<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04436588</url>
  </required_header>
  <id_info>
    <org_study_id>RECHMPL20_0353</org_study_id>
    <nct_id>NCT04436588</nct_id>
  </id_info>
  <brief_title>Better Delineation of DDX3X Related Phenotype and Epigenetic Signature.</brief_title>
  <official_title>DDX3X Related Disorder : Clinical Phenotype, Neuropsychological Profile and Epigenetic Signature.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Montpellier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Association Xtraordinaire sub-group DDX3X</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Genida</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Montpellier</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      DDX3X related disorder is mainly characterised by developmental delay (DD) and intellectual&#xD;
      disability (ID), ranging from mild to severe, and neuroimaging abnormalities.&#xD;
&#xD;
      The aims of this study are first to better delineate the clinical phenotype, as well as the&#xD;
      neuropsychological profile and, second, to study the epigenetic signature in a cohort of&#xD;
      individuals with DDX3X pathogenic variants. This work will conduct to a MD thesis of a&#xD;
      clinical resident geneticist in France.&#xD;
&#xD;
      Physician that will participate will fill an Excel sheet regarding the clinical and&#xD;
      neuropsychological assessment. The investigators will be also happy to have a DNA sample with&#xD;
      a minimum 0.5ug of peripheral blood genomic DNA. The investigators will gather the DNA in&#xD;
      Montpellier genetic lab (Dr Mouna BARAT) and send the batch to the Dr Sadikovic' lab.&#xD;
&#xD;
      Between 2018 and 2020, the investigators have already recruited data from individuals with&#xD;
      DDX3X pathogenic variants from several European and Asian genetic centres&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators aim to better understand and delineate the genetic syndrome DDX3X.&#xD;
&#xD;
      This genetic disorder was described in 2015 by Lot Snijders Blok et al. (DOI&#xD;
      https://doi.org/10.1016/j.ajhg.2015.07.004:).&#xD;
&#xD;
      Since this first publication of 38 female individuals carrying a pathogenic mutation DDX3X,&#xD;
      15 more individuals have been reported.&#xD;
&#xD;
      The investigators are seeking to better define the phenotype of individuals with pathogenic&#xD;
      variants of DDX3X, to better understand intellectual functioning as well as the strengths and&#xD;
      weaknesses of intellectual functioning by collecting standardized neuropsychological&#xD;
      assessments already performed such as WPPSI/WISC and WAIS. For this purpose, the&#xD;
      investigators will gather clinical and neuropsychological data already carried out in the&#xD;
      context of care.&#xD;
&#xD;
      Finally, the investigators will attempt to identify an epigenetic signature in this genetic&#xD;
      disease. To this end, the investigators will collect genomic DNA from peripheral blood&#xD;
      already collected for genetic analysis and send an anonymized batch of samples to our&#xD;
      collaborator, Dr. Bekim Sadicovik. Dr. Bekim Sadicovik and his team will compare the&#xD;
      epigenetic DNA methylation-type markers with the corresponding sex and age controls. If&#xD;
      specific probes are abnormally methylated in DDX3X individuals, this will determine a&#xD;
      disease-specific epigenetic signature. The investigators will then be able to propose an&#xD;
      epigenetic signature for individuals with uncharacterized DDX3X variations (class 3, VUS).&#xD;
      This method will make it possible to define whether the variation is responsible for the&#xD;
      disease or not without going through functional analysis steps that are difficult to&#xD;
      implement routinely.&#xD;
&#xD;
      The expected benefits are a better understanding of DDX3X disease, keys to neuropsychological&#xD;
      rehabilitation, a better understanding of human brain functions, the possibility of proposing&#xD;
      an epigenetic signature for people in whom it is not possible to decide whether a variation&#xD;
      in the DDX3X gene is pathological or not&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date type="Actual">November 1, 2019</start_date>
  <completion_date type="Anticipated">December 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Neuropsychological phenotype will be assessed using Wechsler scales</measure>
    <time_frame>1 day</time_frame>
    <description>DDX3X related clinical and neuropsychological phenotype. Neuropsychological phenotype will be assessed using Wechsler scales. The phenotype of individuals will be assessed using a questionnaire sent to their geneticist</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measurement and comparison of the methylation of the cpg sites&quot;</measure>
    <time_frame>1 day</time_frame>
    <description>Epigenetic signature will be investigated by measurement and comparison of the methylation of the cpg sites</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Intellectual Developmental Disorder</condition>
  <condition>X-LINKED</condition>
  <arm_group>
    <arm_group_label>DDX3X</arm_group_label>
    <description>DDX3X</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Epigenetic signatures</intervention_name>
    <description>Epigenetic signatures (Dr Sadikovic' lab, London, Ontario, Canada)</description>
    <arm_group_label>DDX3X</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Individuals with DDX3X pathogenic Variant&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
        - DDX3X pathogenic Variant&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  no pathogenic variant in DDX3X&#xD;
&#xD;
          -  no consent for the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David GENEVIEVE</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Medical Genetics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UH Montpellier</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>June 16, 2020</last_update_submitted>
  <last_update_submitted_qc>June 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>DDX3X</keyword>
  <keyword>Syndromic</keyword>
  <keyword>SNIJDERS BLOK</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intellectual Disability</mesh_term>
    <mesh_term>Developmental Disabilities</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>NC</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04436588
org study id: RECHMPL20_0353
nct id: NCT04436588
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
DDX3X related disorder is mainly characterised by developmental delay (DD) and intellectual
      disability (ID), ranging from mild to severe, and neuroimaging abnormalities.

      The aims of this study are first to better delineate the clinical phenotype, as well as the
      neuropsychological profile and, second, to study the epigenetic signature in a cohort of
      individuals with DDX3X pathogenic variants. This work will conduct to a MD thesis of a
      clinical resident geneticist in France.

      Physician that will participate will fill an Excel sheet regarding the clinical and
      neuropsychological assessment. The investigators will be also happy to have a DNA sample with
      a minimum 0.5ug of peripheral blood genomic DNA. The investigators will gather the DNA in
      Montpellier genetic lab (Dr Mouna BARAT) and send the batch to the Dr Sadikovic' lab.

      Between 2018 and 2020, the investigators have already recruited data from individuals with
      DDX3X pathogenic variants from several European and Asian genetic centres
The investigators aim to better understand and delineate the genetic syndrome DDX3X.

      This genetic disorder was described in 2015 by Lot Snijders Blok et al. (DOI
      https://doi.org/10.1016/j.ajhg.2015.07.004:).

      Since this first publication of 38 female individuals carrying a pathogenic mutation DDX3X,
      15 more individuals have been reported.

      The investigators are seeking to better define the phenotype of individuals with pathogenic
      variants of DDX3X, to better understand intellectual functioning as well as the strengths and
      weaknesses of intellectual functioning by collecting standardized neuropsychological
      assessments already performed such as WPPSI/WISC and WAIS. For this purpose, the
      investigators will gather clinical and neuropsychological data already carried out in the
      context of care.

      Finally, the investigators will attempt to identify an epigenetic signature in this genetic
      disease. To this end, the investigators will collect genomic DNA from peripheral blood
      already collected for genetic analysis and send an anonymized batch of samples to our
      collaborator, Dr. Bekim Sadicovik. Dr. Bekim Sadicovik and his team will compare the
      epigenetic DNA methylation-type markers with the corresponding sex and age controls. If
      specific probes are abnormally methylated in DDX3X individuals, this will determine a
      disease-specific epigenetic signature. The investigators will then be able to propose an
      epigenetic signature for individuals with uncharacterized DDX3X variations (class 3, VUS).
      This method will make it possible to define whether the variation is responsible for the
      disease or not without going through functional analysis steps that are difficult to
      implement routinely.

      The expected benefits are a better understanding of DDX3X disease, keys to neuropsychological
      rehabilitation, a better understanding of human brain functions, the possibility of proposing
      an epigenetic signature for people in whom it is not possible to decide whether a variation
      in the DDX3X gene is pathological or not
observational model: Cohort
time perspective: Other
measure: Neuropsychological phenotype will be assessed using Wechsler scales
time frame: 1 day
description: DDX3X related clinical and neuropsychological phenotype. Neuropsychological phenotype will be assessed using Wechsler scales. The phenotype of individuals will be assessed using a questionnaire sent to their geneticist
measure: Measurement and comparison of the methylation of the cpg sites"
time frame: 1 day
description: Epigenetic signature will be investigated by measurement and comparison of the methylation of the cpg sites
arm group label: DDX3X
description: DDX3X
intervention type: Genetic
intervention name: Epigenetic signatures
description: Epigenetic signatures (Dr Sadikovic' lab, London, Ontario, Canada)
arm group label: DDX3X
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: David GENEVIEVE
role: Principal Investigator
affiliation: Department of Medical Genetics
facility: 
country: France
responsible party type: Sponsor
mesh term: Intellectual Disability
mesh term: Developmental Disabilities
sharing ipd: Undecided
ipd description: NC