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/NCT06022328</url>
    </required_header>
    <id_info>
      <org_study_id>CHUBX 2023/15</org_study_id>
      <nct_id>NCT06022328</nct_id>
    </id_info>
    <brief_title>Impact of Epigenetic Age on Clinic-biological Presentation and Prognosis in Myeloproliferative Neoplasms Epigenetic Age in Myeloproliferative Neoplasms (EpiC)</brief_title>
    <acronym>EpiC</acronym>
    <official_title>Impact of Epigenetic Age on Clinic-biological Presentation and Prognosis in Myeloproliferative Neoplasms Epigenetic Age in Myeloproliferative Neoplasms (EpiC)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospital, Bordeaux</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University Hospital, Bordeaux</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>
        Myeloproliferative Neoplasms (MPN) are hematological malignancies characterized by the&#xD;
        excessive production of myeloid cells. MPN can be complicated by thrombosis and evolution&#xD;
        into more aggressive diseases (myelofibrosis and acute leukemia). Aging remains the principal&#xD;
        factor determining patients' survival in MPN. In recent years, DNA methylation has appeared&#xD;
        as a mean to measure aging via the development of epigenetic clocks that have also been&#xD;
        associated with the occurrence of thrombosis and cancer. The epiC project aims at determining&#xD;
        epigenetic age of MPN patients and search for an association between this parameter and&#xD;
        thrombotic/hematological complications.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Myeloproliferative Neoplasia (MPN) are hematological malignancies characterized by the&#xD;
        excessive production of myeloid cells. They include Essential Thrombocythemia (ET),&#xD;
        Polycythemia Vera (VP) and Primary Myelofibrosis (PMF). Thrombosis are the most frequent&#xD;
        complications and are largely responsible for the morbidity and mortality observed in ET and&#xD;
        PV patients. The most feared complications are hematological transformations (into&#xD;
        myelofibrosis for PV and ET, into acute myeloid leukemia for PV, ET and PMF). The prognostic&#xD;
        assessment of MPN patients is mainly based on clinical data. Although recent studies have&#xD;
        shown that certain mutations are associated with a poorer prognosis, age remains the main&#xD;
        risk factor affecting survival in MPN patients. Recent studies have shown that DNA&#xD;
        methylation can be used to determine an &quot;epigenetic age&quot;. Interestingly, this epigenetic age&#xD;
        is associated with the development of cardiovascular disease and cancer.&#xD;
  &#xD;
        In this project, the epigenetic age of MPN patients will be determined by studying the DNA&#xD;
        methylation at diagnosis using the Infinium Human MethylationEPIC kit (Illumina). Epigenetic&#xD;
        age will be determined with the most commonly used epigenetic clocks (DNAmAge, DNAmHannum,&#xD;
        DNAmPhenoAge, DNAmSkinClock, DNAmGrimAge, intrinsic epigenetic age acceleration, extrinsic&#xD;
        epigenetic age acceleration). It will be searched for an association between accelerated&#xD;
        epigenetic aging (as assessed by the difference between epigenetic age and chronological age)&#xD;
        and the type of MPN, the clinical and biological presentation at diagnosis (including the&#xD;
        mutational profile of patients) and the occurrence of thrombosis and hematological evolution&#xD;
        into myelofibrosis and/or acute leukemia.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2024</completion_date>
    <primary_completion_date type="Anticipated">September 2024</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>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Accelerated ageing of patients</measure>
      <time_frame>At inclusion, up to 1 year after diagnosis</time_frame>
      <description>Accelerated ageing will be defined as an increased difference between the epigenetic age (calculated from DNA methylation data with the different molecular clocks described: DNAmAge, DNAmHannum, DNAmPhenoAge, DNAmSkinClock, DNAmGrimAge, intrinsic epigenetic age acceleration, extrinsic epigenetic age acceleration) and the chronological age</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Type of MPN (ET, PV or PMF) at diagnosis</measure>
      <time_frame>At inclusion, up to 1 year after diagnosis</time_frame>
      <description>We will study patients with a diagnosis of ET, PV or PMF as defined by the WHO classification of hematological malignancies</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Transformation into secondary myelofibrosis or acute leukemia</measure>
      <time_frame>From date of inclusion until documentation of the event, assessed up to 5 years</time_frame>
      <description>Evolution toward secondary myelofibrosis or acute leukemia will be defined according to the WHO classification of hematological malignancies</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Occurrence of thrombosis prior to diagnosis or during follow-up of the disease</measure>
      <time_frame>Between 1 year before and 2 years after MPN diagnosis</time_frame>
      <description>Occurrence of myocardial infarction, ischemic stroke, deep vein thrombosis, pulmonary embolism, splanchnic thrombosis or any other significant thrombosis. Tinnitus, vertigo, headaches, erythromelalgia as well as superficial vein thrombosis will not be considered as thrombotic events</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Leukocytes</measure>
      <time_frame>At inclusion, up to 1 year after diagnosis</time_frame>
      <description>Leukocytes level on blood count in G/L</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Platelets</measure>
      <time_frame>At inclusion, up to 1 year after diagnosis</time_frame>
      <description>Platelet level on blood count in G/L</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Granulocytes</measure>
      <time_frame>At inclusion, up to 1 year after diagnosis</time_frame>
      <description>Granulocytes level on blood count in G/L</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Monocytes</measure>
      <time_frame>At inclusion, up to 1 year after diagnosis</time_frame>
      <description>Monocytes level on blood count in G/L</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hemoglobin</measure>
      <time_frame>At inclusion, up to 1 year after diagnosis</time_frame>
      <description>Hemoglobin level on blood count in g/dL</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hematocrit</measure>
      <time_frame>At inclusion, up to 1 year after diagnosis</time_frame>
      <description>Hematocrit level on blood count in %</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Additional somatic mutation</measure>
      <time_frame>At inclusion, up to 1 year after diagnosis</time_frame>
      <description>In up to 50% of MPN patients, genetic variants can be detected in genes such as DNMT3A, TET2, ASXL1, SRSF2, SF3B1, U2AF1, EZH2 or TP53. We will determine which somatic genetic variant is detected by high throughput sequencing</description>
    </secondary_outcome>
    <number_of_groups>4</number_of_groups>
    <enrollment type="Anticipated">120</enrollment>
    <condition>Myeloproliferative Neoplasm</condition>
    <arm_group>
      <arm_group_label>Patients with ET</arm_group_label>
      <description>45 patients with ET:&#xD;
  15 without thrombotic event (neither at diagnosis nor during follow-up)&#xD;
  15 with thrombotic events (thrombosis at diagnosis or within 2 years of diagnosis)&#xD;
  15 who progressed to myelofibrosis or AML during follow-up</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Patients with PV</arm_group_label>
      <description>45 patients with PV&#xD;
  15 without thrombotic event (neither at diagnosis nor during follow-up)&#xD;
  15 with thrombotic event (thrombosis at diagnosis or within 2 years of diagnosis)&#xD;
  15 who progressed to myelofibrosis or AML during follow-up</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Patients with PMF</arm_group_label>
      <description>20 patients with PMF:&#xD;
  10 without transformation into AML&#xD;
  10 patients who progressed to AML</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Patients without MPN</arm_group_label>
      <description>10 patients without MPN</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Assessment of the epigenetic age</intervention_name>
      <description>Retrospective assessment of the epigenetic age on DNA samples obtained at diagnosis</description>
      <arm_group_label>Patients with ET</arm_group_label>
      <arm_group_label>Patients with PMF</arm_group_label>
      <arm_group_label>Patients with PV</arm_group_label>
      <arm_group_label>Patients without MPN</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Patients with Myeloproliferative Neoplasia (MPN) : Essential Thrombocythemia (ET),&#xD;
          Polycythemia Vera (VP) or Primary Myelofibrosis (PMF)&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          For the 110 patients with MPN:&#xD;
  &#xD;
            -  Patients with PV, ET or PMF&#xD;
  &#xD;
            -  DNA extracted from purified granulocytes at time of diagnosis&#xD;
  &#xD;
            -  No treatment likely to impact DNA methylation (chemotherapy, immunosuppressants in&#xD;
               particular)&#xD;
  &#xD;
          For the 10 subjects without MPN:&#xD;
  &#xD;
            -  Absence of hematological malignancy&#xD;
  &#xD;
            -  Search for JAK2V617F mutation in the context of reactive thrombocytosis or secondary&#xD;
               polycythemia&#xD;
  &#xD;
            -  Absence of treatment likely to impact DNA methylation (chemotherapy,&#xD;
               immunosuppressants in particular)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          For the 110 patients with MPN:&#xD;
  &#xD;
            -  Patients without PV, ET or PMF&#xD;
  &#xD;
            -  Patients without purified granulocytes DNA available at time of diagnosis&#xD;
  &#xD;
            -  Patients treated by cytoreductive drug, demethylating agent, chemotherapy or&#xD;
               immunosuppressive therapy at the time of DNA sampling&#xD;
  &#xD;
            -  Patients with less than 2 years' follow-up&#xD;
  &#xD;
          For the 10 subjects in NMP :&#xD;
  &#xD;
            -  Patients with hematological malignancy and/or solid cancer&#xD;
  &#xD;
            -  Patients treated by cytoreductive drug, demethylating agent, chemotherapy or&#xD;
               immunosuppressive therapy at the time of DNA sampling&#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>Olivier MANSIER</last_name>
      <email>olivier.mansier@chu-bordeaux.fr</email>
    </overall_contact>
    <location>
      <facility>
        <name>CHU de Bordeaux, service Hématologie Biologique</name>
        <address>
          <city>Bordeaux</city>
          <country>France</country>
        </address>
      </facility>
      <contact>
        <last_name>Olivier MANSIER</last_name>
        <email>olivier.mansier@chu-bordeaux.fr</email>
      </contact>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Myeloproliferative Neoplasm</keyword>
    <keyword>Epigenetic age</keyword>
    <keyword>Thrombosis</keyword>
    <keyword>Myelofibrosis</keyword>
    <keyword>Leukemia</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasms</mesh_term>
      <mesh_term>Myeloproliferative Disorders</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/NCT06022328
  org study id: CHUBX 2023/15
  nct id: NCT06022328
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Myeloproliferative Neoplasms (MPN) are hematological malignancies characterized by the
        excessive production of myeloid cells. MPN can be complicated by thrombosis and evolution
        into more aggressive diseases (myelofibrosis and acute leukemia). Aging remains the principal
        factor determining patients' survival in MPN. In recent years, DNA methylation has appeared
        as a mean to measure aging via the development of epigenetic clocks that have also been
        associated with the occurrence of thrombosis and cancer. The epiC project aims at determining
        epigenetic age of MPN patients and search for an association between this parameter and
        thrombotic/hematological complications.
  Myeloproliferative Neoplasia (MPN) are hematological malignancies characterized by the
        excessive production of myeloid cells. They include Essential Thrombocythemia (ET),
        Polycythemia Vera (VP) and Primary Myelofibrosis (PMF). Thrombosis are the most frequent
        complications and are largely responsible for the morbidity and mortality observed in ET and
        PV patients. The most feared complications are hematological transformations (into
        myelofibrosis for PV and ET, into acute myeloid leukemia for PV, ET and PMF). The prognostic
        assessment of MPN patients is mainly based on clinical data. Although recent studies have
        shown that certain mutations are associated with a poorer prognosis, age remains the main
        risk factor affecting survival in MPN patients. Recent studies have shown that DNA
        methylation can be used to determine an "epigenetic age". Interestingly, this epigenetic age
        is associated with the development of cardiovascular disease and cancer.
  
        In this project, the epigenetic age of MPN patients will be determined by studying the DNA
        methylation at diagnosis using the Infinium Human MethylationEPIC kit (Illumina). Epigenetic
        age will be determined with the most commonly used epigenetic clocks (DNAmAge, DNAmHannum,
        DNAmPhenoAge, DNAmSkinClock, DNAmGrimAge, intrinsic epigenetic age acceleration, extrinsic
        epigenetic age acceleration). It will be searched for an association between accelerated
        epigenetic aging (as assessed by the difference between epigenetic age and chronological age)
        and the type of MPN, the clinical and biological presentation at diagnosis (including the
        mutational profile of patients) and the occurrence of thrombosis and hematological evolution
        into myelofibrosis and/or acute leukemia.
  observational model: Cohort
  time perspective: Retrospective
  measure: Accelerated ageing of patients
  time frame: At inclusion, up to 1 year after diagnosis
  description: Accelerated ageing will be defined as an increased difference between the epigenetic age (calculated from DNA methylation data with the different molecular clocks described: DNAmAge, DNAmHannum, DNAmPhenoAge, DNAmSkinClock, DNAmGrimAge, intrinsic epigenetic age acceleration, extrinsic epigenetic age acceleration) and the chronological age
  measure: Type of MPN (ET, PV or PMF) at diagnosis
  time frame: At inclusion, up to 1 year after diagnosis
  description: We will study patients with a diagnosis of ET, PV or PMF as defined by the WHO classification of hematological malignancies
  measure: Transformation into secondary myelofibrosis or acute leukemia
  time frame: From date of inclusion until documentation of the event, assessed up to 5 years
  description: Evolution toward secondary myelofibrosis or acute leukemia will be defined according to the WHO classification of hematological malignancies
  measure: Occurrence of thrombosis prior to diagnosis or during follow-up of the disease
  time frame: Between 1 year before and 2 years after MPN diagnosis
  description: Occurrence of myocardial infarction, ischemic stroke, deep vein thrombosis, pulmonary embolism, splanchnic thrombosis or any other significant thrombosis. Tinnitus, vertigo, headaches, erythromelalgia as well as superficial vein thrombosis will not be considered as thrombotic events
  measure: Leukocytes
  time frame: At inclusion, up to 1 year after diagnosis
  description: Leukocytes level on blood count in G/L
  measure: Platelets
  time frame: At inclusion, up to 1 year after diagnosis
  description: Platelet level on blood count in G/L
  measure: Granulocytes
  time frame: At inclusion, up to 1 year after diagnosis
  description: Granulocytes level on blood count in G/L
  measure: Monocytes
  time frame: At inclusion, up to 1 year after diagnosis
  description: Monocytes level on blood count in G/L
  measure: Hemoglobin
  time frame: At inclusion, up to 1 year after diagnosis
  description: Hemoglobin level on blood count in g/dL
  measure: Hematocrit
  time frame: At inclusion, up to 1 year after diagnosis
  description: Hematocrit level on blood count in %
  measure: Additional somatic mutation
  time frame: At inclusion, up to 1 year after diagnosis
  description: In up to 50% of MPN patients, genetic variants can be detected in genes such as DNMT3A, TET2, ASXL1, SRSF2, SF3B1, U2AF1, EZH2 or TP53. We will determine which somatic genetic variant is detected by high throughput sequencing
  arm group label: Patients with ET
  description: 45 patients with ET:
  15 without thrombotic event (neither at diagnosis nor during follow-up)
  15 with thrombotic events (thrombosis at diagnosis or within 2 years of diagnosis)
  15 who progressed to myelofibrosis or AML during follow-up
  arm group label: Patients with PV
  description: 45 patients with PV
  15 without thrombotic event (neither at diagnosis nor during follow-up)
  15 with thrombotic event (thrombosis at diagnosis or within 2 years of diagnosis)
  15 who progressed to myelofibrosis or AML during follow-up
  arm group label: Patients with PMF
  description: 20 patients with PMF:
  10 without transformation into AML
  10 patients who progressed to AML
  arm group label: Patients without MPN
  description: 10 patients without MPN
  intervention type: Biological
  intervention name: Assessment of the epigenetic age
  description: Retrospective assessment of the epigenetic age on DNA samples obtained at diagnosis
  arm group label: Patients with ET
  arm group label: Patients with PMF
  arm group label: Patients with PV
  arm group label: Patients without MPN
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Olivier MANSIER
  email: olivier.mansier@chu-bordeaux.fr
  facility: 
  contact: 
  country: France
  responsible party type: Sponsor
  mesh term: Neoplasms
  mesh term: Myeloproliferative Disorders
  sharing ipd: No