<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/NCT03237494</url>
  </required_header>
  <id_info>
    <org_study_id>TRAM2 analysis</org_study_id>
    <nct_id>NCT03237494</nct_id>
  </id_info>
  <brief_title>TRAMmoniTTR Study Genetic Screening of an At-risk Population for hATTR and Monitoring of TTR Positive Subjects</brief_title>
  <acronym>TRAMmoniTTR</acronym>
  <official_title>Genetic Screening of an At-risk Population for Hereditary TransthyRetin-related AMyloidosis and Longitudinal Monitoring of TTR Positive Subjects- A Multicenter Epidemiological Longitudinal Protocol</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CENTOGENE GmbH Rostock</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Alnylam Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>CENTOGENE GmbH Rostock</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>
      National, multicenter, epidemiological, longitudinal protocol to investigate the hATTR&#xD;
      prevalence in an at-risk population for Hereditary Transthyretin Amyloidosis (hATTR) and&#xD;
      subjects diagnosed with hATTR, to monitor the clinical status in TTR positive subjects and to&#xD;
      establish hATTR biomarker/s&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hereditary TransThyRetin Amyloidosis (hATTR) is a slowly progressive condition, that is&#xD;
      transmitted as an autosomal dominant trait and is characterized by abnormal extracellular&#xD;
      deposits of fibrillar, misfolded proteins (amyloid fibrils) in the body. Amyloid fibrils can&#xD;
      be deposited in different body compartments, such as the nerves, heart, gastrointestinal&#xD;
      tract, kidneys and brain, causing severe structural changes. More than 30 proteins can&#xD;
      trigger the formation of amyloid fibrils, 5 of which can infiltrate the heart and cause&#xD;
      cardiac amyloidosis.&#xD;
&#xD;
      One of these amyloidogenic protein is transthyretin, formerly known as prealbumin.&#xD;
      Transthyretin (TTR) is found primarily in the serum (secreted by the liver) and cerebrospinal&#xD;
      fluid (secreted by the choroid plexus) and functions as a carrier for the hormone thyroxine&#xD;
      (T4) and retinol-binding protein (bound to retinol or vitamin A). The destabilization of the&#xD;
      TTR protein and the formation of misfolded TTR.&#xD;
&#xD;
      It is the goal of this study to investigate the prevalence of Hereditary&#xD;
      Transthyretin-related Amyloidosis (hATTR) in a cohort of 5.000 subjects are at risk for&#xD;
      Hereditary Transthyretin Amyloidosis (hATTR) and subjects diagnosed with hATTR, to monitor&#xD;
      the clinical status in TTR positive subjects and to establish hATTR biomarker/s.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 20, 2017</start_date>
  <completion_date type="Anticipated">April 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2025</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>Analysis of prevalance of hATTR mutations among a cohort of participants at risk for hATTR.</measure>
    <time_frame>4 years</time_frame>
    <description>DBS-based genetic analyses of TTR gene will be perfomed via the combination of the Next-Generation Sequencing (the mutation will be confirmed by Sanger sequencing) and the Multiplex ligation-dependent probe amplification.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To monitor clinical status in TTR positive subjects.</measure>
    <time_frame>4 years</time_frame>
    <description>8 Follow up visits within 24 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Establishment of biomarker/s in TTR positive cohort.</measure>
    <time_frame>4 years</time_frame>
    <description>hATTR-positive samples will be analyzed for the identification of potential biomarkers (based on MS/MS-Tandem spectroscopy) and compared with the merged control samples in order establish a HAE specific biomarker.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">5000</enrollment>
  <condition>Transthyretin Amyloidosis</condition>
  <condition>Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy</condition>
  <condition>Transthyretin-Related (ATTR) Familial Amyloid Cardiomyopathy</condition>
  <condition>Polyneuropathies</condition>
  <condition>Cardiomyopathies</condition>
  <arm_group>
    <arm_group_label>Participants at risk for hATTR and participants diagnosed with hATTR</arm_group_label>
    <description>Participants 18 years of age or older</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood sample applied on the Dry Blood Spot (DBS) Filtercard (Centocard®)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Participants at risk for Hereditary Transthyretin Amyloidosis (hATTR) and participants&#xD;
        diagnosed with hATTR&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed consent is obtained from the participant&#xD;
&#xD;
          -  The participant is 18 years of age or older&#xD;
&#xD;
          -  The participant has no diagnosis of alcoholism according to international guidelines&#xD;
&#xD;
          -  The participant has not undergone chemotherapy for any carcinoma&#xD;
&#xD;
        AND&#xD;
&#xD;
        The participant is at risk for hATTR due to two or more the factors listed below:&#xD;
&#xD;
          -  cardiomyopathy or polyneuropathy with no obvious etiology atypical Chronic&#xD;
             Inflammatory Demyelinating Polyneuropathy (CIDP) or Motor Neuron Disease (MND)&#xD;
&#xD;
          -  autonomic dysfunction&#xD;
&#xD;
          -  hypertrophic cardiomyopathy or heart failure with preserved ejection fraction Left&#xD;
             Ventricular Hypertrophy (LVH)&#xD;
&#xD;
          -  bilateral carpal tunnel syndrome&#xD;
&#xD;
          -  spinal stenosis or spinal radiculopathy&#xD;
&#xD;
          -  gait disorders&#xD;
&#xD;
          -  ocular changes involving vitreous opacities&#xD;
&#xD;
          -  unexplained weight loss &gt;5kg&#xD;
&#xD;
          -  renal abnormalities&#xD;
&#xD;
          -  family history of hATTR&#xD;
&#xD;
          -  based on imaging or biopsy suspected for the wild type TTR (ATTR) and not genetically&#xD;
             tested for hATTR&#xD;
&#xD;
        OR • The participant is diagnosed with hATTR&#xD;
&#xD;
        OR&#xD;
&#xD;
        • The participant is a 1st or 2nd degree relative of the TTR positive subject&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Informed consent is not obtained from the participant&#xD;
&#xD;
          -  The participant is younger than 18 years of age&#xD;
&#xD;
          -  The participant has a diagnosis of alcoholism according to International guidelines&#xD;
&#xD;
          -  The participant has undergone chemotherapy for any carcinoma&#xD;
&#xD;
          -  The participant is not at risk for hATTR&#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>Peter Bauer, Prof.</last_name>
    <role>Study Chair</role>
    <affiliation>Centogene GmbH</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sabine Roesner</last_name>
    <phone>+49 381 80113657</phone>
    <email>sabine.roesner@centogene.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Kepler Universitätsklinikum, Klinik für Interne 1 - Kardiologie und internistische Intensivmedizin; Cardiology</name>
      <address>
        <city>Linz</city>
        <zip>4021</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Kepler Universitätsklinikum, Neuromed Campus; Neurology</name>
      <address>
        <city>Linz</city>
        <zip>4021</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Aachen, Neurology</name>
      <address>
        <city>Aachen</city>
        <zip>52074</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrea Maier, MD</last_name>
      <phone>+49 (0)2418088600</phone>
      <email>amaier@ukaachen.de</email>
    </contact>
    <investigator>
      <last_name>Maike Franziska Dohrn, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Andrea Maier, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Klinikum Westmünsterland GmbH, I. Medizinische Klinik und Interventionelle Kardiologie</name>
      <address>
        <city>Ahaus</city>
        <zip>48683</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alessandro Cuneo, MD</last_name>
      <phone>+49 (0)25619923471</phone>
      <email>a.cuneo@kmh-stadtlohn.de</email>
    </contact>
    <investigator>
      <last_name>Alessandro Cuneo, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Kreiskrankenhaus Altenburg, Neurology</name>
      <address>
        <city>Altenburg</city>
        <zip>04600</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jörg Berrouschot, MD</last_name>
      <phone>+49 (0)3447521380</phone>
      <email>neurologie@klinikum-altenburgerland.de</email>
    </contact>
    <investigator>
      <last_name>Jörg Berrouschot, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sächsisches Krankenhaus Arnsdorf, Akademisches Lehrkrankenhaus der TU Dresden, Neurology</name>
      <address>
        <city>Arnsdorf</city>
        <zip>01477</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Gemeinschaftspraxis Neurologie &amp; Psychiatrie im Stadtpalais</name>
      <address>
        <city>Aschaffenburg</city>
        <zip>63739</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jochen C. Ulzheimer, MD</last_name>
      <phone>+49 (0)6021449860</phone>
      <email>j-c-u@gmx.de</email>
    </contact>
    <investigator>
      <last_name>Jochen C. Ulzheimer, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Kerckhoff-Klinik GmbH, Klinik für Kardiologie, Cardiology</name>
      <address>
        <city>Bad Nauheim</city>
        <zip>61231</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andreas Rieth, MD</last_name>
      <phone>+49 (0)60329962000</phone>
      <email>a.rieth@kerckhoff-klinik.de</email>
    </contact>
    <investigator>
      <last_name>Andreas Rieth, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>RHÖN-KLINIKUM Campus Bad Neustadt, Neurology</name>
      <address>
        <city>Bad Neustadt An Der Saale</city>
        <zip>97616</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hassan Soda, MD</last_name>
      <phone>+49 (0)97716622356</phone>
      <email>hassan.soda@campus-nes.de</email>
    </contact>
    <investigator>
      <last_name>Hassan Soda, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Charité - Universitätsmedizin Berlin Funktionsdiagnostik und Stationen, Cardiology</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Florian Knebel, MD</last_name>
      <phone>+49 (0)30450513216</phone>
      <email>Fabian.Knebel@charite.de</email>
    </contact>
    <investigator>
      <last_name>Florian Knebel, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Charité Universitätsmedizin Berlin, Klinik für Neurologie, Neurology</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Katrin Hahn, MD</last_name>
      <phone>+49 (0)30450660049</phone>
      <email>Katrin.Hahn@charite.de</email>
    </contact>
    <investigator>
      <last_name>Katrin Hahn, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Charité Universitätsmedizin Berlin - Campus Virchow Klinikum (CVK), Cardiology</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carsten Tschöpe, MD</last_name>
      <phone>+49 (0)30450565499</phone>
      <email>Carsten.Tschoepe@charite.de</email>
    </contact>
    <investigator>
      <last_name>Carsten Tschöpe, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Klinikum Bielefeld, Klinik für Kardiologie und internistische Intensivmedizin, Cardiology</name>
      <address>
        <city>Bielefeld</city>
        <zip>33604</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christoph Stellbrink, MD</last_name>
      <phone>+49 (0)5215813481</phone>
      <email>christoph.stellbrink@klinikumbielefeld.de</email>
    </contact>
    <investigator>
      <last_name>Christoph Stellbrink, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Evangelisches Klinikum Bethel gGmbH v. Bodelschwinghsche Stiftungen Bethel, Neurology</name>
      <address>
        <city>Bielefeld</city>
        <zip>33617</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wolf-Rüdiger Schäbitz, MD</last_name>
      <phone>+49 (0)52177278301</phone>
      <email>Wolf.Schaebitz@evkb.de</email>
    </contact>
    <investigator>
      <last_name>Wolf-Rüdiger Schäbitz, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Klinikum Bremen Mitte gGmbH, Neurologische Klinik, Neurology</name>
      <address>
        <city>Bremen</city>
        <zip>28177</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Gesundheit Nord gGmbH - Klinikverband Bremen</name>
      <address>
        <city>Bremen</city>
        <zip>28211</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas Duning, Prof.</last_name>
    </contact>
    <contact_backup>
      <phone>0421-408-1286</phone>
      <email>Thomas.duning@gesundheitnord.de</email>
    </contact_backup>
    <investigator>
      <last_name>Thomas Duning, Prof.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Krankenhaus Buchholz und Winsen, gemeinnützige GmbH, Cardiology</name>
      <address>
        <city>Buchholz In Der Nordheide</city>
        <zip>21244</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Klaus Hertting, MD</last_name>
      <phone>+49 (0)4181131340</phone>
      <email>klaus.hertting@krankenhaus-buchholz.de</email>
    </contact>
    <investigator>
      <last_name>Klaus Hertting, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Krankenhaus Buchholz und Winsen, gemeinnützige GmbH, Neurology</name>
      <address>
        <city>Buchholz In Der Nordheide</city>
        <zip>21244</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Allgemeines Krankenhaus Celle, Neurology</name>
      <address>
        <city>Celle</city>
        <zip>29223</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Philipp Ettelt, MD</last_name>
      <phone>+49 (0)5141721400</phone>
      <email>Philipp.Ettelt@akh-celle.de</email>
    </contact>
    <investigator>
      <last_name>Ettelt Philipp, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>St. Vincenz Krankenhaus Datteln, Medizinische Klinik II, Cardiology</name>
      <address>
        <city>Datteln</city>
        <zip>45711</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marcus Bauer, MD</last_name>
      <phone>+49 (0)23631083140</phone>
      <email>m.bauer@vincenz-datteln.de</email>
    </contact>
    <investigator>
      <last_name>Marcus Bauer, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Klinikum Dortmund gGmbH,Stroke-Unit und Neurologische Intensivstation, Neurology</name>
      <address>
        <city>Dortmund</city>
        <zip>44137</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gernot Reimann, MD</last_name>
      <phone>+49 (0)23195321822</phone>
      <email>gernot.reimann@klinikumdo.de</email>
    </contact>
    <investigator>
      <last_name>Gernot Reimann, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>LVR Klinikum Düsseldorf, Neurology</name>
      <address>
        <city>Düsseldorf</city>
        <zip>40629</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rüdiger Seitz, MD</last_name>
      <phone>+49 (0)2119224601</phone>
      <email>ruediger.seitz@lvr.de</email>
    </contact>
    <investigator>
      <last_name>Rüdiger Seitz, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Martin Gropius Krankenhaus, Klinik für Neurologie, Neurology</name>
      <address>
        <city>Eberswalde</city>
        <zip>16225</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Erlangen, Cardiology</name>
      <address>
        <city>Erlangen</city>
        <zip>91045</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Steffan Achenbach, MD</last_name>
      <phone>+49 (0)91318535301</phone>
      <email>stephan.achenbach@uk-erlangen.de</email>
    </contact>
    <investigator>
      <last_name>Steffan Achenbach, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Alfried Krupp Krankenhaus Rüttenscheid, Neurology</name>
      <address>
        <city>Essen</city>
        <zip>45131</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Contilia Herz- und Gefäßzentrum, Elisabeth-Krankenhaus Essen, Cardiology</name>
      <address>
        <city>Essen</city>
        <zip>45138</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Robert Schueler, MD</last_name>
      <phone>+49 (0)2018973200</phone>
      <email>R.Schueler@contilia.de</email>
    </contact>
    <investigator>
      <last_name>Robert Schueler, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Kliniken an der Paar Friedberg Krankenhaus, Cardiology</name>
      <address>
        <city>Friedberg</city>
        <zip>86316</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Herz-Thorax-Zentrum Fulda, Klinikum Fulda gAG, Universitätsmedizin Marburg - Campus Fulda, Cardiology</name>
      <address>
        <city>Fulda</city>
        <zip>36043</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Volker Schächinger, MD</last_name>
      <phone>+49 (0)661845381</phone>
      <email>volker.schaechinger@klinikum-fulda.de</email>
    </contact>
    <investigator>
      <last_name>Volker Schächinger, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Giessen-Marburg, Neurology</name>
      <address>
        <city>Giessen</city>
        <zip>D-35385</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Manfred Kaps, MD</last_name>
      <phone>+49 (0)64198545301</phone>
      <email>Manfred.Kaps@neuro.med.uni-giessen.de</email>
    </contact>
    <investigator>
      <last_name>Manfred Kaps, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Greifswald der Ernst-Moritz-Arndt-Universität, Neurology</name>
      <address>
        <city>Greifswald</city>
        <zip>17489</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Universitätsmedizin Göttingen - Herzzentrum; Cardiology</name>
      <address>
        <city>Göttingen</city>
        <zip>37075</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Frauke Czepluch, MD</last_name>
      <phone>+49 (0)551398900</phone>
      <email>f.czepluch@med.uni-goettingen.de</email>
    </contact>
    <investigator>
      <last_name>Frauke Czepluch, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>kbo-Isar-Amper-Klinikum München-Ost, Klinik für Neurologie, Neurology</name>
      <address>
        <city>Haar</city>
        <zip>85540</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Martin-Luther-Universität, Universitätsklinik und Poliklinik für Neurologie, Neurology</name>
      <address>
        <city>Halle (Saale)</city>
        <zip>06120</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bernhard Sehm, MD</last_name>
      <phone>+49 (0)3455572205</phone>
      <email>bernhard.sehm@uk-halle.de</email>
    </contact>
    <investigator>
      <last_name>Bernhard Sehm, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Universitätsklinik und Poliklinik für Innere Medizin III, Cardiology</name>
      <address>
        <city>Halle (Saale)</city>
        <zip>06120</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alexander Vogt, MD</last_name>
      <phone>+49 (0)3453455572601</phone>
      <email>alexander.vogt@uk-halle.de</email>
    </contact>
    <investigator>
      <last_name>Alexander Vogt, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Asklepios Klinik St. Georg, Klinik für Neurologie</name>
      <address>
        <city>Hamburg</city>
        <zip>20099</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Universitäres Herzzentrum Hamburg, Klinik für Allgemeine und Interventionelle Kardiologie, Universitätsklinikum Hamburg-Eppendorf, Cardiology</name>
      <address>
        <city>Hamburg</city>
        <zip>20246</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Monica Patten-Hamel, MD</last_name>
      <phone>+49 (0)40741057975</phone>
      <email>patten@uke.de</email>
    </contact>
    <investigator>
      <last_name>Monica Patten-Hamel, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Neurologie Neuer Wall, Fachärzte für Neurologie &amp; Psychiatrie, Neurology</name>
      <address>
        <city>Hamburg</city>
        <zip>20354</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Albertinen-Krankenhaus, Cardiology</name>
      <address>
        <city>Hamburg</city>
        <zip>22457</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eva Cramer-Frommann, MD</last_name>
      <phone>+49 (0)4055886722</phone>
      <email>eva.cramer@albertinen.de</email>
    </contact>
    <investigator>
      <last_name>Herbert Naegele, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Asklepios Klinik Altona, Neurologische Abteilung mit überregionaler Stroke Unit, Neurophysiologie und Neurologischer Intensivmedizin</name>
      <address>
        <city>Hamburg</city>
        <zip>22763</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Medizinische Hochschule Hannover, Klinik für Neurologie; Neurology</name>
      <address>
        <city>Hannover</city>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas Skripuletz, MD</last_name>
      <phone>+49 (0)5115323816</phone>
      <email>skripuletz.thomas@mh-hannover.de</email>
    </contact>
    <investigator>
      <last_name>Thomas Skripuletz, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Heidelberg, Klinik für Kardiologie, Angiologie und Pneumologie, Cardiology</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fabian aus dem Siepen, MD</last_name>
      <phone>+49 (0)62215637678</phone>
      <email>Fabian.ausdemSiepen@med.uni-heidelberg.de</email>
    </contact>
    <investigator>
      <last_name>Fabian aus dem Siepen, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Lausitzer Seenland Klinikum GmbH, Klinik für Neurologie, Neurology</name>
      <address>
        <city>Hoyerswerda</city>
        <zip>02977</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Jena, Neurology</name>
      <address>
        <city>Jena</city>
        <zip>07740</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Otto W. Witte, MD</last_name>
      <phone>+49 (0)36419323401</phone>
      <email>Otto.Witte@med.uni-jena.de</email>
    </contact>
    <investigator>
      <last_name>Otto W. Witte, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>DRK-Kliniken Nordhessen gGmbH , Klinik für Neurologie und Klinische Neurophysiologie, Neurology</name>
      <address>
        <city>Kassel</city>
        <zip>34121</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Alexianer Krefeld GmbH, Krankenhaus Maria Hilf, Neurology</name>
      <address>
        <city>Krefeld</city>
        <zip>47805</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Leipzig, Neurology</name>
      <address>
        <city>Leipzig</city>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Petra Baum, MD</last_name>
      <phone>+49 (0)3419724248</phone>
      <email>petra.baum@medizin.uni-leipzig.de</email>
    </contact>
    <investigator>
      <last_name>Petra Baum, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Klinikum St. Georg gGmbH</name>
      <address>
        <city>Leipzig</city>
        <zip>04129</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ilka Schneider, Dr. med.</last_name>
      <phone>03419094268</phone>
      <email>ilka.schneider@sanktgeorg.de</email>
    </contact>
    <investigator>
      <last_name>Ilka Schneider, Dr. med.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Asklepios Fachklinikum Lübben, Neurology</name>
      <address>
        <city>Lübben</city>
        <zip>15907</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Universitäres Herzzentrum Lübeck, Medizinische Klinik II</name>
      <address>
        <city>Lübeck</city>
        <zip>23538</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tobias Graf, MD</last_name>
      <phone>+49 (0)45150044520</phone>
      <email>Tobias.Graf@uksh.de</email>
    </contact>
    <investigator>
      <last_name>Tobias Graf, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sana Kliniken Lübeck GmbH, Medizinische Klinik II</name>
      <address>
        <city>Lübeck</city>
        <zip>23560</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joachim Weil, MD</last_name>
      <phone>+49 (0)4515851681</phone>
      <email>Joachim.Weil@Sana.de</email>
    </contact>
    <investigator>
      <last_name>Joachim Weil, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>DRK Schmerz-Zentrum, Neurology</name>
      <address>
        <city>Mainz</city>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Neurologie; Neurology</name>
      <address>
        <city>Mainz</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Frank Birklein, MD</last_name>
      <phone>+49 (0)6131175486</phone>
      <email>frank.birklein@unimedizin-mainz.de</email>
    </contact>
    <investigator>
      <last_name>Frank Birklein, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Diakonissen Speyer-Mannheim, Diakonissenkrankenhaus Mannheim, Neurology</name>
      <address>
        <city>Mannheim</city>
        <zip>68163</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Neckar-Odenwald Kliniken gGmbH, Kreiskrankenhaus Mosbach, Kardiologie der Klinik für Innere Medizin</name>
      <address>
        <city>Mosbach</city>
        <zip>74821</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peter Oberst, MD</last_name>
      <phone>+49 (0)6261838430</phone>
      <email>Peter.Oberst@Neckar-Odenwald-Kliniken.de</email>
    </contact>
    <investigator>
      <last_name>Peter Oberst, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ökumenisches Hainich Klinikum gGmbH, Neurology</name>
      <address>
        <city>Mühlhausen</city>
        <zip>99974</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Friedrich-Baur-Institut, Neurologische Klinik und Poliklinik, Neurology</name>
      <address>
        <city>München</city>
        <zip>80336</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Beate Schlotter-Weigel, MD</last_name>
      <phone>+49 (0)89440057400</phone>
      <email>Beate.Schlotter-Weigel@med.uni-muenchen.de</email>
    </contact>
    <investigator>
      <last_name>Beate Schlotter-Weigel, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Kardiologie München Nord, Cardiology</name>
      <address>
        <city>München</city>
        <zip>80939</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hans Ullrich Ebersberger, MD</last_name>
      <phone>+49 (0)8985633450</phone>
      <email>info@kardiologie-mn.de</email>
    </contact>
    <investigator>
      <last_name>Hans Ullrich Ebersberger, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ludwig-Maximilians-Universität München, Klinikum Großhadern, Neurologische Klinik und Poliklinik &amp; Deutsches Schwindel- und Gleichgewichtszentrum DSGZ, Neurology</name>
      <address>
        <city>München</city>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Florian Schöberl, MD</last_name>
      <phone>+49 (0)89440076674</phone>
      <email>Florian.Schoeberl@med.uni-muenchen.de</email>
    </contact>
    <investigator>
      <last_name>Florian Schöberl, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Klinik und Poliklinik für Neurologie, Klinikum rechts der Isar, Technische Universität München</name>
      <address>
        <city>München</city>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Achim Berthele, MD</last_name>
      <phone>+49 (0)894140</phone>
      <phone_ext>4673</phone_ext>
      <email>achim.berthele@tum.de</email>
    </contact>
    <contact_backup>
      <last_name>Marcus Deschauer, MD</last_name>
      <phone>+49 (0)894140</phone>
      <phone_ext>4606</phone_ext>
      <email>marcus.deschauer@mri.tum.de</email>
    </contact_backup>
    <investigator>
      <last_name>Achim Berthele, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Praxis für Neurologie, Neurology</name>
      <address>
        <city>München</city>
        <zip>81825</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Ruppiner Kliniken GmbH,Hochschulklinikum der MHB, Neurology</name>
      <address>
        <city>Neuruppin</city>
        <zip>16816</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Kreiskrankenhaus Prignitz gGmbH, Neurology</name>
      <address>
        <city>Perleberg</city>
        <zip>19348</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marko Petrick, MD</last_name>
      <phone>+49 (0)3876303160</phone>
      <email>m.petrick@krankenhaus-prignitz.de</email>
    </contact>
    <investigator>
      <last_name>Marko Petrick, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Krankenhaus Barmherzige Brüder Regensburg, Klinik für Neurologie, Neurology</name>
      <address>
        <city>Regensburg</city>
        <zip>93049</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lukas Kremmler, MD</last_name>
      <phone>+49 (0)94136992427</phone>
      <email>Lukas.Kremmler@barmherzige-regensburg.de</email>
    </contact>
    <investigator>
      <last_name>Lukas Kremmler, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Regensburg, Cardiology</name>
      <address>
        <city>Regensburg</city>
        <zip>93053</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bernhard Unsöld, MD</last_name>
      <phone>+49 (0)9419447201</phone>
      <email>bernhard.unsoeld@ukr.de</email>
    </contact>
    <investigator>
      <last_name>Bernhard Unsöld, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Nordwest-Krankenhaus Sanderbusch gGmbH, Neurologische Klinik, Neurology</name>
      <address>
        <city>Sande</city>
        <zip>26452</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Sächsisches Krankenhaus Altscherbitz, Neurology</name>
      <address>
        <city>Schkeuditz</city>
        <zip>04435</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anne-Dorte Sperfeld, MD</last_name>
      <phone>+49 (0)34204872300</phone>
      <email>Anne-Dorte.Sperfeld@skhal.sms.sachsen.de</email>
    </contact>
    <investigator>
      <last_name>Anne-Dorte Sperfeld, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Jung-Stilling Klinikum Siegen, Diakonie Westfalen Süd Neuro, Neurogeriatrie, Neurology</name>
      <address>
        <city>Siegen</city>
        <zip>57074</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christian Tanislav, MD</last_name>
      <phone>+49 (0)27133340392</phone>
      <email>christian.tanislav@diakonie-sw.de</email>
    </contact>
    <investigator>
      <last_name>Christian Tanislav, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Elbe Klinikum Stade</name>
      <address>
        <city>Stade</city>
        <zip>21682</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Holger Schmidt, MD</last_name>
      <phone>+49 (0)4141 970</phone>
      <email>holger.schmidt@elbekliniken.de</email>
    </contact>
    <investigator>
      <last_name>Holger Schmidt, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Asklepios Fachklinikum Teupitz, Neurology</name>
      <address>
        <city>Teupitz</city>
        <zip>15755</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Tübingen, Zentrum für Neurologie</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alexander Grimm, MD</last_name>
      <phone>+49 (0)70712982342</phone>
      <email>alexander.grimm@med.uni-tuebingen.de</email>
    </contact>
    <investigator>
      <last_name>Alexander Grimm, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>NeuroPoint, Neurology</name>
      <address>
        <city>Ulm</city>
        <zip>89073</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Herbert Schreiber, MD</last_name>
      <phone>+49 (0)73160280440</phone>
      <email>schreiber@neurologie-ulm.de</email>
    </contact>
    <investigator>
      <last_name>Herbert Schreiber, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Ulm, Neurology</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Albert Ludolph, MD</last_name>
      <phone>+49 (0)7311771201</phone>
      <email>albert.ludolph@rku.de</email>
    </contact>
    <investigator>
      <last_name>Albert Ludolph, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sophien-u.Hufeland-Klinikum, Klinik für Neurologie und Klinische Neurophysiologie, Neurology</name>
      <address>
        <city>Weimar</city>
        <zip>99425</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rolf Malessa, MD</last_name>
      <phone>+49 (0)3643571300</phone>
      <email>neurologie@klinikum-weimar.de</email>
    </contact>
    <investigator>
      <last_name>Rolf Malessa, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Fachkrankenhaus Hubertusburg gGmbH, Neurologische Klinik, Neurology</name>
      <address>
        <city>Wermsdorf</city>
        <zip>04779</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Adrian Trommer, MD</last_name>
      <phone>+49 (0)3436460</phone>
      <email>adrian.trommer@googlemail.com</email>
    </contact>
    <investigator>
      <last_name>Adrian Trommer, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sana HANSE Klinikum Wismar, Klinik für Neurologie, Neurology</name>
      <address>
        <city>Wismar</city>
        <zip>23966</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sabine Mehnert, MD</last_name>
      <phone>+49 (0)3841331262</phone>
      <email>sabine.mehnert@sana.de</email>
    </contact>
    <investigator>
      <last_name>Sabine Mehnert, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Praxis für Neurologie, Neurology</name>
      <address>
        <city>Wolfratshausen</city>
        <zip>v</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Luzerner Kantonspital, Cardiology</name>
      <address>
        <city>Luzern</city>
        <zip>6000</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Solothurner Spitäler AG, Bürgerspital Solothurn, Cardiology</name>
      <address>
        <city>Olten</city>
        <zip>4500</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Praxisgemeinschaft für Kardiologie, Innere Medizin und Psychosomatische Medizin, Cardiology</name>
      <address>
        <city>Zug</city>
        <zip>6300</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Germany</country>
    <country>Switzerland</country>
  </location_countries>
  <link>
    <url>http://www.centogene.com</url>
    <description>Centogene GmbH web page</description>
  </link>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>July 31, 2017</study_first_submitted>
  <study_first_submitted_qc>July 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 2, 2017</study_first_posted>
  <last_update_submitted>September 6, 2023</last_update_submitted>
  <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Peripheral Nervous System Diseases</keyword>
  <keyword>Transthyretin Amyloidosis</keyword>
  <keyword>Transthyretin-related familial amyloid polyneuropathy</keyword>
  <keyword>Transthyretin-related familial amyloid cardiomyopathy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polyneuropathies</mesh_term>
    <mesh_term>Amyloid Neuropathies, Familial</mesh_term>
    <mesh_term>Amyloid Neuropathies</mesh_term>
    <mesh_term>Cardiomyopathies</mesh_term>
    <mesh_term>Amyloidosis</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/NCT03237494
org study id: TRAM2 analysis
nct id: NCT03237494
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
National, multicenter, epidemiological, longitudinal protocol to investigate the hATTR
      prevalence in an at-risk population for Hereditary Transthyretin Amyloidosis (hATTR) and
      subjects diagnosed with hATTR, to monitor the clinical status in TTR positive subjects and to
      establish hATTR biomarker/s
Hereditary TransThyRetin Amyloidosis (hATTR) is a slowly progressive condition, that is
      transmitted as an autosomal dominant trait and is characterized by abnormal extracellular
      deposits of fibrillar, misfolded proteins (amyloid fibrils) in the body. Amyloid fibrils can
      be deposited in different body compartments, such as the nerves, heart, gastrointestinal
      tract, kidneys and brain, causing severe structural changes. More than 30 proteins can
      trigger the formation of amyloid fibrils, 5 of which can infiltrate the heart and cause
      cardiac amyloidosis.

      One of these amyloidogenic protein is transthyretin, formerly known as prealbumin.
      Transthyretin (TTR) is found primarily in the serum (secreted by the liver) and cerebrospinal
      fluid (secreted by the choroid plexus) and functions as a carrier for the hormone thyroxine
      (T4) and retinol-binding protein (bound to retinol or vitamin A). The destabilization of the
      TTR protein and the formation of misfolded TTR.

      It is the goal of this study to investigate the prevalence of Hereditary
      Transthyretin-related Amyloidosis (hATTR) in a cohort of 5.000 subjects are at risk for
      Hereditary Transthyretin Amyloidosis (hATTR) and subjects diagnosed with hATTR, to monitor
      the clinical status in TTR positive subjects and to establish hATTR biomarker/s.
observational model: Cohort
time perspective: Prospective
measure: Analysis of prevalance of hATTR mutations among a cohort of participants at risk for hATTR.
time frame: 4 years
description: DBS-based genetic analyses of TTR gene will be perfomed via the combination of the Next-Generation Sequencing (the mutation will be confirmed by Sanger sequencing) and the Multiplex ligation-dependent probe amplification.
measure: To monitor clinical status in TTR positive subjects.
time frame: 4 years
description: 8 Follow up visits within 24 months
measure: Establishment of biomarker/s in TTR positive cohort.
time frame: 4 years
description: hATTR-positive samples will be analyzed for the identification of potential biomarkers (based on MS/MS-Tandem spectroscopy) and compared with the merged control samples in order establish a HAE specific biomarker.
arm group label: Participants at risk for hATTR and participants diagnosed with hATTR
description: Participants 18 years of age or older
Blood sample applied on the Dry Blood Spot (DBS) Filtercard (Centocard®)
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Peter Bauer, Prof.
role: Study Chair
affiliation: Centogene GmbH
last name: Sabine Roesner
phone: +49 381 80113657
email: sabine.roesner@centogene.com
facility: 
status: Completed
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status: Completed
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status: Recruiting
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status: Completed
country: Austria
country: Germany
country: Switzerland
url: http://www.centogene.com
description: Centogene GmbH web page
responsible party type: Sponsor
mesh term: Polyneuropathies
mesh term: Amyloid Neuropathies, Familial
mesh term: Amyloid Neuropathies
mesh term: Cardiomyopathies
mesh term: Amyloidosis