<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/NCT03029728</url>
  </required_header>
  <id_info>
    <org_study_id>BHAE 06-2018</org_study_id>
    <nct_id>NCT03029728</nct_id>
  </id_info>
  <brief_title>Biomarker for Hereditary AngioEdema Disease</brief_title>
  <acronym>BioHAE</acronym>
  <official_title>Biomarker for Hereditary AngioEdema Disease: An International, Multicenter, Longitudinal Monitoring Protocol</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CENTOGENE GmbH Rostock</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </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>
      International, multicenter, observational, longitudinal monitoring study to identify,&#xD;
      validate and/or monitor Mass Spectrometry (MS)-based biomarker/s for Hereditary Angioedeme&#xD;
      (HAE) disease and to test the clinical robustness, specificity, and predictive value of&#xD;
      theese biomarker/s&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hereditary Angioedema (HAE) is a rare autosomal dominant genetic disorder, characterized by&#xD;
      recurrent episodes of angioedema of the face, larynx, lips, abdomen, and extremities.The most&#xD;
      common types of HAE develop as result of mutations in the SERPING1 gene that encodes the C1&#xD;
      inhibitor (C1-INH), a protease involved in limiting bradykinin production. Excessive&#xD;
      bradykinin due to low levels of C1-INH (HAE type 1) or dysfunctional C1-INH (HAE type 2)&#xD;
      leads to capillary leakage and angioedema formation. The third type of HAE is not associated&#xD;
      with a C1-INH deficiency, develops as a result of mutations in the Factor 12 gene (FXII) and&#xD;
      affects almost exclusively women. Rare cases of HAE have also been described resulting from&#xD;
      mutations in Plasminogen (PLG), Angiopoetin 1 (ANGPT1), and Kininogen 1 (KNG1).&#xD;
&#xD;
      The characteristic symptom of hereditary angioedema is recurrent episodes of swelling due to&#xD;
      the accumulation of excessive body fluid. The most commonly affected areas of the body&#xD;
      include the hands, feet, eyelids, lips, genitals, larynx and gastrointestinal tract. The most&#xD;
      serious complication of HAE is laryngeal edema that can become life threatening; but it is a&#xD;
      relatively rare event.&#xD;
&#xD;
      The diagnosis of hereditary angioedema is made by a thorough clinical evaluation, a detailed&#xD;
      patient history, and blood tests.Clinical diagnosis is complicated because HAE is highly&#xD;
      variable in the clinical phenotype and the majority of the physicians believe that they never&#xD;
      seen a patient with that disorder. Laboratory diagnosis involves measurement of the C1-INH&#xD;
      function, C1-INH and C4 levels. Both C1-INH protein level and function is low in HAE-1&#xD;
      patients, whereas in HAE-2 individuals the C1-INH concentrations is optimal or even elevated,&#xD;
      however C1-INH function is impaired. Generally, C4 levels are low in both HAE-1/2 patients.&#xD;
&#xD;
      CENTOGENE utilizes Liquid Chromatography-Multiple Reaction Monitoring Mass Spectrometry&#xD;
      (LC-MRM-MS) method to identify potential disease-specific biomarkers for HAE. Such&#xD;
      biomarker/s may support the early diagnosis and treatment monitoring and personalization in&#xD;
      the future.&#xD;
&#xD;
      Therefore, it is the goal of this study is to identify new biomarkers for HAE, validate the&#xD;
      identified biomarkers, and monitor these biomarkers longitudinally to determine their&#xD;
      clinical robustness, specificity, and predictive value.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 20, 2018</start_date>
  <completion_date type="Actual">March 11, 2022</completion_date>
  <primary_completion_date type="Actual">March 11, 2022</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>Identification, validation and/or monitoring of mass spectrometry (MS)-based biomarkers of Hereditary Angioedema (HAE) patients</measure>
    <time_frame>36 months</time_frame>
    <description>All samples will be analyzed for the identification of biomarker/s via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determination of the clinical robustness, specificity, and predictive value of the biomarker(s)</measure>
    <time_frame>36 months</time_frame>
    <description>Samples will be analyzed for the identified biomarker candidates via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">42</enrollment>
  <condition>C1 Esterase Inhibitor Deficiency</condition>
  <condition>Angio Edema</condition>
  <condition>C4 Deficiency</condition>
  <condition>HAE</condition>
  <condition>Hereditary Angioedema</condition>
  <condition>Hereditary Angioedema Type II</condition>
  <condition>Hereditary Angioedema Type III</condition>
  <condition>Hereditary Angioedema Type I</condition>
  <arm_group>
    <arm_group_label>Participants with Hereditary Angioedema</arm_group_label>
    <description>Participants diagnosed with Hereditary Angioedema disease aged between 2 months and 60 years</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 diagnosed with Hereditary Angioedema (HAE) disease&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        INCLUSION CRITERIA&#xD;
&#xD;
          -  Informed consent is obtained from the participant or participant's parent/legal&#xD;
             guardian&#xD;
&#xD;
          -  The participant is aged between 2 months and 60 years&#xD;
&#xD;
          -  The diagnosis of Hereditary Angioedema is confirmed by CENTOGENE&#xD;
&#xD;
        EXCLUSION CRITERIA&#xD;
&#xD;
          -  Inability to provide informed consent&#xD;
&#xD;
          -  Participant is younger than 2 months or older than 60 years&#xD;
&#xD;
          -  The diagnosis of Hereditary Angioedema disease is not confirmed by CENTOGENE&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Months</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter Bauer, MD</last_name>
    <role>Study Chair</role>
    <affiliation>CENTOGENE GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Arabkir JMC-ICAH</name>
      <address>
        <city>Yerevan</city>
        <zip>0014</zip>
        <country>Armenia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center of Allergy and Immunology</name>
      <address>
        <city>Tbilisi</city>
        <zip>0159</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Pediatric Genetics, Amrita Institute of Medical Sciences &amp; Research Centre</name>
      <address>
        <city>Kerola</city>
        <zip>682041</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica San Pablo de Surco</name>
      <address>
        <city>Lima</city>
        <zip>1030</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Uniwersytecki w Krakowie</name>
      <address>
        <city>Krakau</city>
        <zip>31-501</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrul Clinic Mediquest</name>
      <address>
        <city>Târgu-Mureş</city>
        <zip>547530</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sakarya University Research and Training Hospital</name>
      <address>
        <city>Sakarya</city>
        <zip>54100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Armenia</country>
    <country>Georgia</country>
    <country>India</country>
    <country>Peru</country>
    <country>Poland</country>
    <country>Romania</country>
    <country>Turkey</country>
  </location_countries>
  <removed_countries>
    <country>Egypt</country>
    <country>Germany</country>
  </removed_countries>
  <link>
    <url>http://centogene.com</url>
    <description>CENTOGENE is a rare disease company focused on transforming clinical, genetic, and biochemical data into medical solutions for patients</description>
  </link>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>January 18, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <last_update_submitted>March 23, 2022</last_update_submitted>
  <last_update_submitted_qc>March 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hereditary Angioedema</keyword>
  <keyword>Biomarker</keyword>
  <keyword>Hereditary Angioedema Type I</keyword>
  <keyword>Hereditary Angioedema Type II</keyword>
  <keyword>Hereditary Angioedema Type III</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Angioedema</mesh_term>
    <mesh_term>Angioedemas, Hereditary</mesh_term>
    <mesh_term>Hereditary Angioedema Types I and II</mesh_term>
    <mesh_term>Hereditary Angioedema Type III</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03029728
org study id: BHAE 06-2018
nct id: NCT03029728
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
International, multicenter, observational, longitudinal monitoring study to identify,
      validate and/or monitor Mass Spectrometry (MS)-based biomarker/s for Hereditary Angioedeme
      (HAE) disease and to test the clinical robustness, specificity, and predictive value of
      theese biomarker/s
Hereditary Angioedema (HAE) is a rare autosomal dominant genetic disorder, characterized by
      recurrent episodes of angioedema of the face, larynx, lips, abdomen, and extremities.The most
      common types of HAE develop as result of mutations in the SERPING1 gene that encodes the C1
      inhibitor (C1-INH), a protease involved in limiting bradykinin production. Excessive
      bradykinin due to low levels of C1-INH (HAE type 1) or dysfunctional C1-INH (HAE type 2)
      leads to capillary leakage and angioedema formation. The third type of HAE is not associated
      with a C1-INH deficiency, develops as a result of mutations in the Factor 12 gene (FXII) and
      affects almost exclusively women. Rare cases of HAE have also been described resulting from
      mutations in Plasminogen (PLG), Angiopoetin 1 (ANGPT1), and Kininogen 1 (KNG1).

      The characteristic symptom of hereditary angioedema is recurrent episodes of swelling due to
      the accumulation of excessive body fluid. The most commonly affected areas of the body
      include the hands, feet, eyelids, lips, genitals, larynx and gastrointestinal tract. The most
      serious complication of HAE is laryngeal edema that can become life threatening; but it is a
      relatively rare event.

      The diagnosis of hereditary angioedema is made by a thorough clinical evaluation, a detailed
      patient history, and blood tests.Clinical diagnosis is complicated because HAE is highly
      variable in the clinical phenotype and the majority of the physicians believe that they never
      seen a patient with that disorder. Laboratory diagnosis involves measurement of the C1-INH
      function, C1-INH and C4 levels. Both C1-INH protein level and function is low in HAE-1
      patients, whereas in HAE-2 individuals the C1-INH concentrations is optimal or even elevated,
      however C1-INH function is impaired. Generally, C4 levels are low in both HAE-1/2 patients.

      CENTOGENE utilizes Liquid Chromatography-Multiple Reaction Monitoring Mass Spectrometry
      (LC-MRM-MS) method to identify potential disease-specific biomarkers for HAE. Such
      biomarker/s may support the early diagnosis and treatment monitoring and personalization in
      the future.

      Therefore, it is the goal of this study is to identify new biomarkers for HAE, validate the
      identified biomarkers, and monitor these biomarkers longitudinally to determine their
      clinical robustness, specificity, and predictive value.
observational model: Cohort
time perspective: Prospective
measure: Identification, validation and/or monitoring of mass spectrometry (MS)-based biomarkers of Hereditary Angioedema (HAE) patients
time frame: 36 months
description: All samples will be analyzed for the identification of biomarker/s via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.
measure: Determination of the clinical robustness, specificity, and predictive value of the biomarker(s)
time frame: 36 months
description: Samples will be analyzed for the identified biomarker candidates via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.
arm group label: Participants with Hereditary Angioedema
description: Participants diagnosed with Hereditary Angioedema disease aged between 2 months and 60 years
Blood sample applied on the Dry Blood Spot (DBS) Filtercard (Centocard®)
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 2 Months
maximum age: 60 Years
healthy volunteers: No
last name: Peter Bauer, MD
role: Study Chair
affiliation: CENTOGENE GmbH
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Armenia
country: Georgia
country: India
country: Peru
country: Poland
country: Romania
country: Turkey
country: Egypt
country: Germany
url: http://centogene.com
description: CENTOGENE is a rare disease company focused on transforming clinical, genetic, and biochemical data into medical solutions for patients
responsible party type: Sponsor
mesh term: Angioedema
mesh term: Angioedemas, Hereditary
mesh term: Hereditary Angioedema Types I and II
mesh term: Hereditary Angioedema Type III
sharing ipd: Undecided