<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/NCT03750734</url>
  </required_header>
  <id_info>
    <org_study_id>P02437</org_study_id>
    <nct_id>NCT03750734</nct_id>
  </id_info>
  <brief_title>Target Validation and Discovery in Idiopathic Bronchiectasis</brief_title>
  <official_title>Target Validation and Discovery in Idiopathic Bronchiectasis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Papworth Hospital NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Papworth Hospital NHS Foundation Trust</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 long-term lung condition where the airways become abnormally enlarged,&#xD;
      leading to a build-up of mucus and inflammation that makes the lungs more susceptible to&#xD;
      recurrent infection. Patients with bronchiectasis have subtle abnormalities in the way their&#xD;
      airway cells respond to infection that are, in part, responsible for the development of their&#xD;
      condition. At present there are no licensed treatments for bronchiectasis.&#xD;
&#xD;
      This study will aim to characterise in depth some of these abnormalities with a view to&#xD;
      future studies that will try to develop treatments that can directly target those&#xD;
      abnormalities at a molecular level.&#xD;
&#xD;
      Patients known to have bronchiectasis who have provided written informed consent will be&#xD;
      enrolled alongside healthy volunteers and patients with chronic obstructive pulmonary disease&#xD;
      and cystic fibrosis, for comparison. Participants will give a blood sample and have a&#xD;
      bronchoscopy. This is a thin telescopic tube, passed through the nose or mouth, under&#xD;
      sedation, into the airways that will allow a sample of bronchial epithelial cells to be&#xD;
      taken.&#xD;
&#xD;
      The main objective of the study is to achieve a greater understanding of some of the key&#xD;
      biological processes/pathways and disease marker genes that play a role in the development of&#xD;
      bronchiectasis. This is important because, at present, little is known about the underlying&#xD;
      disease mechanisms and there are no licensed treatments for bronchiectasis.&#xD;
&#xD;
      The investigator's hope this in-depth characterisation of specific bronchial epithelial cell&#xD;
      abnormalities in bronchiectasis will shed light on novel targets for future drug discovery.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 10, 2019</start_date>
  <completion_date type="Actual">August 9, 2021</completion_date>
  <primary_completion_date type="Actual">August 9, 2021</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 and comparison of molecular pathways, including through gene expression analysis of airway tissues.</measure>
    <time_frame>2 years</time_frame>
    <description>Identification and comparison of molecular pathways, including through gene expression analysis of airway tissues.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Generation of air liquid interface cultures from primary bronchial epithelial cells/IPSC derived bronchial epithelial cells</measure>
    <time_frame>2 years</time_frame>
    <description>Generation of air liquid interface cultures from primary bronchial epithelial cells/IPSC derived bronchial epithelial cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional characterisation of airway epithelium</measure>
    <time_frame>2 years</time_frame>
    <description>Functional characterisation of airway epithelium</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">13</enrollment>
  <condition>Bronchiectasis</condition>
  <condition>Idiopathic Bronchiectasis</condition>
  <arm_group>
    <arm_group_label>Idiopathic bronchiectasis</arm_group_label>
    <description>Idiopathic bronchiectasis participants</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <description>Healthy volunteers</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Bronchoscopy</intervention_name>
    <description>Flexible bronchoscopy will be performed under sedation (typically a sedative such as intravenous midazolam and/or fentanyl) with local anaesthetic to the throat and vocal cords. Bronchial epithelial tissue (via bronchial brushing and biopsy forceps) and bronchial lavage samples will be taken for analysis.</description>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <arm_group_label>Idiopathic bronchiectasis</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Blood test</intervention_name>
    <description>Peripheral blood will be taken to collect peripheral blood monocytes, which will then allow the production of induced pluripotent stem cell derived bronchial epithelial tissues.</description>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <arm_group_label>Idiopathic bronchiectasis</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood, bronchial biopsy, bronchial brushings, bronchoalveolar lavage&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Secondary care respiratory clinics&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Bronchiectasis participants&#xD;
&#xD;
          1. Confirmed HRCT diagnosis of bronchiectasis in more than 1 lobe&#xD;
&#xD;
          2. Bronchiectasis not attributable to another cause, e.g. cystic fibrosis/ABPA/PCD&#xD;
&#xD;
          3. Absence of significant emphysema, COPD or asthma&#xD;
&#xD;
          4. Have provided written informed consent that they are willing to participate in the&#xD;
             study prior to sample collection&#xD;
&#xD;
        COPD participants (disease controls)&#xD;
&#xD;
          1. Confirmed diagnosis of COPD according to GOLD (Global Initiative for Chronic&#xD;
             Obstructive Lung Disease) criteria (FEV1/FVC ratio &lt; 0.70)&#xD;
&#xD;
          2. Absence of significant bronchiectasis on HRCT&#xD;
&#xD;
          3. Have provided written informed consent that they are willing to participate in the&#xD;
             study prior to sample collection&#xD;
&#xD;
        Cystic fibrosis participants (disease controls)&#xD;
&#xD;
          1. Have a confirmed diagnosis of cystic fibrosis&#xD;
&#xD;
          2. Have provided written informed consent that they are willing to participate in the&#xD;
             study prior to sample collection&#xD;
&#xD;
        Healthy controls&#xD;
&#xD;
          1. No history or diagnosis of clinically significant lung disease&#xD;
&#xD;
          2. Be a non-smoker for &gt; 1 year at screening and have &lt; 5 pack year history of smoking&#xD;
&#xD;
          3. Have provided written informed consent that they are willing to participate in the&#xD;
             study prior to sample collection&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any clinically significant acute illness, including recent exacerbation of lung&#xD;
             disease requiring treatment with oral or intravenous antibiotics, in 6 weeks prior to&#xD;
             screening&#xD;
&#xD;
          2. Any contraindication to safe bronchoscopy as judged by CI or clinical team (FEV1 &lt; 30%&#xD;
             predicted, oxygen saturations &lt; 92% on room air etc.)&#xD;
&#xD;
          3. Any clinically significant bleeding disorder or use of anticoagulant/antiplatelet&#xD;
             therapy that could place participants at risk of bleeding&#xD;
&#xD;
          4. Any contraindication to sedation or local anaesthetic medications used for&#xD;
             bronchoscopy&#xD;
&#xD;
          5. Current smoking within 6 months prior to screening (defined as someone who has smoked&#xD;
             at least one cigarette per day (or pipe, cigar, or cannabis) for ≥ 30 days within 6&#xD;
             months prior to screening)&#xD;
&#xD;
          6. Acute MI, acute stroke or major surgery within 6 months prior to screening&#xD;
&#xD;
          7. History of uncontrolled ischaemic heart disease that place participants at risk during&#xD;
             bronchoscopy&#xD;
&#xD;
          8. History of ventilatory failure or hypercapnia that may complicate bronchoscopy&#xD;
&#xD;
          9. Any known active tuberculous or non-tuberculous mycobacterial infection&#xD;
&#xD;
         10. Any use of oral corticosteroids within 4 weeks of screening&#xD;
&#xD;
         11. Any systemic immunomodulatory or immunosuppressive therapy within 3 months of&#xD;
             screening&#xD;
&#xD;
         12. Known current malignancy or current evaluation for a potential malignancy&#xD;
&#xD;
         13. Any other clinically significant medical disease that is uncontrolled despite&#xD;
             treatment, that is likely, in the opinion of the investigators, to impact the&#xD;
             patient's ability to safely participate in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dr W Flowers</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal Papworth Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Royal Papworth Hospital</name>
      <address>
        <city>Cambridge</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>November 20, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</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">April 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </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>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/NCT03750734
org study id: P02437
nct id: NCT03750734
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Bronchiectasis is a long-term lung condition where the airways become abnormally enlarged,
      leading to a build-up of mucus and inflammation that makes the lungs more susceptible to
      recurrent infection. Patients with bronchiectasis have subtle abnormalities in the way their
      airway cells respond to infection that are, in part, responsible for the development of their
      condition. At present there are no licensed treatments for bronchiectasis.

      This study will aim to characterise in depth some of these abnormalities with a view to
      future studies that will try to develop treatments that can directly target those
      abnormalities at a molecular level.

      Patients known to have bronchiectasis who have provided written informed consent will be
      enrolled alongside healthy volunteers and patients with chronic obstructive pulmonary disease
      and cystic fibrosis, for comparison. Participants will give a blood sample and have a
      bronchoscopy. This is a thin telescopic tube, passed through the nose or mouth, under
      sedation, into the airways that will allow a sample of bronchial epithelial cells to be
      taken.

      The main objective of the study is to achieve a greater understanding of some of the key
      biological processes/pathways and disease marker genes that play a role in the development of
      bronchiectasis. This is important because, at present, little is known about the underlying
      disease mechanisms and there are no licensed treatments for bronchiectasis.

      The investigator's hope this in-depth characterisation of specific bronchial epithelial cell
      abnormalities in bronchiectasis will shed light on novel targets for future drug discovery.
observational model: Cohort
time perspective: Prospective
measure: Identification and comparison of molecular pathways, including through gene expression analysis of airway tissues.
time frame: 2 years
description: Identification and comparison of molecular pathways, including through gene expression analysis of airway tissues.
measure: Generation of air liquid interface cultures from primary bronchial epithelial cells/IPSC derived bronchial epithelial cells
time frame: 2 years
description: Generation of air liquid interface cultures from primary bronchial epithelial cells/IPSC derived bronchial epithelial cells
measure: Functional characterisation of airway epithelium
time frame: 2 years
description: Functional characterisation of airway epithelium
arm group label: Idiopathic bronchiectasis
description: Idiopathic bronchiectasis participants
arm group label: Healthy volunteers
description: Healthy volunteers
intervention type: Diagnostic Test
intervention name: Bronchoscopy
description: Flexible bronchoscopy will be performed under sedation (typically a sedative such as intravenous midazolam and/or fentanyl) with local anaesthetic to the throat and vocal cords. Bronchial epithelial tissue (via bronchial brushing and biopsy forceps) and bronchial lavage samples will be taken for analysis.
arm group label: Healthy volunteers
arm group label: Idiopathic bronchiectasis
intervention type: Diagnostic Test
intervention name: Blood test
description: Peripheral blood will be taken to collect peripheral blood monocytes, which will then allow the production of induced pluripotent stem cell derived bronchial epithelial tissues.
arm group label: Healthy volunteers
arm group label: Idiopathic bronchiectasis
Whole blood, bronchial biopsy, bronchial brushings, bronchoalveolar lavage
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Dr W Flowers
role: Principal Investigator
affiliation: Royal Papworth Hospital
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Bronchiectasis
sharing ipd: No