X-linked Mental Retardation Clinical Trial
— XLMROfficial title:
Clinical Phenotyping and Characterization of Neural Networks and Cognitive Processes Involved in Mental Retardation X-linked
X-linked Mental retardation (XLMR) represent 10% of the causes of mental retardation with a
prevalence in both sexes around 1/296, i.e. 3.3 / 1000 births (Opitz et al., 1986). This
heterogeneous group of XLMR includes dozens of rare diseases, some of them affecting only a
few patients. Molecular diagnosis is currently available in France for 25 XLMR genes, within
the national network of XLMR molecular diagnosis. However, whereas some syndromes such as
Fragile X syndrome, are now well clinically defined, this is not the case for recently
identified syndromes for which very few data is available, preventing clinicians to focus
molecular diagnosis on a specific gene.
Therefore, this study aims to :
- Achieve a description of the clinical phenotype specific to each XLMR gene (Phase 1 of
the study, n=200)
- Characterize the cognitive learning mechanisms and dysfunctional neural networks
involved (Phase 2 of the study, n=75, i.e. 5 groups of 15 patients with a mutation in
the same gene). These two elements constitute key steps to develop appropriate
rehabilitation strategies and targeted pharmacological therapies.
Moreover, the impact of mental retardation on the primary caregiver within the family and the
induced burden in terms of psycho-social, organizational and economic burden will also be
assessed. These elements, directly related to the patient's environment, are very important
to characterize in order to better understand the consequences of each gene mutation (Phase 3
of the study, n=283). For example, it is necessary to better understand the impact of Fragile
X syndrome in terms of capacity and behavior, lifestyle, and health care needs of the
patients While advancing knowledge allows to consider innovative therapeutics, the
implementation of these therapeutics and assessment of their impact on the patients' life
trajectory, require precise characterization of the population to be treated in medico
socioeconomic terms.
| Status | Recruiting |
| Enrollment | 573 |
| Est. completion date | March 31, 2018 |
| Est. primary completion date | December 2015 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 2 Years to 60 Years |
| Eligibility |
Inclusion Criteria: - Age : from 2 to 60 years old - Having a pathogenic mutation of one of the X chromosome genes associated with : - For boys : mental retardation (IQ<70), and/or developmental delay (DQ<70) and/or pervasive developmental disorder (autism, Asperger…) - For girls : mental retardation (IQ<70), and/or developmental delay (DQ<70) and/or pervasive developmental disorder (autism, Asperger…) and/or specific learning disabilities Exclusion Criteria: - patient or parents refusal to participate in the study - genetic polymorphism in a X chromosome gene involved in mental retardation but not considered as pathogenic - person refusing to be informed if an abnormality would be discovered during medical examination |
| Country | Name | City | State |
|---|---|---|---|
| France | Groupement Hospitalier Est - Hôpital Femme Mère Enfant - Service de neurologie pédiatrique | Bron |
| Lead Sponsor | Collaborator |
|---|---|
| Hospices Civils de Lyon |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Clinical phenotyping of neurodevelopment: acquisition age of early developmental skills (motor and language), and the adaptive skills profile (Vineland adaptive behavioral scale) | The primary outcome measure is composite and includes acquisition age of early developmental skills (motor and language), and the adaptive skills profile (Vineland adaptive behavioral scale). The Vineland adaptive behavioral scale performed during a semi-structured interview of the parents of the patient, will assess the adaptive behavior profile of the patient (including communication, daily living skills, socialization, motricity and the global adaptive score). | at inclusion (Day 1) | |
| Secondary | Intellectual functioning assessment (Wechsler scale) | The Intellectual Quotient of the patient will be assessed using a Wechsler scale, adapted to the age of the patient. For patients younger than 3 years or too severely impaired to perform a Wechsler scale, the Brunet Lézine scale will be used. | at inclusion (Day 1) | |
| Secondary | Raven's Progressive matrices | The Raven's Progressives matrices test will allow to assess the non-verbal reasoning mental age of the patient | at inclusion (Day 1) | |
| Secondary | Peabody Picture Vocabulary Test Revised | The Peabody Picture Vocabulary Test Revised will allow to determine the Vocabulary age (receptive language) of the patient. | at inclusion (Day 1) | |
| Secondary | Edinburgh handedness test | The Edinburgh handedness test will assess the handedness of the patients. | at inclusion (Day 1) | |
| Secondary | Birth parameters: weight, height and head circumference and APGAR score | The birth parameters include weight, height and head circumference at birth, as well as the initial cardiac and pulmonary adaptation (APGAR score). | at inclusion (Day 1) | |
| Secondary | Nisonger child behavior rating form | The Nisonger child behavior rating form will allow the assessment of behavior disorders including: conduct disorders, anxiety, hyperactivity, automutilation/stereotyped behavior, self-isolation/rituals, sensitivity/susceptibility. | at inclusion (Day 1) | |
| Secondary | Caregiver Burden Inventory Modified | The Caregiver Burden Inventory Modified will allow the assessment of the impact of mental retardation on the primary caregiver within the family. | at inclusion (Day 1) | |
| Secondary | Analogical visual reasoning task (behavior assessment) | This paradigm (HCL/CNRS patented), appropriate for mentally retarded patients provides an objective and quantitative assessment of visual analogical reasoning and cognitive inhibition. | at inclusion (Day 1) | |
| Secondary | Analogical visual reasoning task (eye-tracking assessment) | The eye-tracking analysis of this paradigm (HCL/CNRS patented) made it possible to identify the strategy used by participants to solve the task. Mentally Retarded patients are not able to explicitly explain the strategy they used to solve the task, but with eye-tracking analysis, we can understand how they performed the task, which is crucial information in order to help them improve their performance through remediation strategies. | at inclusion (Day 1) | |
| Secondary | Kinematic analysis of a grasping movement | This kinematic analysis of a grasping movement will allow us to study the effect of the orientation (+56°or -56°) and the type of pinch (thumb-index, thumb-middle finger and thumb-annular) on the movement duration and both the transport component (wrist acceleration and velocity peaks, latencies and amplitudes) and the grasp component (maximum grip aperture latency and amplitude and opposition axis). | at inclusion (Day 1) | |
| Secondary | Structural neuroimaging by MRI | Structural brain MRI analysis will determine if a specific morphological neuroanatomical pattern can be found for each X-linked mental retardation gene. | at inclusion (Day 1) | |
| Secondary | Functional neuroimaging by MRI | Functional brain MRI analysis will determine if patients with X-linked mental retardation have a specific functional neuroanatomical pattern associated to the reasoning task. | at inclusion (Day 1) | |
| Secondary | School curriculum: age and type of shool | The school curriculum will include the age at school entrance, and the type of school the child went to. | at inclusion (Day 1) |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Terminated |
NCT00916903 -
Genetic Disease Gene Identification
|