<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/NCT03809091</url>
  </required_header>
  <id_info>
    <org_study_id>WGS_UNK_BE</org_study_id>
    <nct_id>NCT03809091</nct_id>
  </id_info>
  <brief_title>WGS of Korean Idiopathic Bronchiectasis</brief_title>
  <acronym>WGS_UNK_BE</acronym>
  <official_title>Whole Genome Sequencing of Korean Patients With Idiopathic Bronchiectasis for Identification of Disease-Causing Variants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seoul National University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Seoul National 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>
      Whole genome sequencing of Korean patients with idiopathic bronchiectasis and their family&#xD;
      will perform to identify disease-causing variants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Idiopathic bronchiectasis may be a manifestation of genetic diseases such as cystic fibrosis,&#xD;
      primary ciliary dyskinesia, etc. Diagnosis of these rare genetic diseases is crucial not only&#xD;
      because some of the rare diseases developed already effective treatment options, but also the&#xD;
      detection of syndrome enables us to detect other organ damages before the deterioration of&#xD;
      them.&#xD;
&#xD;
      Several diagnostic tools have been developed; however, the genetic panel has limited&#xD;
      screening efficacy due to the genetic heterogeneity of diseases. Even more, especially in&#xD;
      Korea, the incidence of idiopathic bronchiectasis caused by the genetic disease is rare, most&#xD;
      clinics have limited to assess specialized diagnostic tools such as the specialized genetic&#xD;
      panels, sweat chloride test, and the electromagnetic detection tools for ciliary movement.&#xD;
&#xD;
      Whole genome sequencing may be an excellent solution to identify the neglected genetic&#xD;
      diseases causing idiopathic bronchiectasis and explore the heterogeneity of disease-causing&#xD;
      variants in Korean patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">January 2019</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">August 2021</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Family-Based</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>3 Years</target_duration>
  <primary_outcome>
    <measure>Number of diagnosed patients by using whole genome sequencing</measure>
    <time_frame>3 years</time_frame>
    <description>The primary objective of this study is to evaluate the effectiveness of whole-genome sequencing (WGS) for idiopathic bronchiectasis patients in Korea. The number of patients newly diagnosed with WGS who are previously not diagnosed will be the primary outcome.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Bronchiectasis Idiopathic</condition>
  <condition>Cystic Fibrosis</condition>
  <condition>Primary Ciliary Dyskinesia</condition>
  <arm_group>
    <arm_group_label>Bronchiectasis</arm_group_label>
    <description>The patient with bronchiectasis who has no apparent bronchiectasis-causing etiology will be enrolled. The patient's family who has no bronchiectasis will be also enrolled to identify the patient-specific variants.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Whole genome sequencing</intervention_name>
    <description>Whole genome sequencing of patients and their family will be performed. Among the variants detected by WGS, disease-causing variants will be analyzed by using segregation analysis.</description>
    <arm_group_label>Bronchiectasis</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      DNA will be extracted from whole blood samples of patients and their family.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Among the patients visiting Seoul National Univerisity Hospital outpatient clinic,&#xD;
        bronchiectasis patients who have no clear etiology of bronchiectasis and their family will&#xD;
        be enrolled.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  If the patient has bronchiectasis proved by computed tomography (CT).&#xD;
&#xD;
          -  The clinical features of the patient are suitable for ciliary dysfunction disease&#xD;
             (primary ciliary dyskinesia, cystic fibrosis), alpha1-antitrypsin deficiency, and&#xD;
             primary immune deficiency (hyper-immunoglobulin E syndrome, hypogammaglobulinemia,&#xD;
             activated phosphoinositide 3-kinase (PI3K) delta syndrome, bare lymphocyte syndrome)&#xD;
&#xD;
          -  The patient has no apparent medical events causing bronchiectasis.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  If the patient does not agree or withdraw&#xD;
&#xD;
          -  If the patient has any clear etiology causing bronchiectasis including AIDS,&#xD;
             malignancy, receiving immunosuppressant or chemotherapy.&#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>Jae-June Yim, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Division of Pulmonology and Critical Care Medicine, Seoul National University College of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jae-June Yim, MD</last_name>
    <phone>+82-2-2072-2059</phone>
    <email>yimjj@snu.ac.kr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine</name>
      <address>
        <city>Seoul</city>
        <zip>110-744</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jae-Joon Yim, MD</last_name>
      <phone>+82-2-2072-2059</phone>
      <email>yimjj@snu.ac.kr</email>
    </contact>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <link>
    <url>https://doi.org/10.1101/438838</url>
    <description>Whole genome sequencing enables definitive diagnosis of Cystic Fibrosis and Primary Ciliary Dyskinesia, bioRxiv, 2018</description>
  </link>
  <reference>
    <citation>Hill AT, Sullivan AL, Chalmers JD, De Soyza A, Elborn SJ, Floto AR, Grillo L, Gruffydd-Jones K, Harvey A, Haworth CS, Hiscocks E, Hurst JR, Johnson C, Kelleher PW, Bedi P, Payne K, Saleh H, Screaton NJ, Smith M, Tunney M, Whitters D, Wilson R, Loebinger MR. British Thoracic Society Guideline for bronchiectasis in adults. Thorax. 2019 Jan;74(Suppl 1):1-69. doi: 10.1136/thoraxjnl-2018-212463. No abstract available.</citation>
    <PMID>30545985</PMID>
  </reference>
  <reference>
    <citation>Lonni S, Chalmers JD, Goeminne PC, McDonnell MJ, Dimakou K, De Soyza A, Polverino E, Van de Kerkhove C, Rutherford R, Davison J, Rosales E, Pesci A, Restrepo MI, Torres A, Aliberti S. Etiology of Non-Cystic Fibrosis Bronchiectasis in Adults and Its Correlation to Disease Severity. Ann Am Thorac Soc. 2015 Dec;12(12):1764-70. doi: 10.1513/AnnalsATS.201507-472OC.</citation>
    <PMID>26431397</PMID>
  </reference>
  <reference>
    <citation>Chandrasekaran R, Mac Aogain M, Chalmers JD, Elborn SJ, Chotirmall SH. Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis. BMC Pulm Med. 2018 May 22;18(1):83. doi: 10.1186/s12890-018-0638-0.</citation>
    <PMID>29788932</PMID>
  </reference>
  <reference>
    <citation>Splinter K, Adams DR, Bacino CA, Bellen HJ, Bernstein JA, Cheatle-Jarvela AM, Eng CM, Esteves C, Gahl WA, Hamid R, Jacob HJ, Kikani B, Koeller DM, Kohane IS, Lee BH, Loscalzo J, Luo X, McCray AT, Metz TO, Mulvihill JJ, Nelson SF, Palmer CGS, Phillips JA 3rd, Pick L, Postlethwait JH, Reuter C, Shashi V, Sweetser DA, Tifft CJ, Walley NM, Wangler MF, Westerfield M, Wheeler MT, Wise AL, Worthey EA, Yamamoto S, Ashley EA; Undiagnosed Diseases Network. Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease. N Engl J Med. 2018 Nov 29;379(22):2131-2139. doi: 10.1056/NEJMoa1714458. Epub 2018 Oct 10.</citation>
    <PMID>30304647</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>January 23, 2019</last_update_submitted>
  <last_update_submitted_qc>January 23, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Seoul National University Hospital</investigator_affiliation>
    <investigator_full_name>Jae-Joon Yim</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Bronchiectasis</mesh_term>
    <mesh_term>Ciliary Motility Disorders</mesh_term>
    <mesh_term>Dyskinesias</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/NCT03809091
org study id: WGS_UNK_BE
nct id: NCT03809091
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Whole genome sequencing of Korean patients with idiopathic bronchiectasis and their family
      will perform to identify disease-causing variants.
Idiopathic bronchiectasis may be a manifestation of genetic diseases such as cystic fibrosis,
      primary ciliary dyskinesia, etc. Diagnosis of these rare genetic diseases is crucial not only
      because some of the rare diseases developed already effective treatment options, but also the
      detection of syndrome enables us to detect other organ damages before the deterioration of
      them.

      Several diagnostic tools have been developed; however, the genetic panel has limited
      screening efficacy due to the genetic heterogeneity of diseases. Even more, especially in
      Korea, the incidence of idiopathic bronchiectasis caused by the genetic disease is rare, most
      clinics have limited to assess specialized diagnostic tools such as the specialized genetic
      panels, sweat chloride test, and the electromagnetic detection tools for ciliary movement.

      Whole genome sequencing may be an excellent solution to identify the neglected genetic
      diseases causing idiopathic bronchiectasis and explore the heterogeneity of disease-causing
      variants in Korean patients.
observational model: Family-Based
time perspective: Prospective
measure: Number of diagnosed patients by using whole genome sequencing
time frame: 3 years
description: The primary objective of this study is to evaluate the effectiveness of whole-genome sequencing (WGS) for idiopathic bronchiectasis patients in Korea. The number of patients newly diagnosed with WGS who are previously not diagnosed will be the primary outcome.
arm group label: Bronchiectasis
description: The patient with bronchiectasis who has no apparent bronchiectasis-causing etiology will be enrolled. The patient's family who has no bronchiectasis will be also enrolled to identify the patient-specific variants.
intervention type: Diagnostic Test
intervention name: Whole genome sequencing
description: Whole genome sequencing of patients and their family will be performed. Among the variants detected by WGS, disease-causing variants will be analyzed by using segregation analysis.
arm group label: Bronchiectasis
DNA will be extracted from whole blood samples of patients and their family.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jae-June Yim, MD
role: Principal Investigator
affiliation: Division of Pulmonology and Critical Care Medicine, Seoul National University College of Medicine
last name: Jae-June Yim, MD
phone: +82-2-2072-2059
email: yimjj@snu.ac.kr
facility: 
status: Recruiting
contact: 
country: Korea, Republic of
url: https://doi.org/10.1101/438838
description: Whole genome sequencing enables definitive diagnosis of Cystic Fibrosis and Primary Ciliary Dyskinesia, bioRxiv, 2018
citation: Hill AT, Sullivan AL, Chalmers JD, De Soyza A, Elborn SJ, Floto AR, Grillo L, Gruffydd-Jones K, Harvey A, Haworth CS, Hiscocks E, Hurst JR, Johnson C, Kelleher PW, Bedi P, Payne K, Saleh H, Screaton NJ, Smith M, Tunney M, Whitters D, Wilson R, Loebinger MR. British Thoracic Society Guideline for bronchiectasis in adults. Thorax. 2019 Jan;74(Suppl 1):1-69. doi: 10.1136/thoraxjnl-2018-212463. No abstract available.
PMID: 30545985
citation: Lonni S, Chalmers JD, Goeminne PC, McDonnell MJ, Dimakou K, De Soyza A, Polverino E, Van de Kerkhove C, Rutherford R, Davison J, Rosales E, Pesci A, Restrepo MI, Torres A, Aliberti S. Etiology of Non-Cystic Fibrosis Bronchiectasis in Adults and Its Correlation to Disease Severity. Ann Am Thorac Soc. 2015 Dec;12(12):1764-70. doi: 10.1513/AnnalsATS.201507-472OC.
PMID: 26431397
citation: Chandrasekaran R, Mac Aogain M, Chalmers JD, Elborn SJ, Chotirmall SH. Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis. BMC Pulm Med. 2018 May 22;18(1):83. doi: 10.1186/s12890-018-0638-0.
PMID: 29788932
citation: Splinter K, Adams DR, Bacino CA, Bellen HJ, Bernstein JA, Cheatle-Jarvela AM, Eng CM, Esteves C, Gahl WA, Hamid R, Jacob HJ, Kikani B, Koeller DM, Kohane IS, Lee BH, Loscalzo J, Luo X, McCray AT, Metz TO, Mulvihill JJ, Nelson SF, Palmer CGS, Phillips JA 3rd, Pick L, Postlethwait JH, Reuter C, Shashi V, Sweetser DA, Tifft CJ, Walley NM, Wangler MF, Westerfield M, Wheeler MT, Wise AL, Worthey EA, Yamamoto S, Ashley EA; Undiagnosed Diseases Network. Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease. N Engl J Med. 2018 Nov 29;379(22):2131-2139. doi: 10.1056/NEJMoa1714458. Epub 2018 Oct 10.
PMID: 30304647
responsible party type: Principal Investigator
investigator affiliation: Seoul National University Hospital
investigator full name: Jae-Joon Yim
investigator title: Professor
mesh term: Cystic Fibrosis
mesh term: Bronchiectasis
mesh term: Ciliary Motility Disorders
mesh term: Dyskinesias
sharing ipd: No