<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/NCT03268161</url>
  </required_header>
  <id_info>
    <org_study_id>35RC15_3018</org_study_id>
    <nct_id>NCT03268161</nct_id>
  </id_info>
  <brief_title>Prevalence of Genetic Mutations in Patients With Neuropathy Associated With Anti-Myelin-associated Glycoprotein (MAG) Antibodies</brief_title>
  <acronym>GENOMAG</acronym>
  <official_title>Observational Study of the Prevalence of Some Genetic Mutations in Patients With Neuropathy Associated With Anti-Myelin-associated Glycoprotein (MAG) Antibodies.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rennes University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rennes University Hospital</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>
      Anti-MAG (Myelin Associated Glycoprotein) neuropathy is related to clonal B lymphocyte&#xD;
      proliferation producing an monoclonal immunoglobulin (IgM) with anti-MAG activity. IgM may be&#xD;
      a reflection of malignant lymphoproliferative syndrome (Waldenström disease) or, more often,&#xD;
      monoclonal gammopathy of unknown significance.&#xD;
&#xD;
      The anti-MAG antibody has a direct toxicity on the myelin sheath of the peripheral nervous&#xD;
      system responsible for a length-dependent demyelinating polyneuropathy. Clinically, this&#xD;
      results in a sensitive, ataxic predominant polyneuropathy in the lower limbs, sometimes&#xD;
      associated with a tremor of attitude and action tremor of the upper limbs.&#xD;
&#xD;
      Clonal B cells at the origin of IgM production may have acquired mutations affecting MYD88&#xD;
      (MYD88 L265P mutation) and CXCR4 (Whim-like CXCR4 mutation). The prevalence of the MYD88&#xD;
      L265P mutation is estimated to be 50% in monoclonal gammopathies of undetermined significance&#xD;
      and more than 80% in Waldenström disease. CXCR4 Whim-like mutations are found in 40% of&#xD;
      patients with Waldenström's disease.&#xD;
&#xD;
      No studies have reported the prevalence of these mutations in patients with anti-MAG&#xD;
      neuropathies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a retrospective observational study in patients with anti-MAG neuropathy. Mutational&#xD;
      analysis will be performed for patients with a medullary or blood sample stored in a bio-bank&#xD;
      during lymphocyte phenotyping. This phenotyping was carried out most often in search of a&#xD;
      malignant haemopathy associated with the monoclonal peak. No new samples were taken from the&#xD;
      patient (blood or spinal cord).&#xD;
&#xD;
      Immunoglobulin gene rearrangement of the clonal B cells are also assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 21, 2015</start_date>
  <completion_date type="Actual">November 10, 2017</completion_date>
  <primary_completion_date type="Actual">November 10, 2017</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>Prevalence of MYD88 L265P mutations in anti-MAG neuropathies</measure>
    <time_frame>At inclusion : after the patient's given consent</time_frame>
    <description>Mutational status of MYD88 L265P is assessed using high-throughput sequencing (HTS) and allele specific polymerase chain reaction (AS-PCR)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Prevalence of CXCR4 Whim-like mutations in anti-MAG neuropathies</measure>
    <time_frame>At inclusion : after the patient's given consent</time_frame>
    <description>Mutational status of CXCR4 is assessed using HTS and AS-PCR</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immunoglobulin gene rearrangement</measure>
    <time_frame>At inclusion : after the patient's given consent</time_frame>
    <description>Immunoglobulin gene rearrangements are determined with a multiplex PCR</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">26</enrollment>
  <condition>Neuropathy Demyelinating</condition>
  <arm_group>
    <arm_group_label>Patients with anti-MAG neuropathy</arm_group_label>
    <description>Mutational analysis of clonal B cells</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Mutational analysis of clonal B cells</intervention_name>
    <description>Mutational analysis based on medullary or blood samples stored in a bio-bank during routine lymphocyte phenotyping.&#xD;
Mutations affecting MYD88 (MYD88 L265P mutation), CXCR4 (Whim-like CXCR4 mutation) loci are sought.</description>
    <arm_group_label>Patients with anti-MAG neuropathy</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Medullary or blood sample stored in a bio-bank during lymphocyte phenotyping&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with anti-MAG neuropathy followed in the Internal Medicine Ward of the Rennes&#xD;
        University Hospital&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with anti-MAG neuropathy&#xD;
&#xD;
          -  Blood and/or bone marrow samples available in bio-bank&#xD;
&#xD;
          -  Given informed consent&#xD;
&#xD;
        Exclusion criterion&#xD;
&#xD;
          -  Participation refusal&#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_official>
    <last_name>Olivier DECAUX, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>CHU Rennes</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rennes University Hospital</name>
      <address>
        <city>Rennes</city>
        <zip>35000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>August 29, 2017</study_first_submitted>
  <study_first_submitted_qc>August 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <last_update_submitted>February 26, 2018</last_update_submitted>
  <last_update_submitted_qc>February 26, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 27, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>anti-MAG neuropathy</keyword>
  <keyword>Waldenström disease</keyword>
  <keyword>Mutational analysis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peripheral Nervous System Diseases</mesh_term>
  </condition_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/NCT03268161
org study id: 35RC15_3018
nct id: NCT03268161
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Anti-MAG (Myelin Associated Glycoprotein) neuropathy is related to clonal B lymphocyte
      proliferation producing an monoclonal immunoglobulin (IgM) with anti-MAG activity. IgM may be
      a reflection of malignant lymphoproliferative syndrome (Waldenström disease) or, more often,
      monoclonal gammopathy of unknown significance.

      The anti-MAG antibody has a direct toxicity on the myelin sheath of the peripheral nervous
      system responsible for a length-dependent demyelinating polyneuropathy. Clinically, this
      results in a sensitive, ataxic predominant polyneuropathy in the lower limbs, sometimes
      associated with a tremor of attitude and action tremor of the upper limbs.

      Clonal B cells at the origin of IgM production may have acquired mutations affecting MYD88
      (MYD88 L265P mutation) and CXCR4 (Whim-like CXCR4 mutation). The prevalence of the MYD88
      L265P mutation is estimated to be 50% in monoclonal gammopathies of undetermined significance
      and more than 80% in Waldenström disease. CXCR4 Whim-like mutations are found in 40% of
      patients with Waldenström's disease.

      No studies have reported the prevalence of these mutations in patients with anti-MAG
      neuropathies.
This is a retrospective observational study in patients with anti-MAG neuropathy. Mutational
      analysis will be performed for patients with a medullary or blood sample stored in a bio-bank
      during lymphocyte phenotyping. This phenotyping was carried out most often in search of a
      malignant haemopathy associated with the monoclonal peak. No new samples were taken from the
      patient (blood or spinal cord).

      Immunoglobulin gene rearrangement of the clonal B cells are also assessed.
observational model: Cohort
time perspective: Retrospective
measure: Prevalence of MYD88 L265P mutations in anti-MAG neuropathies
time frame: At inclusion : after the patient's given consent
description: Mutational status of MYD88 L265P is assessed using high-throughput sequencing (HTS) and allele specific polymerase chain reaction (AS-PCR)
measure: Prevalence of CXCR4 Whim-like mutations in anti-MAG neuropathies
time frame: At inclusion : after the patient's given consent
description: Mutational status of CXCR4 is assessed using HTS and AS-PCR
measure: Immunoglobulin gene rearrangement
time frame: At inclusion : after the patient's given consent
description: Immunoglobulin gene rearrangements are determined with a multiplex PCR
arm group label: Patients with anti-MAG neuropathy
description: Mutational analysis of clonal B cells
intervention type: Diagnostic Test
intervention name: Mutational analysis of clonal B cells
description: Mutational analysis based on medullary or blood samples stored in a bio-bank during routine lymphocyte phenotyping.
Mutations affecting MYD88 (MYD88 L265P mutation), CXCR4 (Whim-like CXCR4 mutation) loci are sought.
arm group label: Patients with anti-MAG neuropathy
Medullary or blood sample stored in a bio-bank during lymphocyte phenotyping
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Olivier DECAUX, MD, PhD
role: Study Director
affiliation: CHU Rennes
facility: 
country: France
responsible party type: Sponsor
mesh term: Peripheral Nervous System Diseases
sharing ipd: No