<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/NCT03298321</url>
  </required_header>
  <id_info>
    <org_study_id>69HCL17_0114</org_study_id>
    <nct_id>NCT03298321</nct_id>
  </id_info>
  <brief_title>Action of the Vidaza on the Atrial Fibrillation</brief_title>
  <acronym>AVIFA</acronym>
  <official_title>Action of the Vidaza on the Atrial Fibrillation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospices Civils de Lyon</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>
      Genomic studies on atrial fibrillation patients have identified polymorphisms in regions&#xD;
      surrounding the PITX2 gene, suggesting it could be the locus responsible for atrial&#xD;
      fibrillation. The PITX2 gene is essential for establishing the asymmetry between systemic and&#xD;
      pulmonary blood flow, which is absolutely required for proper heart functions. In addition,&#xD;
      PITX2 is required for the development the atrium myocardium. Investigators have performed&#xD;
      transcriptomic analysis on left atrium tissues from atrial fibrillation patients and identify&#xD;
      genes whose expression is altered in atrial fibrillation. Among affected genes, PITX2&#xD;
      expression is strongly decreased in the left atrium of atrial fibrillation patients.&#xD;
      Moreover, investigators observed that the PITX2 promoter region is hypermethylated in atrial&#xD;
      fibrillation patients. Interestingly, DNA methylation is a key actor of gene expression and&#xD;
      directly regulates RNA transcription either by directly modulating transcription factor (TF)&#xD;
      binding to gene promoters or by modifying local chromatin structures, therefore limiting&#xD;
      access of TFs to DNA. These epigenetic modifications are reversible and therefore represent&#xD;
      an interesting therapeutic target. Hence, many compounds that inhibit DNA methyl-transferase&#xD;
      are currently tested in different disease models. Recently-designed hypomethylating molecules&#xD;
      are available, such as the 5'azacytidine (Vidaza®, Celgen Inc.) or the 5-aza-2'-deoxycytidine&#xD;
      (Decitabine) (Dacogen®, Janssen Cilag). Investigators have performed preliminary studies on&#xD;
      the effect of Decitabine on DNA methylation and proper cardiac function recovering in a SHR&#xD;
      model. Results indicate that the chronic delivery of Decitabine improves the arrhythmia&#xD;
      profile by reducing tachyarrhythmia, fibrosis, as well as the oxidative stress in SHR left&#xD;
      atrium submitted Acute Leukemia is a rare pathology with an incidence of 4 per 100,000 in&#xD;
      France. Azacytidine, which is closely related to Decitabine, is commonly used for treating&#xD;
      Acute Leukemia and possesses anti-neoplastic effect through multiple mechanisms, including&#xD;
      direct cytotoxicity of blood cancer cells and DNA hypomethylation. The goal of this study is&#xD;
      to evaluate the effects of azacytidine on arrhythmia and left atrium fibrosis as well, which&#xD;
      are the two mains phenotypic manifestation of atrial fibrillation in humans. Investigators&#xD;
      hypothesize that azacytidine decreases PITX2 promoter methylation and increases PITX2&#xD;
      expression. Hence, investigators expect to ameliorate the duration of atrium action potential&#xD;
      and to observe a decrease of atrium fibrosis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 20, 2018</start_date>
  <completion_date type="Anticipated">December 20, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 20, 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>Evolution of atrial arrhythmic events</measure>
    <time_frame>Maximum 12 months</time_frame>
    <description>Evolution of the atrial arrhythmic events observed in the inclusion, 6 months or 12 months (according to the frequency of follow-up of the atrial fibrillation) after the beginning of the cure by Holter-ECG.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evolution of the morphology and the fibrosis atrial</measure>
    <time_frame>Maximum 12 months</time_frame>
    <description>Evolution of the morphology and the fibrosis atrial observed in the inclusion, 6 months or 12 months (according to the frequency of follow-up of the atrial fibrillation) after the beginning of the cure by transthoracic echocardiography.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">14</enrollment>
  <condition>Atrial Fibrillation</condition>
  <condition>Acute Leukemia</condition>
  <arm_group>
    <arm_group_label>Vidaza patients</arm_group_label>
    <description>This study will be performed on adults with Acute Myeloid Leukemia and atrial fibrillation. Only patients treated for the first time with vidaza® within an hospital hematology unit will be included.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Effect of Vidaza treatment</intervention_name>
    <description>The goal of this study is to evaluate the effects of azacytidine on arrhythmia and left atrium fibrosis.</description>
    <arm_group_label>Vidaza patients</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        This study will be performed on adults with Acute Myeloid Leukemia and atrial fibrillation.&#xD;
        Only patients treated for the first time with vidaza® within an hospital hematology unit&#xD;
        will be included.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years old&#xD;
&#xD;
          -  Patient with history of paroxysmal atrial fibrillation, and /or presenting a&#xD;
             dilatation of the left atrium.&#xD;
&#xD;
          -  Patient selected for a first Vidaza® treatment&#xD;
&#xD;
          -  Non-opposition of the patient to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 18 years old&#xD;
&#xD;
          -  No paroxysmal atrial fibrillation&#xD;
&#xD;
          -  Patients with previous history of Vidaza® treatment&#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>Philippe CHEVALIER, MD</last_name>
    <phone>04 72 35 76 89</phone>
    <phone_ext>+33</phone_ext>
    <email>philippe.chavalier@chu-lyon.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Camille VALLA</last_name>
    <phone>04 27 85 62 69</phone>
    <phone_ext>+33</phone_ext>
    <email>camille.valla@chu-lyon.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Service de rythmologie - GH Est-Hôpital Louis Pradel - CHU de Lyon HCL</name>
      <address>
        <city>Bron</city>
        <zip>69229</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Philippe CHEVALIER, MD</last_name>
      <phone>04 72 35 76 89</phone>
      <phone_ext>+33</phone_ext>
      <email>philippe.chavalier@chu-lyon.fr</email>
    </contact>
    <contact_backup>
      <last_name>Camille VALLA</last_name>
      <phone>04 27 85 62 69</phone>
      <phone_ext>+33</phone_ext>
      <email>camille.valla@chu-lyon.fr</email>
    </contact_backup>
    <investigator>
      <last_name>Philippe CHEVALIER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Léon Berard</name>
      <address>
        <city>Lyon</city>
        <zip>69008</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anne-Sophie Michallet, MD, PhD</last_name>
      <phone>04.78.78.26.41</phone>
      <phone_ext>+33</phone_ext>
      <email>anne-sophie.michallet@lyon.unicancer.fr</email>
    </contact>
    <investigator>
      <last_name>Anne-Sophie Michallet, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hopital Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <zip>69310</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pierre-Yves COURAND, MD, PhD</last_name>
      <phone>04.78.86.57.37</phone>
      <phone_ext>+33</phone_ext>
      <email>pierre-yves.courand@chu-lyon.fr</email>
    </contact>
    <contact_backup>
      <last_name>Fiorenza Barraco, MD, PhD</last_name>
      <phone>04.78.86.43.40</phone>
      <phone_ext>+33</phone_ext>
      <email>fiorenza.barraco@chu-lyon.fr</email>
    </contact_backup>
    <investigator>
      <last_name>Pierre-Yves COURAND, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Fiorenza Barraco, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>September 27, 2017</study_first_submitted>
  <study_first_submitted_qc>September 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 2, 2017</study_first_posted>
  <last_update_submitted>October 15, 2019</last_update_submitted>
  <last_update_submitted_qc>October 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 16, 2019</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>Atrial Fibrillation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Azacitidine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03298321
org study id: 69HCL17_0114
nct id: NCT03298321
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Genomic studies on atrial fibrillation patients have identified polymorphisms in regions
      surrounding the PITX2 gene, suggesting it could be the locus responsible for atrial
      fibrillation. The PITX2 gene is essential for establishing the asymmetry between systemic and
      pulmonary blood flow, which is absolutely required for proper heart functions. In addition,
      PITX2 is required for the development the atrium myocardium. Investigators have performed
      transcriptomic analysis on left atrium tissues from atrial fibrillation patients and identify
      genes whose expression is altered in atrial fibrillation. Among affected genes, PITX2
      expression is strongly decreased in the left atrium of atrial fibrillation patients.
      Moreover, investigators observed that the PITX2 promoter region is hypermethylated in atrial
      fibrillation patients. Interestingly, DNA methylation is a key actor of gene expression and
      directly regulates RNA transcription either by directly modulating transcription factor (TF)
      binding to gene promoters or by modifying local chromatin structures, therefore limiting
      access of TFs to DNA. These epigenetic modifications are reversible and therefore represent
      an interesting therapeutic target. Hence, many compounds that inhibit DNA methyl-transferase
      are currently tested in different disease models. Recently-designed hypomethylating molecules
      are available, such as the 5'azacytidine (Vidaza®, Celgen Inc.) or the 5-aza-2'-deoxycytidine
      (Decitabine) (Dacogen®, Janssen Cilag). Investigators have performed preliminary studies on
      the effect of Decitabine on DNA methylation and proper cardiac function recovering in a SHR
      model. Results indicate that the chronic delivery of Decitabine improves the arrhythmia
      profile by reducing tachyarrhythmia, fibrosis, as well as the oxidative stress in SHR left
      atrium submitted Acute Leukemia is a rare pathology with an incidence of 4 per 100,000 in
      France. Azacytidine, which is closely related to Decitabine, is commonly used for treating
      Acute Leukemia and possesses anti-neoplastic effect through multiple mechanisms, including
      direct cytotoxicity of blood cancer cells and DNA hypomethylation. The goal of this study is
      to evaluate the effects of azacytidine on arrhythmia and left atrium fibrosis as well, which
      are the two mains phenotypic manifestation of atrial fibrillation in humans. Investigators
      hypothesize that azacytidine decreases PITX2 promoter methylation and increases PITX2
      expression. Hence, investigators expect to ameliorate the duration of atrium action potential
      and to observe a decrease of atrium fibrosis.
observational model: Cohort
time perspective: Prospective
measure: Evolution of atrial arrhythmic events
time frame: Maximum 12 months
description: Evolution of the atrial arrhythmic events observed in the inclusion, 6 months or 12 months (according to the frequency of follow-up of the atrial fibrillation) after the beginning of the cure by Holter-ECG.
measure: Evolution of the morphology and the fibrosis atrial
time frame: Maximum 12 months
description: Evolution of the morphology and the fibrosis atrial observed in the inclusion, 6 months or 12 months (according to the frequency of follow-up of the atrial fibrillation) after the beginning of the cure by transthoracic echocardiography.
arm group label: Vidaza patients
description: This study will be performed on adults with Acute Myeloid Leukemia and atrial fibrillation. Only patients treated for the first time with vidaza® within an hospital hematology unit will be included.
intervention type: Other
intervention name: Effect of Vidaza treatment
description: The goal of this study is to evaluate the effects of azacytidine on arrhythmia and left atrium fibrosis.
arm group label: Vidaza patients
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Philippe CHEVALIER, MD
phone: 04 72 35 76 89
phone ext: +33
email: philippe.chavalier@chu-lyon.fr
last name: Camille VALLA
phone: 04 27 85 62 69
phone ext: +33
email: camille.valla@chu-lyon.fr
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Atrial Fibrillation
mesh term: Azacitidine
sharing ipd: No