Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial

NCT01619644 | Completed Phase 2 DMC

• 1 other identifier: CHUBX 2011/20
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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).

Conditions

Rubinstein-Taybi Syndrome

Keywords

RTS; Rubinstein Taybi; explorative phase 2; clinical approach; biological approach; motor skills

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Special brain imaging profile and motor skills (posturology and motor coordination in a visio-manual pointing task)

  1 year

• Cognitive and developmental profile

  1 year

• Histone acetylation profile

  1 year

• Global acetylation level

  1 year

• Acetylation level of selected gene

  1 year

Study Arms (2)

Sodium Valproate

EXPERIMENTAL

Group of 40 patients receiving one year of sodium valproate

Drug: sodium valproate

Placebo

PLACEBO COMPARATOR

Group of 20 patients receiving one year of placebo

Drug: Placebo

Interventions

sodium valproate DRUG

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

Sodium Valproate

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 6 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Bordeaux: lead
• Fondation Syndrome de Rubinstein-Taybi: collaborator

Study Sites (1)

University Hospital Bordeaux, France

Bordeaux, 33076, France

Location

MeSH Terms

Conditions

Rubinstein-Taybi Syndrome

Interventions

Valproic Acid

Condition Hierarchy (Ancestors)

Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Didier LACOMBE, PU-PH

  University Hospital Bordeaux, France

  PRINCIPAL INVESTIGATOR

• Paul PEREZ, PH

  University Hospital Bordeaux, France

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2012
• First Posted: June 14, 2012
• Study Start: April 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: March 18, 2015

Record last verified: 2015-03

Locations

FR (1)