xml: <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/NCT05976841</url>
    </required_header>
    <id_info>
      <org_study_id>C15-65</org_study_id>
      <nct_id>NCT05976841</nct_id>
    </id_info>
    <brief_title>SEDVasc (RaDiCo Cohort) (RaDiCo-SEDVasc)</brief_title>
    <official_title>National Cohort on the Vascular Ehlers-Danlos Syndrome (SEDv)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Institut National de la Santé Et de la Recherche Médicale, 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>
        The goal of this observational study is to describe the natural course of vascular&#xD;
        Ehlers-Danlos syndrome, in particular the order of appearance of different types of&#xD;
        complications (arterial, digestive, pulmonary and uterine).&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">December 5, 2016</start_date>
    <completion_date type="Anticipated">December 5, 2023</completion_date>
    <primary_completion_date type="Anticipated">December 5, 2023</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>Description of the natural course of vascular Ehlers-Danlos syndrome (vEDS) based on anatomical criteria (number and type of arterial lesions or angioscanner or MRI)</measure>
      <time_frame>Through study completion, an average of 3 years</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Description of the natural course of vascular Ehlers-Danlos syndrome (vEDS) based on functional criteria (spontaneous arterial, digestive, obstetrical and pulmonary events)</measure>
      <time_frame>Through study completion, an average of 3 years</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Description of the natural course of vascular Ehlers-Danlos syndrome (vEDS) based on surgical criteria (types and complications)</measure>
      <time_frame>Through study completion, an average of 3 years</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Description of the natural course of vascular Ehlers-Danlos syndrome (vEDS) based on evaluation of the quality of life (impact on daily life, social life and professional activity)</measure>
      <time_frame>Through study completion, an average of 3 years</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Description of the natural course of vascular Ehlers-Danlos syndrome (vEDS) based on evaluation of mortality (death, disability)</measure>
      <time_frame>Through study completion, an average of 3 years</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Description of the natural course of vascular Ehlers-Danlos syndrome (vEDS) based on the presence of complications at delivery or after C-section</measure>
      <time_frame>Through study completion, an average of 3 years</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Study of prospective genotype-phenotype relationships</measure>
      <time_frame>Through study completion, an average of 3 years</time_frame>
      <description>Mutations of the COL3A1 gene are stratified within 5 classes (Frank et al. Eur J Hum Genet 2015):&#xD;
  Glycine substitutions,&#xD;
  splice-site and in-frame insertions-deletions,&#xD;
  variants leading to haplo-insufficiency,&#xD;
  non-glycine missense variants within the triple helix,&#xD;
  non-glycine missense variants or in-frame insertions-deletions, in the N- or C-terminal part of the protein&#xD;
  An association study between the type of mutation in the COL3A1 gene (individually or combined in two groups: (a+b) versus (c+d+e)) and the clinical phenotype or co-factors of morbidity (medication, lifestyle, smoking, physical activity…) will be performed. This study will be based on explicative multivariate analysis (e.g.: PCA, Logistic regression, ect.) and relevant association will be quantified by the corresponding correlation coefficient.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Study of the intrafamilial phenotypes relationships</measure>
      <time_frame>Through study completion, an average of 3 years</time_frame>
      <description>This study will be based on an explicative multivariate analysis (eg: PCA, Logistic regression, ect.) and relevant associations will be quantified by the corresponding correlation coefficients. Distribution of clinical symptoms with a positive correlation with the family history, will be displayed and illustrated by appropriate graphic method (Bar chart, box plot, forest plot, etc.).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Evaluation of the global cost of vEDS cares</measure>
      <time_frame>Through study completion, an average of 3 years</time_frame>
      <description>The analysis of the global cost of vEDS cares will be detailed by type of expenditure. The average cost will be estimated with health-care payer's perspective, i.e. the French health insurance system.&#xD;
  After estimating the average global cost of vEDS cares, including both standard pathway's cost and vEDS' cost, a Tornado diagram will analyse the impact of the change of one or more parameters used in the analysis process. This will allow us to identify which parameters have an impact on the result by introducing uncertainties on values used. These parameters will vary in a range obtained by literature review, expert opinion or arbitrarily by simulation on a normal distribution.&#xD;
  All the results will be drafted in statistical medico-economic analysis report to be presented to all investigators at the end of the study.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Evaluation of the therapeutic management</measure>
      <time_frame>Through study completion, an average of 3 years</time_frame>
      <description>A descriptive analysis of the different types of medication (celiprolol alone or associated to another drug) and their association to disease progression and life style will be performed by evaluating the number of lesions and/or the increased severity of the lesions and/or the appearance of lesions at different anatomical site.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assessment of the correlation between the diffusion of arterial lesions and the occurrence of cardiovascular complication</measure>
      <time_frame>Through study completion, an average of 3 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assessment of the repercussions of vEDS on patients' quality of life evaluated through scores of quality of life questionnaire Short-Form Health Survey (SF-36)</measure>
      <time_frame>Through study completion, an average of 3 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assessment of the repercussions of vEDS on patients' quality of life evaluated through scores of quality of life questionnaire Short-Form Health Survey (SF-10)</measure>
      <time_frame>Through study completion, an average of 3 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assessment of the repercussions of vEDS on patients' quality of life evaluated through scores of quality of life questionnaire HADS</measure>
      <time_frame>Through study completion, an average of 3 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assessment of the repercussions of vEDS on patients' quality of life evaluated through scores of quality of life questionnaire socio-professional life</measure>
      <time_frame>Through study completion, an average of 3 years</time_frame>
    </secondary_outcome>
    <enrollment type="Anticipated">340</enrollment>
    <condition>Ehlers-Danlos Syndrome, Vascular Type</condition>
    <eligibility>
      <study_pop>
        <textblock>
          Patients diagnosed as vEDS on a positive genetic testing on the COL3A1 gene.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Patients eligible for inclusion in this study have to fulfil all of the following criteria:&#xD;
  &#xD;
            -  Patients (adults and children) with genetically-proven vEDS (presence of a pathogenic&#xD;
               mutation at the COL3A1 gene);&#xD;
  &#xD;
            -  Patients (or his/her legal guardian) who does not oppose to his/her personal data&#xD;
               collection.&#xD;
  &#xD;
          There are no exclusion criteria for this 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>Xavier JEUNEMAITRE</last_name>
      <role>Principal Investigator</role>
      <affiliation>INSERM UMR S970</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Xavier JEUNEMAITRE</last_name>
      <phone>01 56 09 38 81</phone>
      <email>xavier.jeunemaitre@aphp.fr</email>
    </overall_contact>
    <location>
      <facility>
        <name>Centre Hospitalier Universitaire Angers</name>
        <address>
          <city>Angers</city>
          <country>France</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Carmen Cristina BELIZNA SCHWED</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hôpital Saint-André</name>
        <address>
          <city>Bordeaux</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Joël CONSTANS</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hôpital de la Cavale Blanche</name>
        <address>
          <city>Brest</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Luc BRESSOLLETTE</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hôpital Côte de Nacre</name>
        <address>
          <city>Caen</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Damien LANEELLE</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hôpital Gabriel Montpied</name>
        <address>
          <city>Clermont-Ferrand</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Hélène THIEL</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hôpital Michallon</name>
        <address>
          <city>Grenoble</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Christophe SEINTURIER</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hôpital Claude Huriez</name>
        <address>
          <city>Lille</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Marc LAMBERT</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hôpital Edouard Herriot</name>
        <address>
          <city>Lyon</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Arnaud HOT</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hôpital Femme Mère Enfant</name>
        <address>
          <city>Lyon</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Sophie DUPUIS-GIROD</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hôpital de la Timone</name>
        <address>
          <city>Marseille</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Laurence BAL-THEOLEYRE</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hôpital Saint-Eloi</name>
        <address>
          <city>Montpellier</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Isabelle QUERE</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hôpital Brabois</name>
        <address>
          <city>Nancy</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Denis WAHL</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hôpital Hôtel Dieu</name>
        <address>
          <city>Nantes</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Marc-Antoine PISTORIUS</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hôpital Européen Georges Pompidou</name>
        <address>
          <city>Paris</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Xavier JEUNEMAITRE</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hôpital Nord</name>
        <address>
          <city>Saint-Étienne</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Claire LE HELLO</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hôpital Rangueil</name>
        <address>
          <city>Toulouse</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Alessandra BURA-RIVIERE</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hôpital Trousseau</name>
        <address>
          <city>Tours</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Gabriella GEORGESCOU</last_name>
      </contact>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 18, 2023</study_first_submitted>
    <study_first_submitted_qc>July 26, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>July 26, 2023</last_update_submitted>
    <last_update_submitted_qc>July 26, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Ehlers-Danlos Syndrome</mesh_term>
      <mesh_term>Ehlers-Danlos Syndrome, Type IV</mesh_term>
      <mesh_term>Syndrome</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05976841
  org study id: C15-65
  nct id: NCT05976841
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this observational study is to describe the natural course of vascular
        Ehlers-Danlos syndrome, in particular the order of appearance of different types of
        complications (arterial, digestive, pulmonary and uterine).
  observational model: Cohort
  time perspective: Other
  measure: Description of the natural course of vascular Ehlers-Danlos syndrome (vEDS) based on anatomical criteria (number and type of arterial lesions or angioscanner or MRI)
  time frame: Through study completion, an average of 3 years
  measure: Description of the natural course of vascular Ehlers-Danlos syndrome (vEDS) based on functional criteria (spontaneous arterial, digestive, obstetrical and pulmonary events)
  time frame: Through study completion, an average of 3 years
  measure: Description of the natural course of vascular Ehlers-Danlos syndrome (vEDS) based on surgical criteria (types and complications)
  time frame: Through study completion, an average of 3 years
  measure: Description of the natural course of vascular Ehlers-Danlos syndrome (vEDS) based on evaluation of the quality of life (impact on daily life, social life and professional activity)
  time frame: Through study completion, an average of 3 years
  measure: Description of the natural course of vascular Ehlers-Danlos syndrome (vEDS) based on evaluation of mortality (death, disability)
  time frame: Through study completion, an average of 3 years
  measure: Description of the natural course of vascular Ehlers-Danlos syndrome (vEDS) based on the presence of complications at delivery or after C-section
  time frame: Through study completion, an average of 3 years
  measure: Study of prospective genotype-phenotype relationships
  time frame: Through study completion, an average of 3 years
  description: Mutations of the COL3A1 gene are stratified within 5 classes (Frank et al. Eur J Hum Genet 2015):
  Glycine substitutions,
  splice-site and in-frame insertions-deletions,
  variants leading to haplo-insufficiency,
  non-glycine missense variants within the triple helix,
  non-glycine missense variants or in-frame insertions-deletions, in the N- or C-terminal part of the protein
  An association study between the type of mutation in the COL3A1 gene (individually or combined in two groups: (a+b) versus (c+d+e)) and the clinical phenotype or co-factors of morbidity (medication, lifestyle, smoking, physical activity…) will be performed. This study will be based on explicative multivariate analysis (e.g.: PCA, Logistic regression, ect.) and relevant association will be quantified by the corresponding correlation coefficient.
  measure: Study of the intrafamilial phenotypes relationships
  time frame: Through study completion, an average of 3 years
  description: This study will be based on an explicative multivariate analysis (eg: PCA, Logistic regression, ect.) and relevant associations will be quantified by the corresponding correlation coefficients. Distribution of clinical symptoms with a positive correlation with the family history, will be displayed and illustrated by appropriate graphic method (Bar chart, box plot, forest plot, etc.).
  measure: Evaluation of the global cost of vEDS cares
  time frame: Through study completion, an average of 3 years
  description: The analysis of the global cost of vEDS cares will be detailed by type of expenditure. The average cost will be estimated with health-care payer's perspective, i.e. the French health insurance system.
  After estimating the average global cost of vEDS cares, including both standard pathway's cost and vEDS' cost, a Tornado diagram will analyse the impact of the change of one or more parameters used in the analysis process. This will allow us to identify which parameters have an impact on the result by introducing uncertainties on values used. These parameters will vary in a range obtained by literature review, expert opinion or arbitrarily by simulation on a normal distribution.
  All the results will be drafted in statistical medico-economic analysis report to be presented to all investigators at the end of the study.
  measure: Evaluation of the therapeutic management
  time frame: Through study completion, an average of 3 years
  description: A descriptive analysis of the different types of medication (celiprolol alone or associated to another drug) and their association to disease progression and life style will be performed by evaluating the number of lesions and/or the increased severity of the lesions and/or the appearance of lesions at different anatomical site.
  measure: Assessment of the correlation between the diffusion of arterial lesions and the occurrence of cardiovascular complication
  time frame: Through study completion, an average of 3 years
  measure: Assessment of the repercussions of vEDS on patients' quality of life evaluated through scores of quality of life questionnaire Short-Form Health Survey (SF-36)
  time frame: Through study completion, an average of 3 years
  measure: Assessment of the repercussions of vEDS on patients' quality of life evaluated through scores of quality of life questionnaire Short-Form Health Survey (SF-10)
  time frame: Through study completion, an average of 3 years
  measure: Assessment of the repercussions of vEDS on patients' quality of life evaluated through scores of quality of life questionnaire HADS
  time frame: Through study completion, an average of 3 years
  measure: Assessment of the repercussions of vEDS on patients' quality of life evaluated through scores of quality of life questionnaire socio-professional life
  time frame: Through study completion, an average of 3 years
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: N/A
  maximum age: N/A
  healthy volunteers: No
  last name: Xavier JEUNEMAITRE
  role: Principal Investigator
  affiliation: INSERM UMR S970
  last name: Xavier JEUNEMAITRE
  phone: 01 56 09 38 81
  email: xavier.jeunemaitre@aphp.fr
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
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  status: Recruiting
  contact: 
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  status: Recruiting
  contact: 
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  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  country: France
  responsible party type: Sponsor
  mesh term: Ehlers-Danlos Syndrome
  mesh term: Ehlers-Danlos Syndrome, Type IV
  mesh term: Syndrome
  sharing ipd: No