<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/NCT01707563</url>
  </required_header>
  <id_info>
    <org_study_id>P071009</org_study_id>
    <nct_id>NCT01707563</nct_id>
  </id_info>
  <brief_title>Clinical Variability in Marfan Syndrome</brief_title>
  <acronym>Variarfan</acronym>
  <official_title>Correlations' Study Between Variability of Expression in FBN1 Gene and Clinical Features in Marfan Patients.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Banque de cellules cochin</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Marfan syndrome is an autosomal dominant connective tissue disorder caused by mutations in&#xD;
      the fibrillin-1 gene (FBN1). Penetrance of FBN1 mutations is complete but intra and inter&#xD;
      familial clinical expressivity is extremely variable. The underlying mechanisms for&#xD;
      variability are not understood. An interesting mechanism is that the expression level of the&#xD;
      wild type and/or mutated allele may play a role in the determination of variability.&#xD;
&#xD;
      Principal objective: To evaluate in Marfan patients, if FBN1 expression level (non-mutated or&#xD;
      mutated allele) modulates the clinical expression of the disease.&#xD;
&#xD;
      Judgment criteria : Correlation allelic expression level-phenotype Perspectives : To search&#xD;
      the predictive factors of severity in order to ameliorate precocity of taking care.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Marfan syndrome is an autosomal dominant connective tissue disorder caused by mutations in&#xD;
      the fibrillin-1 gene (FBN1). Penetrance of FBN1 mutations is complete but intra and inter&#xD;
      familial clinical expressivity is extremely variable. The underlying mechanisms for&#xD;
      variability are not understood. An interesting mechanism is that the expression level of the&#xD;
      wild type and/or mutated allele may play a role in the determination of variability.&#xD;
&#xD;
      Principal objective : To evaluate in Marfan patients, if FBN1 expression level (non-mutated&#xD;
      or mutated allele) modulates the clinical expression of the disease in individuals from&#xD;
      families with clinical variability (intrafamilial) and in independant probands&#xD;
      (interfamilial).&#xD;
&#xD;
      Judgment criteria : Correlation allelic expression level-phenotype Method : In Marfan&#xD;
      patients with a FBN1 nul allele, FBN1 RNA will be extracted from a fibroblast culture.&#xD;
      Allelic FBN1 expression level will be performed by quantitative RT-PCR and then compared with&#xD;
      clinical evaluation.&#xD;
&#xD;
      Number of subjects : 160 subjects, 45 Marfan patients in 15 independent families, 5 patients&#xD;
      with the same mutation, 30 with a private mutation leading to a nul allele and 80 non Marfan&#xD;
      subjects.&#xD;
&#xD;
      Perspectives : To search the predictive factors of severity in order to ameliorate precocity&#xD;
      of taking care.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2009</start_date>
  <completion_date type="Actual">January 2012</completion_date>
  <primary_completion_date type="Actual">June 2011</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>FBN1 expression level</measure>
    <time_frame>6 months</time_frame>
    <description>Evaluation in Marfan patients, of FBN1 expression level (non-mutated or mutated allele) compared to the clinical expression of the disease in idividuals</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">160</enrollment>
  <condition>Marfan Syndrome</condition>
  <arm_group>
    <arm_group_label>Marfan patients</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Study participants were recruited between 11/2009 and 10/2011, among adult patients consulting in the Multidisciplinary Marfan Clinic of our University Hospital, and having a known mutation in the FBN1 gene. There, patients are evaluated by geneticists, rheumatologists, cardiologists, and ophthalmologists. Systematic slit-lamp examination, cardiac ultrasonography, and radiological investigations are also performed. A skin punch biopsy was used to establish a fibroblast cell culture. We determined mRNA levels for FBN1 and compared it to the clinical involvement.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control patients</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Fibroblasts were obtained from non Marfan patients (cell bank). We determineed mRNA level for FBN1 for each allele.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>skin punch biopsy and molecular biology</intervention_name>
    <arm_group_label>Marfan patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>fibroblast culture and molecular biology</intervention_name>
    <arm_group_label>control patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Man or woman &gt; 18 years old&#xD;
&#xD;
          -  With a mutation in FBN1 gene&#xD;
&#xD;
          -  Has signed an informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        -No affiliated to a Healthcare System.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chantal Stheneur, PHD, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hôpital Bichat, AP-HP</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre de Reference Maladie de Marfan Et Apparente</name>
      <address>
        <city>Paris</city>
        <state>Ile de France</state>
        <zip>75018</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>December 2010</verification_date>
  <study_first_submitted>October 12, 2012</study_first_submitted>
  <study_first_submitted_qc>October 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 16, 2012</study_first_posted>
  <last_update_submitted>November 5, 2014</last_update_submitted>
  <last_update_submitted_qc>November 5, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 6, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Marfan syndrome</keyword>
  <keyword>Variability</keyword>
  <keyword>Fibrillin 1</keyword>
  <keyword>clinical expression</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Marfan Syndrome</mesh_term>
    <mesh_term>Arachnodactyly</mesh_term>
    <mesh_term>Syndrome</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/NCT01707563
org study id: P071009
nct id: NCT01707563
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Marfan syndrome is an autosomal dominant connective tissue disorder caused by mutations in
      the fibrillin-1 gene (FBN1). Penetrance of FBN1 mutations is complete but intra and inter
      familial clinical expressivity is extremely variable. The underlying mechanisms for
      variability are not understood. An interesting mechanism is that the expression level of the
      wild type and/or mutated allele may play a role in the determination of variability.

      Principal objective: To evaluate in Marfan patients, if FBN1 expression level (non-mutated or
      mutated allele) modulates the clinical expression of the disease.

      Judgment criteria : Correlation allelic expression level-phenotype Perspectives : To search
      the predictive factors of severity in order to ameliorate precocity of taking care.
Marfan syndrome is an autosomal dominant connective tissue disorder caused by mutations in
      the fibrillin-1 gene (FBN1). Penetrance of FBN1 mutations is complete but intra and inter
      familial clinical expressivity is extremely variable. The underlying mechanisms for
      variability are not understood. An interesting mechanism is that the expression level of the
      wild type and/or mutated allele may play a role in the determination of variability.

      Principal objective : To evaluate in Marfan patients, if FBN1 expression level (non-mutated
      or mutated allele) modulates the clinical expression of the disease in individuals from
      families with clinical variability (intrafamilial) and in independant probands
      (interfamilial).

      Judgment criteria : Correlation allelic expression level-phenotype Method : In Marfan
      patients with a FBN1 nul allele, FBN1 RNA will be extracted from a fibroblast culture.
      Allelic FBN1 expression level will be performed by quantitative RT-PCR and then compared with
      clinical evaluation.

      Number of subjects : 160 subjects, 45 Marfan patients in 15 independent families, 5 patients
      with the same mutation, 30 with a private mutation leading to a nul allele and 80 non Marfan
      subjects.

      Perspectives : To search the predictive factors of severity in order to ameliorate precocity
      of taking care.
allocation: Non-Randomized
intervention model: Factorial Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: FBN1 expression level
time frame: 6 months
description: Evaluation in Marfan patients, of FBN1 expression level (non-mutated or mutated allele) compared to the clinical expression of the disease in idividuals
arm group label: Marfan patients
arm group type: Other
description: Study participants were recruited between 11/2009 and 10/2011, among adult patients consulting in the Multidisciplinary Marfan Clinic of our University Hospital, and having a known mutation in the FBN1 gene. There, patients are evaluated by geneticists, rheumatologists, cardiologists, and ophthalmologists. Systematic slit-lamp examination, cardiac ultrasonography, and radiological investigations are also performed. A skin punch biopsy was used to establish a fibroblast cell culture. We determined mRNA levels for FBN1 and compared it to the clinical involvement.
arm group label: control patients
arm group type: Other
description: Fibroblasts were obtained from non Marfan patients (cell bank). We determineed mRNA level for FBN1 for each allele.
intervention type: Procedure
intervention name: skin punch biopsy and molecular biology
arm group label: Marfan patients
intervention type: Other
intervention name: fibroblast culture and molecular biology
arm group label: control patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Chantal Stheneur, PHD, MD
role: Principal Investigator
affiliation: Hôpital Bichat, AP-HP
facility: 
country: France
responsible party type: Sponsor
mesh term: Marfan Syndrome
mesh term: Arachnodactyly
mesh term: Syndrome