<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/NCT04406480</url>
  </required_header>
  <id_info>
    <org_study_id>7344</org_study_id>
    <nct_id>NCT04406480</nct_id>
  </id_info>
  <brief_title>Realization of Sequencing of All Known Human Genes in Case of Detection of Cerebral, Renal or Ophthalmological Fetal Malformations During Pregnancy in Order to Make an Etiological Diagnosis and to Precise the Fetal Prognosis</brief_title>
  <acronym>PRENATEX</acronym>
  <official_title>Contribution of the Exome Sequencing in Antenatal Period Behind Ultrasound Features Suggestive of a Rare Genetic Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Strasbourg, France</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Strasbourg, France</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>
      Congenital malformations concern 3% of pregnancies; most of them can be seen during&#xD;
      pregnancy. For some malformations, an invasive sample (trophoblast biopsy or amniocentesis)&#xD;
      is proposed to search a chromosomal abnormality by the technique of DNA chip. However, some&#xD;
      strongly suggestive signs of a genetic (and not chromosomal) pathology have a very low&#xD;
      diagnostic rate with this technique. In the absence of an etiological diagnosis, the&#xD;
      prognosis for the unborn child is very difficult to assess, as we can't know if the fetal&#xD;
      malformation is really isolated or associted to other unseen features as part of a syndromic&#xD;
      condition.&#xD;
&#xD;
      For some malformations strongly suggestive of a genetic condition, we propose to realize an&#xD;
      exome (i.e. all coding parts of the genome) sequencing of the trio (child and the 2 parents)&#xD;
      with a delivery time compatible with the emergency situation of a pregnancy (6 weeks&#xD;
      maximum). We will apply bioinformatics filters to analyse only genes known to be involved in&#xD;
      the malformation present in the unborn child and thus avoid the identification of variants in&#xD;
      unrelated genes. These lists of genes have been previously validated by the Rare Disease&#xD;
      Health Sectors and the affiliated diagnostic laboratories. The selected malformations are: 1)&#xD;
      anomalies of the central nervous system (microcephaly (&lt;- 2DS) with anomalies of gyration,&#xD;
      anomalies of the posterior fossa, anomalies of the midline except agenesis of the corpus&#xD;
      callosum), 2) ophthalmological anomalies (microphthalmia, hyperplasia vitreous) and 3) renal&#xD;
      abnormalities (large hyperechoic kidneys).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 5, 2020</start_date>
  <completion_date type="Anticipated">September 2023</completion_date>
  <primary_completion_date type="Anticipated">September 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Diagnostic contribution of the exome sequencing in antenatal period in comparison with the chromosomal analysis (CGH-array) realized in current health care</measure>
    <time_frame>13 months</time_frame>
    <description>Comparison of the number of genetic diagnoses made by exome sequencing and by CGH-array.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effects on pregnancy management and/or postnatal child care due to an etiological diagnosis</measure>
    <time_frame>13 months</time_frame>
    <description>Percentage of antenatal and/or postnatal fetus/child care modified by the molecular result</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Feasibility study of carrying out exome sequencing in the antenatal period in terms of time to deliver results</measure>
    <time_frame>13 months</time_frame>
    <description>Time to results from the inclusion of the trio (in days) specifying the time for each step (reception, sequencing, bioinformatics analysis, interpretation) (in days)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Difficulties of interpretation of the exome sequencing in antenatal period</measure>
    <time_frame>13 months</time_frame>
    <description>Numbers of variants of unknown signification identified by exome sequencing with and without bioinformatic filters (targeted exome)</description>
  </other_outcome>
  <other_outcome>
    <measure>Identification of new genes responsible of fetal malformations</measure>
    <time_frame>13 months</time_frame>
    <description>If the results of CGH-array and targeted exome sequencing are negative, analysis of the entire exome sequencing to find new genes implicated in fetal development</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Fetal Malformation</condition>
  <condition>Pregnancy Related</condition>
  <condition>Rare Genetic Disease</condition>
  <arm_group>
    <arm_group_label>90 trios (270 subjects: 90 fetus, 90 mothers, 90 fathers)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>CGH-array and exome sequencing</intervention_name>
    <description>A blood sample will be used for CGH-array and exome sequencing</description>
    <arm_group_label>90 trios (270 subjects: 90 fetus, 90 mothers, 90 fathers)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Father and mother of an unborn child past the age of majority&#xD;
&#xD;
          -  Consent dated and signed by the mother and by the father&#xD;
&#xD;
          -  Father and mother able to understand the objectives and risks of the study&#xD;
&#xD;
          -  For the mother, pregnancy in progress (between 12 and 34 weeks)&#xD;
&#xD;
          -  For the mother, pregnancy with the presence of a malformation on ultrasound, confirmed&#xD;
             by a doctor from the multidisciplinary diagnostic prenatal center, entering into the&#xD;
             indications retained for this study&#xD;
&#xD;
          -  Clinical validation of the couple's eligibility by an expert for some of selected&#xD;
             indications&#xD;
&#xD;
          -  Father and mother affiliated to a social protection health&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Identified genetic or chromosomal abnormality explaining the observed malformation&#xD;
&#xD;
          -  Inability to give informations to the father and / or mother (father or mother in&#xD;
             emergency or life-threatening situation)&#xD;
&#xD;
          -  Father and / or mother under the protection of justice&#xD;
&#xD;
          -  Father and / or mother under guardianship or curatorship&#xD;
&#xD;
          -  Nursing woman&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Elise SCHAEFER</last_name>
    <phone>+33 3 88 12 81 20</phone>
    <email>elise.schaefer@chru-strasbourg.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>CHu de Besançon</name>
      <address>
        <city>Besançon</city>
        <zip>25030</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Lionel VAN MALDERGEM</last_name>
      <phone>+33 3 81 21 81 87</phone>
      <email>lionel.van-maldergem@inserm.fr</email>
    </contact>
    <investigator>
      <last_name>Lionel VAN MALDERGEM</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Juliette PIARD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Elise BOUCHER</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Dijon</name>
      <address>
        <city>Dijon</city>
        <zip>21079</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Christel THAUVIN</last_name>
      <phone>+33 3 80 29 53 13</phone>
      <email>Christel.thauvin@chu-dijon.fr</email>
    </contact>
    <investigator>
      <last_name>Christel THAUVIN</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Laurence FAIVRE</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Arthur SORLIN</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sébastien MOUTTON</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospices Civils de Lyon</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Audrey PUTOUX</last_name>
      <phone>+33 4 27 85 50 83</phone>
      <email>Audrey.putoux@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Audrey PUTOUX</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Groupe Hospitalier Region Mulhouse Et Sud Alsace</name>
      <address>
        <city>Mulhouse</city>
        <zip>68070</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Emmanuelle GINGLINGER</last_name>
      <phone>+33 3 89 64 87 03</phone>
      <email>GINGLINGERE@ghrmsa.fr</email>
    </contact>
    <investigator>
      <last_name>Emmanuelle GINGLINGER</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Edgar MONTOYA RAMIREZ</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Nancy</name>
      <address>
        <city>Nancy</city>
        <zip>54042</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Laetitia LAMBERT</last_name>
      <phone>+33 3 83 34 43 76</phone>
      <email>l.lambert@chru-nancy.fr</email>
    </contact>
    <investigator>
      <last_name>Laetitia LAMBERT</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Bruno LEHEUP</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital d'Enfants Armand-Trousseau</name>
      <address>
        <city>Paris</city>
        <zip>75012</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Alexandra AFENJAR</last_name>
      <phone>+33 1 44 73 61 86</phone>
      <email>Alexandra.afenjar@aphp.fr</email>
    </contact>
    <investigator>
      <last_name>Alexandra AFENJAR</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital de la Pitié Salpêtrière</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Delphine HERON</last_name>
      <phone>+33 1 42 16 13 47</phone>
      <email>Delphine.heron@aphp.fr</email>
    </contact>
    <investigator>
      <last_name>Delphine HERON</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Necker Enfants Malades</name>
      <address>
        <city>Paris</city>
        <zip>75743</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Tania ATTIE-BITACH</last_name>
      <phone>+33 1 44 49 51 44</phone>
      <email>tania.attie@inserm.fr</email>
    </contact>
    <investigator>
      <last_name>Tania ATTIE-BITACH</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Reims</name>
      <address>
        <city>Reims</city>
        <zip>51092</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Martine DOCO-FENZY</last_name>
      <phone>+33 3 26 78 90 03</phone>
      <email>mdocofenzy@chu-reims.fr</email>
    </contact>
    <investigator>
      <last_name>Martine DOCO-FENZY</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Céline POIRSIER</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Rennes</name>
      <address>
        <city>Rennes</city>
        <zip>35203</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Sylvie ODENT</last_name>
      <phone>+33 2 99 26 67 44</phone>
      <email>Sylvie.odent@chu-rennes.fr</email>
    </contact>
    <investigator>
      <last_name>Sylvie ODENT</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Les Hôpitaux Universitaires de Strasbourg</name>
      <address>
        <city>Strasbourg</city>
        <zip>67098</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elise SCHAEFER</last_name>
      <phone>+33 3 88 12 81 20</phone>
      <email>elise.schaefer@chru-strasbourg.fr</email>
    </contact>
    <investigator>
      <last_name>Elise SCHAEFER</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Hélène DOLLFUS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Salima EL CHEHADEH</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Romain FAVRE</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Vincent LAUGEL</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Toulouse</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Patrick CALVAS</last_name>
      <phone>+33 5 61 77 90 51</phone>
      <email>calvas.p@chu-toulouse.fr</email>
    </contact>
    <investigator>
      <last_name>Patrick CALVAS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>November 10, 2020</last_update_submitted>
  <last_update_submitted_qc>November 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Fetal malformations</keyword>
  <keyword>Exome sequencing</keyword>
  <keyword>antenatal cerebral malformations</keyword>
  <keyword>antenatal ocular malformations</keyword>
  <keyword>antenatal large hyperechoic kidneys</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Congenital Abnormalities</mesh_term>
    <mesh_term>Genetic Diseases, Inborn</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT04406480
org study id: 7344
nct id: NCT04406480
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Congenital malformations concern 3% of pregnancies; most of them can be seen during
      pregnancy. For some malformations, an invasive sample (trophoblast biopsy or amniocentesis)
      is proposed to search a chromosomal abnormality by the technique of DNA chip. However, some
      strongly suggestive signs of a genetic (and not chromosomal) pathology have a very low
      diagnostic rate with this technique. In the absence of an etiological diagnosis, the
      prognosis for the unborn child is very difficult to assess, as we can't know if the fetal
      malformation is really isolated or associted to other unseen features as part of a syndromic
      condition.

      For some malformations strongly suggestive of a genetic condition, we propose to realize an
      exome (i.e. all coding parts of the genome) sequencing of the trio (child and the 2 parents)
      with a delivery time compatible with the emergency situation of a pregnancy (6 weeks
      maximum). We will apply bioinformatics filters to analyse only genes known to be involved in
      the malformation present in the unborn child and thus avoid the identification of variants in
      unrelated genes. These lists of genes have been previously validated by the Rare Disease
      Health Sectors and the affiliated diagnostic laboratories. The selected malformations are: 1)
      anomalies of the central nervous system (microcephaly (<- 2DS) with anomalies of gyration,
      anomalies of the posterior fossa, anomalies of the midline except agenesis of the corpus
      callosum), 2) ophthalmological anomalies (microphthalmia, hyperplasia vitreous) and 3) renal
      abnormalities (large hyperechoic kidneys).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Diagnostic contribution of the exome sequencing in antenatal period in comparison with the chromosomal analysis (CGH-array) realized in current health care
time frame: 13 months
description: Comparison of the number of genetic diagnoses made by exome sequencing and by CGH-array.
measure: Effects on pregnancy management and/or postnatal child care due to an etiological diagnosis
time frame: 13 months
description: Percentage of antenatal and/or postnatal fetus/child care modified by the molecular result
measure: Feasibility study of carrying out exome sequencing in the antenatal period in terms of time to deliver results
time frame: 13 months
description: Time to results from the inclusion of the trio (in days) specifying the time for each step (reception, sequencing, bioinformatics analysis, interpretation) (in days)
measure: Difficulties of interpretation of the exome sequencing in antenatal period
time frame: 13 months
description: Numbers of variants of unknown signification identified by exome sequencing with and without bioinformatic filters (targeted exome)
measure: Identification of new genes responsible of fetal malformations
time frame: 13 months
description: If the results of CGH-array and targeted exome sequencing are negative, analysis of the entire exome sequencing to find new genes implicated in fetal development
arm group label: 90 trios (270 subjects: 90 fetus, 90 mothers, 90 fathers)
arm group type: Other
intervention type: Genetic
intervention name: CGH-array and exome sequencing
description: A blood sample will be used for CGH-array and exome sequencing
arm group label: 90 trios (270 subjects: 90 fetus, 90 mothers, 90 fathers)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Elise SCHAEFER
phone: +33 3 88 12 81 20
email: elise.schaefer@chru-strasbourg.fr
facility: 
status: Not yet recruiting
contact: 
investigator: 
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status: Not yet recruiting
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status: Not yet recruiting
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status: Not yet recruiting
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status: Not yet recruiting
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status: Not yet recruiting
contact: 
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status: Recruiting
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status: Not yet recruiting
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country: France
responsible party type: Sponsor
mesh term: Congenital Abnormalities
mesh term: Genetic Diseases, Inborn
sharing ipd: Undecided