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Clinical Phenotyping and Characterization of Neural Networks and Cognitive Processes Involved in Mental Retardation X-linked (XLMR)

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ClinicalTrials.gov Identifier: NCT02854956
Recruitment Status : Recruiting
First Posted : August 4, 2016
Last Update Posted : July 12, 2017
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
X-linked Mental Retardation Behavioral: Neuropsychological, cognitive and behavioral assessment Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 573 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Clinical Phenotyping and Characterization of Neural Networks and Cognitive Processes Involved in Mental Retardation X-linked
Study Start Date : April 2011
Actual Primary Completion Date : December 2015
Estimated Study Completion Date : March 31, 2018


Arm Intervention/treatment
X-linked Mental retardation
This is an observational study which will allow to precisely describe the phenotype associated to each X-linked mental retardation gene.
Behavioral: Neuropsychological, cognitive and behavioral assessment

The assessment includes mainly :

  • The Raven's Progressives matrices test which allow to assess the non-verbal reasoning mental age of the patient
  • The Wechsler scale or Brunet Lézine scale which allow to assess The Intellectual Quotient
  • The Peabody Picture Vocabulary Test Revised which allow to determine the Vocabulary age (receptive language).
  • The Vineland adaptive behavioral scale which allow to assess the adaptive behavior
  • The Nisonger child behavior rating form which allow to assess the behavior disorders
  • Analogical visual reasoning task (eye-tracking assessment and behavior assessment) which allow to identify the strategy used to solve the task and provides an objective and quantitative assessment of visual analogical reasoning and cognitive inhibition.
  • Kinematic analysis of a grasping movement which allow to study the effect of the orientation and the type of pinch on the movement duration and both the transport component and the grasp component.

Control Group
This group will be compared to X-linked mental retardation group in order to obtain a baseline on some cognitive tests.
Behavioral: Neuropsychological, cognitive and behavioral assessment

The assessment includes mainly :

  • The Raven's Progressives matrices test which allow to assess the non-verbal reasoning mental age of the patient
  • The Wechsler scale or Brunet Lézine scale which allow to assess The Intellectual Quotient
  • The Peabody Picture Vocabulary Test Revised which allow to determine the Vocabulary age (receptive language).
  • The Vineland adaptive behavioral scale which allow to assess the adaptive behavior
  • The Nisonger child behavior rating form which allow to assess the behavior disorders
  • Analogical visual reasoning task (eye-tracking assessment and behavior assessment) which allow to identify the strategy used to solve the task and provides an objective and quantitative assessment of visual analogical reasoning and cognitive inhibition.
  • Kinematic analysis of a grasping movement which allow to study the effect of the orientation and the type of pinch on the movement duration and both the transport component and the grasp component.




Primary Outcome Measures :
  1. Clinical phenotyping of neurodevelopment: acquisition age of early developmental skills (motor and language), and the adaptive skills profile (Vineland adaptive behavioral scale) [ Time Frame: at inclusion (Day 1) ]
    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).


Secondary Outcome Measures :
  1. Intellectual functioning assessment (Wechsler scale) [ Time Frame: at inclusion (Day 1) ]
    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.

  2. Raven's Progressive matrices [ Time Frame: at inclusion (Day 1) ]
    The Raven's Progressives matrices test will allow to assess the non-verbal reasoning mental age of the patient

  3. Peabody Picture Vocabulary Test Revised [ Time Frame: at inclusion (Day 1) ]
    The Peabody Picture Vocabulary Test Revised will allow to determine the Vocabulary age (receptive language) of the patient.

  4. Edinburgh handedness test [ Time Frame: at inclusion (Day 1) ]
    The Edinburgh handedness test will assess the handedness of the patients.

  5. Birth parameters: weight, height and head circumference and APGAR score [ Time Frame: at inclusion (Day 1) ]
    The birth parameters include weight, height and head circumference at birth, as well as the initial cardiac and pulmonary adaptation (APGAR score).

  6. Nisonger child behavior rating form [ Time Frame: at inclusion (Day 1) ]
    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.

  7. Caregiver Burden Inventory Modified [ Time Frame: at inclusion (Day 1) ]
    The Caregiver Burden Inventory Modified will allow the assessment of the impact of mental retardation on the primary caregiver within the family.

  8. Analogical visual reasoning task (behavior assessment) [ Time Frame: at inclusion (Day 1) ]
    This paradigm (HCL/CNRS patented), appropriate for mentally retarded patients provides an objective and quantitative assessment of visual analogical reasoning and cognitive inhibition.

  9. Analogical visual reasoning task (eye-tracking assessment) [ Time Frame: at inclusion (Day 1) ]
    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.

  10. Kinematic analysis of a grasping movement [ Time Frame: at inclusion (Day 1) ]
    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).

  11. Structural neuroimaging by MRI [ Time Frame: at inclusion (Day 1) ]
    Structural brain MRI analysis will determine if a specific morphological neuroanatomical pattern can be found for each X-linked mental retardation gene.

  12. Functional neuroimaging by MRI [ Time Frame: at inclusion (Day 1) ]
    Functional brain MRI analysis will determine if patients with X-linked mental retardation have a specific functional neuroanatomical pattern associated to the reasoning task.

  13. School curriculum: age and type of shool [ Time Frame: at inclusion (Day 1) ]
    The school curriculum will include the age at school entrance, and the type of school the child went to.



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Ages Eligible for Study:   2 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02854956


Contacts
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Contact: Vincent DESPORTES, Pr (0)4 27 85 67 61 ext +33 vincent.desportes@chu-lyon.fr
Contact: Sonia GALLETTI (0)4 27 85 77 39 ext +33 sonia.galletti@chu-lyon.fr

Locations
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France
Groupement Hospitalier Est - Hôpital Femme Mère Enfant - Service de neurologie pédiatrique Recruiting
Bron, France, 69500
Contact: Vincent DESPORTES, Pr    (0)4 27 85 67 61 ext +33    vincent.desportes@chu-lyon.fr   
Contact: Sonia GALLETTI    (0)4 27 85 77 39 ext +33    sonia.galletti@chu-lyon.fr   
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
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Principal Investigator: Vincent DESPORTES, Pr Groupement Hospitalier Est - Hôpital Femme Mère Enfant - Service de neurologie pédiatrique

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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT02854956     History of Changes
Other Study ID Numbers: 2010-609
First Posted: August 4, 2016    Key Record Dates
Last Update Posted: July 12, 2017
Last Verified: July 2017

Keywords provided by Hospices Civils de Lyon:
phenotype
X-linked mental retardation
neuronal networks
cognitive processes

Additional relevant MeSH terms:
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Mental Retardation, X-Linked
Genetic Diseases, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Neurodevelopmental Disorders
Mental Disorders
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System