<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/NCT03287206</url>
  </required_header>
  <id_info>
    <org_study_id>THAUVIN PRME 2015</org_study_id>
    <nct_id>NCT03287206</nct_id>
  </id_info>
  <brief_title>Medico-economic Evaluation of Different High-throughput Sequencing Strategies in the Diagnosis of Patients With Intellectual Deficiency</brief_title>
  <acronym>DISSEQ</acronym>
  <official_title>Medico-economic Evaluation of Different High-throughput Sequencing Strategies in the Diagnosis of Patients With Intellectual Deficiency</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire Dijon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Hospitalier Universitaire Dijon</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Intellectual deficiency (ID) is a veritable public health issue because it affects 1 to 3% of&#xD;
      the population at large. Currently, in France, the diagnosis is based on clinical expertise,&#xD;
      the use of DNA microarray analysis, screening for fragile-X syndrome and, if necessary, a&#xD;
      study of target genes depending on the clinical data. Although clinical expertise is not&#xD;
      enough to target one gene in particular, these different tools currently lead to diagnosis in&#xD;
      only 20% of patients on average (higher percentage in cases of syndromic intellectual&#xD;
      deficiency), sometimes after numerous expensive biological examinations.&#xD;
&#xD;
      Thanks to high-throughput sequencing (HTS), medical genetics is experiencing a major&#xD;
      technological upheaval, originating from the development of sequencing panels of target&#xD;
      genes, such as, for example, the DI459 panel, composed of 459 genes implicated in or likely&#xD;
      to be implicated in ID, developed by the team in Strasbourg and whole-exome sequencing (WES).&#xD;
      The deployment of HTS in diagnosis has occurred at different speeds depending on the country,&#xD;
      some of which have been using it in routine diagnosis for several years. The type of strategy&#xD;
      to adopt in development anomalies is still a matter of debate in France, in the absence of&#xD;
      results from cost-effectiveness analyses; this absence has hampered the implementation of&#xD;
      these technologies.&#xD;
&#xD;
      In the diagnosis of ID, the DI459 panel has a diagnostic yield of 25%. Data in the literature&#xD;
      also show a high efficacy of WES in patients with ID: approximately 32% of genetic diagnoses&#xD;
      (progressively increasing thanks to possible reanalysis as knowledge of genomics advances)&#xD;
      and 10% of additional diagnoses through the identification of chromosomal&#xD;
      micro-rearrangements, making an expected total of 42% of diagnoses. WES could thus replace&#xD;
      array-CGH. The cost is higher than that for the DI44 and DI459 panels, but it means that&#xD;
      examinations don't have to be repeated sequentially over time if the investigations are&#xD;
      negative.&#xD;
&#xD;
      The question of medico-economic value is thus central so as to determine which strategy is&#xD;
      the most effective. A few medico-economic studies, comparing classical investigations with&#xD;
      WES, have already been carried out concerning the use of HTS for diagnostic purposes, but&#xD;
      none have concerned ID, or compared panel sequencing with WES. In this context, a&#xD;
      medico-economic study is essential in France, because ultimately the choice of the most&#xD;
      appropriate HTS strategy in the diagnosis of ID will have major repercussions not only&#xD;
      clinical and economic, but also for society at large, on the one hand because of the benefits&#xD;
      1) for the management and prognosis of patients, and 2) for families as they will have&#xD;
      improved access to genetic counselling. It is important to note that the Genetic community&#xD;
      has never experienced such a huge technological innovation, which will lead to a massive&#xD;
      increase in diagnostic yield, thus justifying the interest that the community must give to&#xD;
      this innovation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 28, 2017</start_date>
  <completion_date type="Anticipated">September 2021</completion_date>
  <primary_completion_date type="Actual">December 27, 2018</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Incremental cost-effectiveness ratio of the strategy &quot;screening for fragile-X syndrome + WES&quot; compared with the strategy &quot;ArrayCGH + screening for fragile-X syndrome + DI459 panel&quot;</measure>
    <time_frame>through study completion, an average of 2 years</time_frame>
  </primary_outcome>
  <enrollment type="Anticipated">330</enrollment>
  <condition>Intellectual Deficiency</condition>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>blood samples from children</intervention_name>
    <description>CGH array, Fragile-X syndrome screening, DI459 panel, WES</description>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>blood samples from parents</intervention_name>
    <description>secondary controls for children's analyses</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        patients attending a consultation for intellectual deficiency&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients (children and adults) with intellectual deficiency (ID), whatever the degree&#xD;
&#xD;
          -  Absence of a clear clinical diagnosis at the first consultation for the dysmorphology&#xD;
             assessment&#xD;
&#xD;
          -  Patients who have never undergone genetic investigations&#xD;
&#xD;
          -  Consent of the patient or his/her legal representative&#xD;
&#xD;
          -  Patient with national health insurance cover&#xD;
&#xD;
          -  Samples available from both parents&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breast-feeding women&#xD;
&#xD;
          -  Patients presenting learning disorders&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Chu Dijon Bourogne</name>
      <address>
        <city>Dijon</city>
        <zip>21000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chirstel THAUVIN-ROBINET</last_name>
      <phone>03.80.29.53.13</phone>
      <email>christel.thauvin@chu-dijon.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>August 22, 2017</study_first_submitted>
  <study_first_submitted_qc>September 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <last_update_submitted>August 3, 2021</last_update_submitted>
  <last_update_submitted_qc>August 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT03287206
org study id: THAUVIN PRME 2015
nct id: NCT03287206
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Intellectual deficiency (ID) is a veritable public health issue because it affects 1 to 3% of
      the population at large. Currently, in France, the diagnosis is based on clinical expertise,
      the use of DNA microarray analysis, screening for fragile-X syndrome and, if necessary, a
      study of target genes depending on the clinical data. Although clinical expertise is not
      enough to target one gene in particular, these different tools currently lead to diagnosis in
      only 20% of patients on average (higher percentage in cases of syndromic intellectual
      deficiency), sometimes after numerous expensive biological examinations.

      Thanks to high-throughput sequencing (HTS), medical genetics is experiencing a major
      technological upheaval, originating from the development of sequencing panels of target
      genes, such as, for example, the DI459 panel, composed of 459 genes implicated in or likely
      to be implicated in ID, developed by the team in Strasbourg and whole-exome sequencing (WES).
      The deployment of HTS in diagnosis has occurred at different speeds depending on the country,
      some of which have been using it in routine diagnosis for several years. The type of strategy
      to adopt in development anomalies is still a matter of debate in France, in the absence of
      results from cost-effectiveness analyses; this absence has hampered the implementation of
      these technologies.

      In the diagnosis of ID, the DI459 panel has a diagnostic yield of 25%. Data in the literature
      also show a high efficacy of WES in patients with ID: approximately 32% of genetic diagnoses
      (progressively increasing thanks to possible reanalysis as knowledge of genomics advances)
      and 10% of additional diagnoses through the identification of chromosomal
      micro-rearrangements, making an expected total of 42% of diagnoses. WES could thus replace
      array-CGH. The cost is higher than that for the DI44 and DI459 panels, but it means that
      examinations don't have to be repeated sequentially over time if the investigations are
      negative.

      The question of medico-economic value is thus central so as to determine which strategy is
      the most effective. A few medico-economic studies, comparing classical investigations with
      WES, have already been carried out concerning the use of HTS for diagnostic purposes, but
      none have concerned ID, or compared panel sequencing with WES. In this context, a
      medico-economic study is essential in France, because ultimately the choice of the most
      appropriate HTS strategy in the diagnosis of ID will have major repercussions not only
      clinical and economic, but also for society at large, on the one hand because of the benefits
      1) for the management and prognosis of patients, and 2) for families as they will have
      improved access to genetic counselling. It is important to note that the Genetic community
      has never experienced such a huge technological innovation, which will lead to a massive
      increase in diagnostic yield, thus justifying the interest that the community must give to
      this innovation.
observational model: Cohort
time perspective: Prospective
measure: Incremental cost-effectiveness ratio of the strategy "screening for fragile-X syndrome + WES" compared with the strategy "ArrayCGH + screening for fragile-X syndrome + DI459 panel"
time frame: through study completion, an average of 2 years
intervention type: Biological
intervention name: blood samples from children
description: CGH array, Fragile-X syndrome screening, DI459 panel, WES
intervention type: Biological
intervention name: blood samples from parents
description: secondary controls for children's analyses
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor