiving one year of sodium valproate
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Group of 20 patients receiving one year of placebo
Intervention Type
Drug
Intervention Name(s)
sodium valproate
Intervention Description
sodium valproate (HDAC inhibitor) with an oral dosage of 30 mg/kg/jour
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo with an oral dosage of 30 mg/kg/jour
Primary Outcome Measure Information:
Title
Memory tests (assessing memory learning)
Description
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
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Special brain imaging profile and motor skills (posturology and motor coordination in a visio-manual pointing task)
Description
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
Time Frame
1 year
Title
Cognitive and developmental profile
Description
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
Time Frame
1 year
Title
Histone acetylation profile
Time Frame
1 year
Title
Global acetylation level
Time Frame
1 year
Title
Acetylation level of selected gene
Time Frame
1 year
Title
Measurement of selected gene expression
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Didier LACOMBE, PU-PH
Organizational Affiliation
University Hospital Bordeaux, France
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Paul PEREZ, PH
Organizational Affiliation
University Hospital Bordeaux, France
Official's Role
Study Chair
Facility Information:
Facility Name
University Hospital Bordeaux, France
City
Bordeaux
ZIP/Postal Code
33076
Country
France
12. IPD Sharing Statement
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Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial
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