<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/NCT02976714</url>
  </required_header>
  <id_info>
    <org_study_id>UF9745</org_study_id>
    <nct_id>NCT02976714</nct_id>
  </id_info>
  <brief_title>Identification of Predictive Epigenetic Biomarkers of Lung Disease Severity in Cystic Fibrosis</brief_title>
  <acronym>MethylBiomark</acronym>
  <official_title>Identification of Predictive Epigenetic Biomarkers of Lung Disease Severity in Cystic Fibrosis</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>Yes</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 general aims of this project are (i) to identify predictive epigenetic biomarkers of lung&#xD;
      disease severity in Cystic Fibrosis, (ii) to characterize a non-invasive cellular model,&#xD;
      spontaneous sputum, for the analysis of these epigenetic biomarkers, (iii) to analyze the&#xD;
      variations in DNA methylation for a same patient over time.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cystic Fibrosis (CF) is an autosomal recessive disease resulting from mutations in the CFTR&#xD;
      gene. CFTR encodes a chloride channel, mainly expressed at the apical membrane of epithelial&#xD;
      cells. CFTR dysfunction induces mucus thickening, causing multiple disorders in respiratory,&#xD;
      digestive and reproductive tracts. In CF patients, lung disease is the main cause of&#xD;
      morbidity and mortality, and its severity is variable among CF patients, even among those&#xD;
      with the same genotype. This clinical variability depends on two factors: genetic (complex&#xD;
      alleles of CFTR gene and modifier genes) and environmental factors. Genetic factors have been&#xD;
      largely explored, and several modifier genes have been identified. By contrast, environmental&#xD;
      factors are still poorly known. It is well established that environmental factors modify the&#xD;
      phenotype by acting on epigenetic marks (i.e. DNA methylation, histone modification) present&#xD;
      in the genome. Epigenetic modifications regulate and modulate gene expression.&#xD;
&#xD;
      In a previous we profiled DNA methylation genome-wide in nasal epithelial cell samples from&#xD;
      32 CF patients and 24 healthy controls. CF patients homozygous for the p.Phe508del mutation&#xD;
      and &gt;18-years-old were stratified according to the lung disease severity. Through this study,&#xD;
      we identified 187 genomic regions (CpG dinucleotides) differentially methylated between CF&#xD;
      patients with mild lung disease and CF patients with severe lung disease. The present project&#xD;
      aims at identifying predictive epigenetic biomarkers of lung disease severity, among these&#xD;
      187 regions. While the previous study was carried out on genomic DNA extracted from nasal&#xD;
      epithelial cells, in the present project we will use a non-invasive model: spontaneous&#xD;
      sputum.&#xD;
&#xD;
      Hypothesis: some differentially methylated genomic regions between mild and severe CF&#xD;
      patients can be used as predictive epigenetic biomarkers of lung disease severity in cystic&#xD;
      fibrosis.&#xD;
&#xD;
      Objectives: (i) to identify predictive epigenetic biomarkers of lung disease severity among&#xD;
      the differentially methylated genomic regions between mild and severe CF patients, (ii) to&#xD;
      characterize a non-invasive cellular model, spontaneous sputum, for the analysis of&#xD;
      epigenetic biomarkers of lung disease severity in CF, (iii) to analyze the variations in DNA&#xD;
      methylation for a same patient over time (at time of inclusion, 6 months, 12 months and 18&#xD;
      months)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 12, 2016</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>DNA methylation</measure>
    <time_frame>at time of inclusion</time_frame>
    <description>Spontaneous expectoration at baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>DNA methylation</measure>
    <time_frame>6 months</time_frame>
    <description>Spontaneous expectoration at 6 months</description>
  </primary_outcome>
  <primary_outcome>
    <measure>DNA methylation</measure>
    <time_frame>12 months</time_frame>
    <description>Spontaneous expectoration at 12 months</description>
  </primary_outcome>
  <primary_outcome>
    <measure>DNA methylation</measure>
    <time_frame>18 months</time_frame>
    <description>Spontaneous expectoration at 18 months</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>CF patients</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>CF patients carry a spontaneous sputum that is made in the context of bronchial drainage sessions conducted as part of usual care.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>spontaneous sputum</intervention_name>
    <description>CF patients carry a spontaneous sputum that is made in the context of bronchial drainage sessions conducted as part of usual care (inclusion, 6 months, 12 months, 18 months).&#xD;
The collection of spontaneous sputum is carried out within the bronchial drainage sessions, which are routinely performed at each visit. The spontaneous sputum is collected in a sterile container. In order not to contaminate the sputum with buccal epithelial cells will be asked patients to rinse the mouth before expectorate.</description>
    <arm_group_label>CF patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  free and informed consent obtained, and consent signed&#xD;
&#xD;
          -  subject covered by a state insurance scheme&#xD;
&#xD;
          -  women and men aged 12 to 30&#xD;
&#xD;
          -  subject affected by cystic fibrosis, carrier of two severe mutations in trans (in the&#xD;
             same allele) in the CFTR gene&#xD;
&#xD;
          -  subject able to realize a spirometry before and during the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  subject in an exclusion period of a previous study&#xD;
&#xD;
          -  subject placed under judicial protection, guardianship or supervision&#xD;
&#xD;
          -  impossibility to give informed information to the subject&#xD;
&#xD;
          -  subject who does not read fluently French&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  breastfeeding&#xD;
&#xD;
          -  transplanted subject&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Davide CAIMMI</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Montpellier</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Uhmontpellier</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>November 8, 2016</study_first_submitted>
  <study_first_submitted_qc>November 24, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>October 27, 2021</last_update_submitted>
  <last_update_submitted_qc>October 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cystic Fibrosis</keyword>
  <keyword>Lung disease</keyword>
  <keyword>DNA methylation</keyword>
  <keyword>Predictive biomarkers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Fibrosis</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/NCT02976714
org study id: UF9745
nct id: NCT02976714
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The general aims of this project are (i) to identify predictive epigenetic biomarkers of lung
      disease severity in Cystic Fibrosis, (ii) to characterize a non-invasive cellular model,
      spontaneous sputum, for the analysis of these epigenetic biomarkers, (iii) to analyze the
      variations in DNA methylation for a same patient over time.
Cystic Fibrosis (CF) is an autosomal recessive disease resulting from mutations in the CFTR
      gene. CFTR encodes a chloride channel, mainly expressed at the apical membrane of epithelial
      cells. CFTR dysfunction induces mucus thickening, causing multiple disorders in respiratory,
      digestive and reproductive tracts. In CF patients, lung disease is the main cause of
      morbidity and mortality, and its severity is variable among CF patients, even among those
      with the same genotype. This clinical variability depends on two factors: genetic (complex
      alleles of CFTR gene and modifier genes) and environmental factors. Genetic factors have been
      largely explored, and several modifier genes have been identified. By contrast, environmental
      factors are still poorly known. It is well established that environmental factors modify the
      phenotype by acting on epigenetic marks (i.e. DNA methylation, histone modification) present
      in the genome. Epigenetic modifications regulate and modulate gene expression.

      In a previous we profiled DNA methylation genome-wide in nasal epithelial cell samples from
      32 CF patients and 24 healthy controls. CF patients homozygous for the p.Phe508del mutation
      and >18-years-old were stratified according to the lung disease severity. Through this study,
      we identified 187 genomic regions (CpG dinucleotides) differentially methylated between CF
      patients with mild lung disease and CF patients with severe lung disease. The present project
      aims at identifying predictive epigenetic biomarkers of lung disease severity, among these
      187 regions. While the previous study was carried out on genomic DNA extracted from nasal
      epithelial cells, in the present project we will use a non-invasive model: spontaneous
      sputum.

      Hypothesis: some differentially methylated genomic regions between mild and severe CF
      patients can be used as predictive epigenetic biomarkers of lung disease severity in cystic
      fibrosis.

      Objectives: (i) to identify predictive epigenetic biomarkers of lung disease severity among
      the differentially methylated genomic regions between mild and severe CF patients, (ii) to
      characterize a non-invasive cellular model, spontaneous sputum, for the analysis of
      epigenetic biomarkers of lung disease severity in CF, (iii) to analyze the variations in DNA
      methylation for a same patient over time (at time of inclusion, 6 months, 12 months and 18
      months)
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: DNA methylation
time frame: at time of inclusion
description: Spontaneous expectoration at baseline
measure: DNA methylation
time frame: 6 months
description: Spontaneous expectoration at 6 months
measure: DNA methylation
time frame: 12 months
description: Spontaneous expectoration at 12 months
measure: DNA methylation
time frame: 18 months
description: Spontaneous expectoration at 18 months
arm group label: CF patients
arm group type: Other
description: CF patients carry a spontaneous sputum that is made in the context of bronchial drainage sessions conducted as part of usual care.
intervention type: Other
intervention name: spontaneous sputum
description: CF patients carry a spontaneous sputum that is made in the context of bronchial drainage sessions conducted as part of usual care (inclusion, 6 months, 12 months, 18 months).
The collection of spontaneous sputum is carried out within the bronchial drainage sessions, which are routinely performed at each visit. The spontaneous sputum is collected in a sterile container. In order not to contaminate the sputum with buccal epithelial cells will be asked patients to rinse the mouth before expectorate.
arm group label: CF patients
criteria: 
gender: All
minimum age: 12 Years
maximum age: 30 Years
healthy volunteers: No
last name: Davide CAIMMI
role: Principal Investigator
affiliation: University Hospital, Montpellier
facility: 
country: France
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Lung Diseases
mesh term: Fibrosis
sharing ipd: Undecided