<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/NCT03791086</url>
  </required_header>
  <id_info>
    <org_study_id>2017RC11</org_study_id>
    <nct_id>NCT03791086</nct_id>
  </id_info>
  <brief_title>The BRIDGE Study - Bronchiectasis Research Involving Databases, Genomics and Endotyping</brief_title>
  <acronym>BRIDGE</acronym>
  <official_title>The BRIDGE Study - Bronchiectasis Research Involving Databases, Genomics and Endotyping. An EMBARC2 and EMBARC3 Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Dundee</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Dundee</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>
      Bronchiectasis is a complex heterogeneous disorder. Treatment is challenging and many recent&#xD;
      randomized controlled trials have been negative. It is believed that bronchiectasis as a&#xD;
      broad diagnosis incorporates multiple different patient subgroups (also known as phenotypes)&#xD;
      and molecular entities (referred to as endotypes). This study aims to phenotype and endotype&#xD;
      bronchiectasis during stable disease and exacerbations, to develop strategies for&#xD;
      personalised medicine.&#xD;
&#xD;
      Primary Objective To determine molecular endotypes of bronchiectasis which can guide response&#xD;
      to treatment.&#xD;
&#xD;
      Secondary Objectives&#xD;
&#xD;
        1. To determine molecular endotypes of stable bronchiectasis&#xD;
&#xD;
        2. To determine the causes and inflammatory profiles of bronchiectasis exacerbations&#xD;
&#xD;
        3. To validate candidate biomarkers of stable and exacerbation endotypes to use in&#xD;
           stratified medicine&#xD;
&#xD;
        4. To perform in-vivo or in-vitro proof of concept studies using phenotypic data to&#xD;
           identify patient populations likely to benefit in future randomized controlled trials&#xD;
&#xD;
      This is an observational cohort study that will aim to identify patient subgroups and link&#xD;
      these with meaningful clinical outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Bronchiectasis is a common disabling and heterogeneous disease that has been&#xD;
      neglected in terms of basic and clinical research. Recent controlled trials have failed to&#xD;
      achieve their primary end-points, likely because the optimal patient population to benefit&#xD;
      from antibiotic, mucoactive and anti-inflammatory drugs has not been identified. This study&#xD;
      aims to explore the clinical, microbiological, inflammatory and functional heterogeneity of&#xD;
      the disease with the aim of identifying patient endotypes for stratified medicine.&#xD;
&#xD;
      Study aims and objectives&#xD;
&#xD;
        1. To determine the molecular endotypes of bronchiectasis during stable disease&#xD;
&#xD;
        2. To determine the causes and inflammatory profiles of bronchiectasis exacerbations&#xD;
&#xD;
        3. To validate candidate biomarkers of stable and exacerbation endotypes to use in&#xD;
           stratified medicine&#xD;
&#xD;
        4. To perform in-vivo or in-vitro proof of concept studies using phenotypic data to&#xD;
           identify patient populations likely to benefit in future randomized controlled trials&#xD;
           Study Design: Observational Cohort study&#xD;
&#xD;
      Study methods:&#xD;
&#xD;
      Patients with bronchiectasis will be recruited into an observational study, the objectives of&#xD;
      which will be to:&#xD;
&#xD;
      Aim 1 will define and validate endotypes of stable bronchiectasis by studying up to 1000&#xD;
      patients with bronchiectasis. Clinical data, sputum microbiome, sputum proteomics, and&#xD;
      systemic and sputum inflammatory marker measurement will be incorporated for analysis. A&#xD;
      sub-study (n=200) will be performed using air liquid interface culture of primary airway&#xD;
      epithelial cells. Patients will have brushings of the inferior nasal turbinate with&#xD;
      assessment of % ciliation, ciliary beat frequency and pattern by high speed video microscopy&#xD;
      before and after culture.&#xD;
&#xD;
      Aim 2 will replicate the phenotyping approach to stable patients with 160 patients during&#xD;
      exacerbation. This will identify changes from baseline in microbiota, proteomic and other&#xD;
      markers associated with onset of exacerbation and allow classification of clusters of&#xD;
      exacerbation.&#xD;
&#xD;
      Aim 3, we will externally validate candidate phenotype/endotypes in registered ethically&#xD;
      approved external biobanks and aim to demonstrate that validated markers to be linked to&#xD;
      potential treatment responses for use in stratified medicine trials.&#xD;
&#xD;
      In total we will recruit 1000 patients for study. These patients will attend the Clinical&#xD;
      Research Centre at one of the participating study centres at least once and undergo sampling&#xD;
      along with collecting of clinical data. Patients will be asked to consent for their samples&#xD;
      to be linked to data held on the EMBARC registry.&#xD;
&#xD;
      Nature of outputs and outcomes/results expected:&#xD;
&#xD;
      This study will aim to establish detailed endotypes in bronchiectasis which can guide&#xD;
      response to treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 1, 2019</start_date>
  <completion_date type="Anticipated">February 1, 2027</completion_date>
  <primary_completion_date type="Anticipated">February 1, 2027</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>Frequency of exacerbations</measure>
    <time_frame>up to 3 years</time_frame>
    <description>Worsening of respiratory symptoms as defined by the EMBARC/BRR definition- Eur Respir J. 2017 Jun 8;49(6). pii: 1700051.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to first exacerbation</measure>
    <time_frame>3 years</time_frame>
    <description>Time to first event after enrolment as defined by the EMBARC/BRR definition- Eur Respir J. 2017 Jun 8;49(6). pii: 1700051.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life- the quality of life bronchiectasis questionnaire (QOL-B)</measure>
    <time_frame>3 years</time_frame>
    <description>Validated questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life- the St Georges Respiratory Questionnaire (SGRQ)</measure>
    <time_frame>3 years</time_frame>
    <description>Validated questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life- The Bronchiectasis impact measure (BIM)</measure>
    <time_frame>3 years</time_frame>
    <description>Questionnaire undergoing validation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life- The Bronchiectasis Health Questionnaire (BHQ)</measure>
    <time_frame>3 years</time_frame>
    <description>Validated questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Forced expiratory volume in 1 second (FEV1)</measure>
    <time_frame>3 years</time_frame>
    <description>Spirometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of disease (the bronchiectasis severity index)</measure>
    <time_frame>3 years</time_frame>
    <description>Validated severity assessment tool</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospitalisation for severe exacerbations</measure>
    <time_frame>3 years</time_frame>
    <description>Admission to hospital for an exacerbation meeting the EMBARC/BRR exacerbation definition</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All cause mortality</measure>
    <time_frame>3 years</time_frame>
    <description>Survival during the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infection with Pseudomonas aeruginosa</measure>
    <time_frame>3 years</time_frame>
    <description>Defined as isolation in sputum culture or bronchoalveolar lavage meeting the criteria for chronic infection- Ann Am Thorac Soc. 2015 Nov;12(11):1602-11.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sputum volume</measure>
    <time_frame>3 years</time_frame>
    <description>Measured in millilitres per day</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">1000</enrollment>
  <condition>Bronchiectasis Adult</condition>
  <arm_group>
    <arm_group_label>Patients with bronchiectasis</arm_group_label>
    <description>Adult patients with bronchiectasis meeting the inclusion criteria.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood, DNA Serum Sputum and sputum supernatant Urine Nasal swabs Nasal biopsy&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Adult patients with bronchiectasis&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A previous CT scan showing bronchiectasis along with compatible clinical syndrome of&#xD;
             cough, sputum production and/or recurrent respiratory tract infections.&#xD;
&#xD;
          -  A primary diagnosis of bronchiectasis made by a respiratory physician&#xD;
&#xD;
          -  At the screening visit the individual will have been clinically stable for 4 weeks&#xD;
             indicated by the lack of any treatment with antibiotics or corticosteroids for a&#xD;
             pulmonary exacerbation in the previous 4 weeks.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to give informed consent&#xD;
&#xD;
          -  &lt;18years of age&#xD;
&#xD;
          -  Patients with active tuberculosis&#xD;
&#xD;
          -  Treatment with antibiotics or corticosteroids for a pulmonary exacerbation in the&#xD;
             previous 4 weeks&#xD;
&#xD;
          -  Bronchiectasis due to cystic fibrosis&#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>James D Chalmers, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>GSK/British Lung Foundation Chair of Respiratory Research</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>James D Chalmers, MD, PhD</last_name>
    <phone>01382660111</phone>
    <email>james.chalmers@nhs.scot</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Amelia Shoemark, PhD</last_name>
    <phone>01382660111</phone>
    <email>a.shoemark@dundee.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Dundee</name>
      <address>
        <city>Dundee</city>
        <zip>DD1 9SY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>James D Chalmers, MD,PhD</last_name>
      <phone>01382660111</phone>
      <email>james.chalmers@nhs.scot</email>
    </contact>
    <contact_backup>
      <last_name>Megan Crichton, Msc</last_name>
      <phone>01382 383694</phone>
      <email>m.l.crichton@dundee.ac.uk</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>December 29, 2018</study_first_submitted>
  <study_first_submitted_qc>December 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 2, 2019</study_first_posted>
  <last_update_submitted>March 19, 2023</last_update_submitted>
  <last_update_submitted_qc>March 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Dundee</investigator_affiliation>
    <investigator_full_name>James Chalmers</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>Bronchiectasis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data from EMBARC supported studies will be made available to researchers. Application for EMBARC data can be made on our website. Further information is available at www.bronchiectasis.eu/dataaccess</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>Available following the study subject to approval by the scientific committee as detailed at www.bronchiectasis.eu/dataaccess</ipd_time_frame>
    <ipd_access_criteria>Approval of an analysis protocol by an independent scientific committee</ipd_access_criteria>
  </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/NCT03791086
org study id: 2017RC11
nct id: NCT03791086
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Bronchiectasis is a complex heterogeneous disorder. Treatment is challenging and many recent
      randomized controlled trials have been negative. It is believed that bronchiectasis as a
      broad diagnosis incorporates multiple different patient subgroups (also known as phenotypes)
      and molecular entities (referred to as endotypes). This study aims to phenotype and endotype
      bronchiectasis during stable disease and exacerbations, to develop strategies for
      personalised medicine.

      Primary Objective To determine molecular endotypes of bronchiectasis which can guide response
      to treatment.

      Secondary Objectives

        1. To determine molecular endotypes of stable bronchiectasis

        2. To determine the causes and inflammatory profiles of bronchiectasis exacerbations

        3. To validate candidate biomarkers of stable and exacerbation endotypes to use in
           stratified medicine

        4. To perform in-vivo or in-vitro proof of concept studies using phenotypic data to
           identify patient populations likely to benefit in future randomized controlled trials

      This is an observational cohort study that will aim to identify patient subgroups and link
      these with meaningful clinical outcomes.
Background: Bronchiectasis is a common disabling and heterogeneous disease that has been
      neglected in terms of basic and clinical research. Recent controlled trials have failed to
      achieve their primary end-points, likely because the optimal patient population to benefit
      from antibiotic, mucoactive and anti-inflammatory drugs has not been identified. This study
      aims to explore the clinical, microbiological, inflammatory and functional heterogeneity of
      the disease with the aim of identifying patient endotypes for stratified medicine.

      Study aims and objectives

        1. To determine the molecular endotypes of bronchiectasis during stable disease

        2. To determine the causes and inflammatory profiles of bronchiectasis exacerbations

        3. To validate candidate biomarkers of stable and exacerbation endotypes to use in
           stratified medicine

        4. To perform in-vivo or in-vitro proof of concept studies using phenotypic data to
           identify patient populations likely to benefit in future randomized controlled trials
           Study Design: Observational Cohort study

      Study methods:

      Patients with bronchiectasis will be recruited into an observational study, the objectives of
      which will be to:

      Aim 1 will define and validate endotypes of stable bronchiectasis by studying up to 1000
      patients with bronchiectasis. Clinical data, sputum microbiome, sputum proteomics, and
      systemic and sputum inflammatory marker measurement will be incorporated for analysis. A
      sub-study (n=200) will be performed using air liquid interface culture of primary airway
      epithelial cells. Patients will have brushings of the inferior nasal turbinate with
      assessment of % ciliation, ciliary beat frequency and pattern by high speed video microscopy
      before and after culture.

      Aim 2 will replicate the phenotyping approach to stable patients with 160 patients during
      exacerbation. This will identify changes from baseline in microbiota, proteomic and other
      markers associated with onset of exacerbation and allow classification of clusters of
      exacerbation.

      Aim 3, we will externally validate candidate phenotype/endotypes in registered ethically
      approved external biobanks and aim to demonstrate that validated markers to be linked to
      potential treatment responses for use in stratified medicine trials.

      In total we will recruit 1000 patients for study. These patients will attend the Clinical
      Research Centre at one of the participating study centres at least once and undergo sampling
      along with collecting of clinical data. Patients will be asked to consent for their samples
      to be linked to data held on the EMBARC registry.

      Nature of outputs and outcomes/results expected:

      This study will aim to establish detailed endotypes in bronchiectasis which can guide
      response to treatment.
observational model: Cohort
time perspective: Prospective
measure: Frequency of exacerbations
time frame: up to 3 years
description: Worsening of respiratory symptoms as defined by the EMBARC/BRR definition- Eur Respir J. 2017 Jun 8;49(6). pii: 1700051.
measure: Time to first exacerbation
time frame: 3 years
description: Time to first event after enrolment as defined by the EMBARC/BRR definition- Eur Respir J. 2017 Jun 8;49(6). pii: 1700051.
measure: Quality of life- the quality of life bronchiectasis questionnaire (QOL-B)
time frame: 3 years
description: Validated questionnaire
measure: Quality of life- the St Georges Respiratory Questionnaire (SGRQ)
time frame: 3 years
description: Validated questionnaire
measure: Quality of life- The Bronchiectasis impact measure (BIM)
time frame: 3 years
description: Questionnaire undergoing validation
measure: Quality of life- The Bronchiectasis Health Questionnaire (BHQ)
time frame: 3 years
description: Validated questionnaire
measure: Forced expiratory volume in 1 second (FEV1)
time frame: 3 years
description: Spirometry
measure: Severity of disease (the bronchiectasis severity index)
time frame: 3 years
description: Validated severity assessment tool
measure: Hospitalisation for severe exacerbations
time frame: 3 years
description: Admission to hospital for an exacerbation meeting the EMBARC/BRR exacerbation definition
measure: All cause mortality
time frame: 3 years
description: Survival during the study
measure: Infection with Pseudomonas aeruginosa
time frame: 3 years
description: Defined as isolation in sputum culture or bronchoalveolar lavage meeting the criteria for chronic infection- Ann Am Thorac Soc. 2015 Nov;12(11):1602-11.
measure: Sputum volume
time frame: 3 years
description: Measured in millilitres per day
arm group label: Patients with bronchiectasis
description: Adult patients with bronchiectasis meeting the inclusion criteria.
Whole blood, DNA Serum Sputum and sputum supernatant Urine Nasal swabs Nasal biopsy
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: James D Chalmers, MD, PhD
role: Principal Investigator
affiliation: GSK/British Lung Foundation Chair of Respiratory Research
last name: James D Chalmers, MD, PhD
phone: 01382660111
email: james.chalmers@nhs.scot
last name: Amelia Shoemark, PhD
phone: 01382660111
email: a.shoemark@dundee.ac.uk
facility: 
status: Recruiting
contact: 
contact backup: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: University of Dundee
investigator full name: James Chalmers
investigator title: Professor
mesh term: Bronchiectasis
sharing ipd: Yes
ipd description: Data from EMBARC supported studies will be made available to researchers. Application for EMBARC data can be made on our website. Further information is available at www.bronchiectasis.eu/dataaccess
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: Available following the study subject to approval by the scientific committee as detailed at www.bronchiectasis.eu/dataaccess
ipd access criteria: Approval of an analysis protocol by an independent scientific committee