<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/NCT03831035</url>
  </required_header>
  <id_info>
    <org_study_id>RECHMPL17_0387</org_study_id>
    <nct_id>NCT03831035</nct_id>
  </id_info>
  <brief_title>Fast Exome for Diagnosis of Congenital Conditions in Infants Under 12 Months of Age Hospitalized in Intensive Care Unit</brief_title>
  <acronym>REUNIR</acronym>
  <official_title>Fast Exome for Diagnosis of Congenital Conditions in Infants Under 12 Months of Age Hospitalized in Intensive Care Unit</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Montpellier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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>
      An early diagnosis of congenital malformations and suspected genetic conditions in critically&#xD;
      ill infants is essential to perform specific adapted care, prevention, and give proper&#xD;
      genetic counseling. However, etiologies are various and each of them is individually very&#xD;
      rare. Thanks to next-generation sequencing technologies, diagnosis time frames have&#xD;
      drastically decreased and the investigators have observed an increase in diagnosis yields.&#xD;
&#xD;
      This study aims to evaluate the feasibility of fast trio exome sequencing (less than 16 days&#xD;
      between informed consent signature and the consultation for results to the parents) in&#xD;
      infants under the age of 12 months hospitalized in Intensive Care Unit (ICU).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This prospective study is the first French study aiming to evaluate the feasibility of fast&#xD;
      trio exome sequencing (less than 16 days between informed consent signature and consultation&#xD;
      for results presentation to the parents) in 15 infants under the age of 12 months&#xD;
      hospitalized in the Intensive Care Unit. Included patients will have a year of follow-up&#xD;
      examination.&#xD;
&#xD;
      The main evaluation criterion is the yield of exome results given to the family before 16&#xD;
      days. The secondary evaluation criteria are 1/ duration of each step until the results 2/&#xD;
      diagnosis yield : identification of the etiology 3/ adjustment of medical care allowed by the&#xD;
      exome diagnosis 4/quantity of blood necessary to achieve diagnosis 5/ duration of hospital&#xD;
      stay and number of medical consultations in the year following inclusion.&#xD;
&#xD;
      Exome sequencing will be performed on top of classical analysis ordinarily prescribed.&#xD;
      Medical care will not be modified until exome results reception. After signature of informed&#xD;
      consent, blood samples of the infant and both parents will be used for trio exome sequencing,&#xD;
      which includes 3 steps : the analytical step (blood sample DNA extraction and high-throughput&#xD;
      sequencing), the bioinformatic step, and the interpretation step.&#xD;
&#xD;
      The study includes four medical consultations:&#xD;
&#xD;
      1/consultation with a geneticist for inclusion, 2/consultation with a geneticist to give the&#xD;
      exome results, 3/ consultation at 3 months after the results for the sanger-confirmation of&#xD;
      the exome result, 4/ consultation at one year after the inclusion for medical follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 8, 2019</start_date>
  <completion_date type="Anticipated">March 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2021</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>Yield of exome results given to the family before 16 days</measure>
    <time_frame>16 days maximum after inclusion</time_frame>
    <description>number of days between the collect sample and results</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of each step until the results (the analytical step, the bioinformatic step, the interpretation step).</measure>
    <time_frame>16 days maximum after inclusion</time_frame>
    <description>number of days between the collect sample and results</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diagnosis yield : identification of the etiology</measure>
    <time_frame>3 months</time_frame>
    <description>number of days between the collect sample and diagnostic confirmation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adjustment of medical care allowed by the exome diagnosis</measure>
    <time_frame>16 days maximum after inclusion</time_frame>
    <description>Any additions or deletions of a diagnostic exam, medical care specific to the diagnosed pathology or screening of a known complication</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantity of blood necessary to achieve diagnosis</measure>
    <time_frame>16 days maximum after inclusion</time_frame>
    <description>blood volume necessary to achieve diagnosis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantity of blood necessary to achieve diagnosis</measure>
    <time_frame>16 days maximum after inclusion</time_frame>
    <description>number of samples necessary to achieve diagnosis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>duration of hospital stay in the year following inclusion</measure>
    <time_frame>a year after inclusion</time_frame>
    <description>number of days of hospital stay in the year</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>number of medical consultations in the year following inclusion</measure>
    <time_frame>a year after inclusion</time_frame>
    <description>number of medical consultations in the year</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Infant, Newborn, Diseases</condition>
  <condition>Congenital Malformations</condition>
  <condition>Intensive Care Unit</condition>
  <condition>Neurologic Symptoms</condition>
  <arm_group>
    <arm_group_label>15 patients and both parents.</arm_group_label>
    <description>The patients are aged 12 months or under hospitalized in the ICU suffering from multiple congenital malformations and/or neurologic symptoms.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Genetic analyse by whole exome sequencing</intervention_name>
    <description>Exome sequencing requires analytic, bio informatic and interpretation steps.</description>
    <arm_group_label>15 patients and both parents.</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      It is a trio exome sequencing which includes 3 steps : the analytical step (blood sample DNA&#xD;
      extraction and high-throughput sequencing), the bioinformatic step, and the interpretation&#xD;
      step.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        This study includes 15 patients and both parents. The patients are aged 12 months or under&#xD;
        hospitalized in the ICU suffering from multiple congenital malformations and/or neurologic&#xD;
        symptoms&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Infant aged under 12 months , hospitalized in the ICU.&#xD;
&#xD;
          -  Infant with multiple congenital malformations or neurological symptoms for which a&#xD;
             genetic origin is suspected but undiagnosed genetically.&#xD;
&#xD;
          -  Infant for whom both biological parents have given consent for the study, genetic&#xD;
             analysis for themselves anf their child.&#xD;
&#xD;
          -  Infant and parents registered in the French National health service&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Absence of one or both parental sample.&#xD;
&#xD;
          -  Precise genetic diagnosis made pre- or post-natally with chromosomal (I.e : Down&#xD;
             syndrome), Sanger (i.e : infantile spinal amyotrophia) methylation (i.e : Prader-Willi&#xD;
             syndrome) or triplet amplification (I.e : neonatal Steinert myotonia) studies.&#xD;
&#xD;
          -  Strong clinical evidence for a with chromosomal (I.e : Down syndrome), Sanger (i.e :&#xD;
             infantile spinal amyotrophia) methylation (i.e : Prader-Willi syndrome) or triplet&#xD;
             amplification (I.e : neonatal Steinert myotonia) studies.&#xD;
&#xD;
          -  Impossibility for one or both parents to give his or her consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>12 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marjolaine WILLEMS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical genetics Arnaud de Villeneuve</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marjolaine WILLEMS, MD</last_name>
    <phone>+33467336564</phone>
    <email>m-willems@chu-montpellier.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Mouna BARAT, PharmD, PhD</last_name>
    <phone>0467336152</phone>
    <email>mouna.barat@inserm.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Medical genetics Arnaud de Villeneuve</name>
      <address>
        <city>Montpellier</city>
        <state>Hérault</state>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marjolaine WILLEMS, MD</last_name>
      <phone>+33467336564</phone>
      <email>m-willems@chu-montpellier.fr</email>
    </contact>
    <contact_backup>
      <last_name>Mouna BARAT, PhD</last_name>
      <phone>0467336152</phone>
      <email>mouna.barat@inserm.fr</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
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  <verification_date>April 2020</verification_date>
  <study_first_submitted>January 18, 2019</study_first_submitted>
  <study_first_submitted_qc>February 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 5, 2019</study_first_posted>
  <last_update_submitted>April 20, 2020</last_update_submitted>
  <last_update_submitted_qc>April 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Fast trio exome</keyword>
  <keyword>Multiple congenital malformation</keyword>
  <keyword>Intensive care unit</keyword>
  <keyword>Neurological distress</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neurologic Manifestations</mesh_term>
    <mesh_term>Congenital Abnormalities</mesh_term>
    <mesh_term>Infant, Newborn, Diseases</mesh_term>
  </condition_browse>
  <!-- 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/NCT03831035
org study id: RECHMPL17_0387
nct id: NCT03831035
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
An early diagnosis of congenital malformations and suspected genetic conditions in critically
      ill infants is essential to perform specific adapted care, prevention, and give proper
      genetic counseling. However, etiologies are various and each of them is individually very
      rare. Thanks to next-generation sequencing technologies, diagnosis time frames have
      drastically decreased and the investigators have observed an increase in diagnosis yields.

      This study aims to evaluate the feasibility of fast trio exome sequencing (less than 16 days
      between informed consent signature and the consultation for results to the parents) in
      infants under the age of 12 months hospitalized in Intensive Care Unit (ICU).
This prospective study is the first French study aiming to evaluate the feasibility of fast
      trio exome sequencing (less than 16 days between informed consent signature and consultation
      for results presentation to the parents) in 15 infants under the age of 12 months
      hospitalized in the Intensive Care Unit. Included patients will have a year of follow-up
      examination.

      The main evaluation criterion is the yield of exome results given to the family before 16
      days. The secondary evaluation criteria are 1/ duration of each step until the results 2/
      diagnosis yield : identification of the etiology 3/ adjustment of medical care allowed by the
      exome diagnosis 4/quantity of blood necessary to achieve diagnosis 5/ duration of hospital
      stay and number of medical consultations in the year following inclusion.

      Exome sequencing will be performed on top of classical analysis ordinarily prescribed.
      Medical care will not be modified until exome results reception. After signature of informed
      consent, blood samples of the infant and both parents will be used for trio exome sequencing,
      which includes 3 steps : the analytical step (blood sample DNA extraction and high-throughput
      sequencing), the bioinformatic step, and the interpretation step.

      The study includes four medical consultations:

      1/consultation with a geneticist for inclusion, 2/consultation with a geneticist to give the
      exome results, 3/ consultation at 3 months after the results for the sanger-confirmation of
      the exome result, 4/ consultation at one year after the inclusion for medical follow-up.
observational model: Cohort
time perspective: Prospective
measure: Yield of exome results given to the family before 16 days
time frame: 16 days maximum after inclusion
description: number of days between the collect sample and results
measure: Duration of each step until the results (the analytical step, the bioinformatic step, the interpretation step).
time frame: 16 days maximum after inclusion
description: number of days between the collect sample and results
measure: Diagnosis yield : identification of the etiology
time frame: 3 months
description: number of days between the collect sample and diagnostic confirmation
measure: Adjustment of medical care allowed by the exome diagnosis
time frame: 16 days maximum after inclusion
description: Any additions or deletions of a diagnostic exam, medical care specific to the diagnosed pathology or screening of a known complication
measure: Quantity of blood necessary to achieve diagnosis
time frame: 16 days maximum after inclusion
description: blood volume necessary to achieve diagnosis
measure: Quantity of blood necessary to achieve diagnosis
time frame: 16 days maximum after inclusion
description: number of samples necessary to achieve diagnosis
measure: duration of hospital stay in the year following inclusion
time frame: a year after inclusion
description: number of days of hospital stay in the year
measure: number of medical consultations in the year following inclusion
time frame: a year after inclusion
description: number of medical consultations in the year
arm group label: 15 patients and both parents.
description: The patients are aged 12 months or under hospitalized in the ICU suffering from multiple congenital malformations and/or neurologic symptoms.
intervention type: Other
intervention name: Genetic analyse by whole exome sequencing
description: Exome sequencing requires analytic, bio informatic and interpretation steps.
arm group label: 15 patients and both parents.
It is a trio exome sequencing which includes 3 steps : the analytical step (blood sample DNA
      extraction and high-throughput sequencing), the bioinformatic step, and the interpretation
      step.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Day
maximum age: 12 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Marjolaine WILLEMS
role: Principal Investigator
affiliation: Medical genetics Arnaud de Villeneuve
last name: Marjolaine WILLEMS, MD
phone: +33467336564
email: m-willems@chu-montpellier.fr
last name: Mouna BARAT, PharmD, PhD
phone: 0467336152
email: mouna.barat@inserm.fr
facility: 
status: Recruiting
contact: 
contact backup: 
country: France
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responsible party type: Sponsor
mesh term: Neurologic Manifestations
mesh term: Congenital Abnormalities
mesh term: Infant, Newborn, Diseases