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

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).

Study Overview

• Status: Completed
• Conditions: Rubinstein-Taybi Syndrome
• Intervention / Treatment: Drug: sodium valproate; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • University Hospital Bordeaux, France

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	1 year
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	1 year
Histone acetylation profile		1 year
Global acetylation level		1 year
Acetylation level of selected gene		1 year
Measurement of selected gene expression		1 year

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Collaborators: 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

Publications and helpful links

General Publications

• Cazalets JR, Bestaven E, Doat E, Baudier MP, Gallot C, Amestoy A, Bouvard M, Guillaud E, Guillain I, Grech E, Van-Gils J, Fergelot P, Fraisse S, Taupiac E, Arveiler B, Lacombe D. Evaluation of Motor Skills in Children with Rubinstein-Taybi Syndrome. J Autism Dev Disord. 2017 Nov;47(11):3321-3332. doi: 10.1007/s10803-017-3259-1.
• Coupry I, Monnet L, Attia AA, Taine L, Lacombe D, Arveiler B. Analysis of CBP (CREBBP) gene deletions in Rubinstein-Taybi syndrome patients using real-time quantitative PCR. Hum Mutat. 2004 Mar;23(3):278-84. doi: 10.1002/humu.20001.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: June 12, 2012
• First Submitted That Met QC Criteria: June 12, 2012
• First Posted (Estimated): June 14, 2012

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: motor skills; RTS; Rubinstein Taybi; explorative phase 2; clinical approach; biological approach
• Additional Relevant MeSH Terms: Neurologic Manifestations; Bone Diseases; Musculoskeletal Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Neurobehavioral Manifestations; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Congenital Abnormalities; Abnormalities, Multiple; Intellectual Disability; Chromosome Disorders; Bone Diseases, Developmental; Dysostoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Rubinstein-Taybi Syndrome; Organic Chemicals; Fatty Acids; Lipids; Acids, Acyclic; Carboxylic Acids; Pentanoic Acids; Valerates; Fatty Acids, Volatile; Valproic Acid
• Other Study ID Numbers: CHUBX 2011/20; 2011-003784-30 (EudraCT Number)