<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/NCT03010566</url>
  </required_header>
  <id_info>
    <org_study_id>215696</org_study_id>
    <nct_id>NCT03010566</nct_id>
  </id_info>
  <brief_title>Lung Volume Reduction Coil Microbiome Study</brief_title>
  <acronym>LVRC-Micro</acronym>
  <official_title>Studying the Microbiome of the Lung in Patients Treated With Endobronchial Lung Volume Reduction Coils for Emphysema</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Royal Brompton &amp; Harefield NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Royal Brompton &amp; Harefield 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>
      Studying the microbiome of the lung in patients treated with endobronchial lung volume&#xD;
      reduction coils for emphysema&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with severe emphysema and hyperinflation can benefit from lung volume reduction&#xD;
      techniques designed to reduce gas trapping, improve air flow, and restore more natural chest&#xD;
      wall and lung mechanics. The best evidence exists for lung volume reduction surgery (LVRS),&#xD;
      but more recently there has been increasing interest in, and use of, bronchoscopic lung&#xD;
      volume reduction (BLVR) techniques. One of the more intriguing methods has been the use of&#xD;
      endobronchial lung volume reduction coils (LVRCs), nitinol wires which when deployed in the&#xD;
      lung take up their preformed shape similar to that of a tennis ball seam, and seem to work&#xD;
      both by mechanical compression of lung tissue and by replacing some of the elastic recoil&#xD;
      forces that are lost when there is emphysematous destruction of lung tissue. Treatment aims&#xD;
      to place 10 coils in each upper lobe in 2 procedures separated by 1-3 months.&#xD;
&#xD;
      A number of studies on the use of LVRCs have now been published, but most of these provide&#xD;
      only relatively short term follow-up and safety data. Fairly widespread clinical use of the&#xD;
      LVRC is now occurring in Germany, however. It is now being increasingly recognised that a&#xD;
      minority of patients treated with LVRCs (approximately 5-10%) develop dense consolidation&#xD;
      around one or more of their devices, with the development of significant cavitation in some&#xD;
      of these patients. At least 1 death has been attributed to decline associated with the&#xD;
      development of such changes, and a number of other patients have now developed infection with&#xD;
      persistent and resistant organisms. Unlike endobronchial valves (currently the most widely&#xD;
      used of the BLVR devices), patients are told that LVRC treatment is permanent and that the&#xD;
      devices cannot be removed after implantation, something which obviously has implications if&#xD;
      devices become infected or colonised with micro-organisms.&#xD;
&#xD;
      The lung microbiome is the complete collection of microorganisms that inhabit the lung,&#xD;
      including bacteria, viruses, and fungi. Studies have demonstrated the importance of&#xD;
      microorganisms in the pathogenesis of chronic obstructive pulmonary disease (COPD), and in&#xD;
      driving exacerbations and loss of lung function, and the lungs of patients with severe COPD&#xD;
      (those potentially suitable for LVRC treatment) contain a different community of bacteria to&#xD;
      those of healthy people. Culture-independent molecular techniques are now available for&#xD;
      precise cataloguing of the lung microbiome, with results that are far more detailed and&#xD;
      informative than standard culture techniques. By DNA sequencing the 16S rRNA gene and using&#xD;
      it as a barcode to identify all bacterial organisms in any given sample and also their&#xD;
      relative proportions, a much broader, less selective group of bacteria can be assayed.&#xD;
&#xD;
      The bilateral sequential nature of LVRC treatment provides a unique opportunity for the&#xD;
      collection of multiple samples from each patient at different time points in their treatment,&#xD;
      and thus to track changes in the lung microbiome that may be caused by LVRC implantation. It&#xD;
      is now our practice to perform a bronchoscopy 6 months after initial treatment in all&#xD;
      patients who have undergone BLVR (LVRCs, endobronchial valves, thermal vapour ablation) in&#xD;
      order to monitor for device migration, granulation tissue formation, and to obtain specimens&#xD;
      for bacterial culture. This therefore means that LVRC patients undergo bronchoscopy on 3&#xD;
      occasions, spaced approximately 3 months apart.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 30, 2017</start_date>
  <completion_date type="Anticipated">January 2020</completion_date>
  <primary_completion_date type="Anticipated">January 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in the microbiome of the lungs in patients treated with lung volume reduction coils (LVRCs).</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation between signals from 16S rRNA gene-sequencing analysis at baseline and infective complications following LVRC treatment.</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genome sequencing of dominant pathogens to determine virulence factors.</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genome sequencing of dominant pathogens to determine antibiotic resistance.</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genome sequencing of dominant pathogens for strain-level identification.</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <condition>Emphysema</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Oropharyngeal swab, Broncho-alveolar lavage, Bronchial brushings&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with severe emphysema who are scheduled to undergo endobronchial lung volume&#xD;
        reduction coils insertion&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Scheduled for lung volume reduction coil treatment for the management of severe&#xD;
             emphysema&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unwilling or unable to sign the informed consent form&#xD;
&#xD;
          -  Patients with known Category 3 Organisms as per the Advisory Committee on Dangerous&#xD;
             Pathogens (ACDP) for example, Tuberculosis or Human Immunodeficiency Virus.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Samuel V Kemp, MBBS MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal Brompton &amp; Harefields Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Samuel V Kemp, MBBS MD</last_name>
    <phone>02073518029</phone>
    <email>s.kemp@rbht.nhs.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Chelsea &amp; Westminster Hospital</name>
      <address>
        <city>London</city>
        <state>Chelsea</state>
        <zip>SW10 9NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nadia Shabbir</last_name>
      <phone>02033156684</phone>
      <email>Nadia.Shabbir@chelwest.nhs.uk</email>
    </contact>
    <investigator>
      <last_name>Pallav L Shah, MBBS MD FRCP</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal Brompton &amp; Harefields Hospital</name>
      <address>
        <city>London</city>
        <state>Fulham</state>
        <zip>SW3 6NP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Patrik Pettersson</last_name>
      <phone>02073528121</phone>
      <email>p.pettersson@rbht.nhs.uk</email>
    </contact>
    <investigator>
      <last_name>Samuel V Kemp, MBBS MD MRCP</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Pallav L Shah, MBBS MD FRCP</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>William Cookson, Professor</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Miriam Moffat, Professor</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Michael Cox, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Kozich JJ, Westcott SL, Baxter NT, Highlander SK, Schloss PD. Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the MiSeq Illumina sequencing platform. Appl Environ Microbiol. 2013 Sep;79(17):5112-20. doi: 10.1128/AEM.01043-13. Epub 2013 Jun 21.</citation>
    <PMID>23793624</PMID>
  </reference>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>December 20, 2016</study_first_submitted>
  <study_first_submitted_qc>January 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>April 22, 2019</last_update_submitted>
  <last_update_submitted_qc>April 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lung volume reduction coil</keyword>
  <keyword>Lung Microbiome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
    <mesh_term>Pulmonary Emphysema</mesh_term>
    <mesh_term>Emphysema</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/NCT03010566
org study id: 215696
nct id: NCT03010566
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Studying the microbiome of the lung in patients treated with endobronchial lung volume
      reduction coils for emphysema
Patients with severe emphysema and hyperinflation can benefit from lung volume reduction
      techniques designed to reduce gas trapping, improve air flow, and restore more natural chest
      wall and lung mechanics. The best evidence exists for lung volume reduction surgery (LVRS),
      but more recently there has been increasing interest in, and use of, bronchoscopic lung
      volume reduction (BLVR) techniques. One of the more intriguing methods has been the use of
      endobronchial lung volume reduction coils (LVRCs), nitinol wires which when deployed in the
      lung take up their preformed shape similar to that of a tennis ball seam, and seem to work
      both by mechanical compression of lung tissue and by replacing some of the elastic recoil
      forces that are lost when there is emphysematous destruction of lung tissue. Treatment aims
      to place 10 coils in each upper lobe in 2 procedures separated by 1-3 months.

      A number of studies on the use of LVRCs have now been published, but most of these provide
      only relatively short term follow-up and safety data. Fairly widespread clinical use of the
      LVRC is now occurring in Germany, however. It is now being increasingly recognised that a
      minority of patients treated with LVRCs (approximately 5-10%) develop dense consolidation
      around one or more of their devices, with the development of significant cavitation in some
      of these patients. At least 1 death has been attributed to decline associated with the
      development of such changes, and a number of other patients have now developed infection with
      persistent and resistant organisms. Unlike endobronchial valves (currently the most widely
      used of the BLVR devices), patients are told that LVRC treatment is permanent and that the
      devices cannot be removed after implantation, something which obviously has implications if
      devices become infected or colonised with micro-organisms.

      The lung microbiome is the complete collection of microorganisms that inhabit the lung,
      including bacteria, viruses, and fungi. Studies have demonstrated the importance of
      microorganisms in the pathogenesis of chronic obstructive pulmonary disease (COPD), and in
      driving exacerbations and loss of lung function, and the lungs of patients with severe COPD
      (those potentially suitable for LVRC treatment) contain a different community of bacteria to
      those of healthy people. Culture-independent molecular techniques are now available for
      precise cataloguing of the lung microbiome, with results that are far more detailed and
      informative than standard culture techniques. By DNA sequencing the 16S rRNA gene and using
      it as a barcode to identify all bacterial organisms in any given sample and also their
      relative proportions, a much broader, less selective group of bacteria can be assayed.

      The bilateral sequential nature of LVRC treatment provides a unique opportunity for the
      collection of multiple samples from each patient at different time points in their treatment,
      and thus to track changes in the lung microbiome that may be caused by LVRC implantation. It
      is now our practice to perform a bronchoscopy 6 months after initial treatment in all
      patients who have undergone BLVR (LVRCs, endobronchial valves, thermal vapour ablation) in
      order to monitor for device migration, granulation tissue formation, and to obtain specimens
      for bacterial culture. This therefore means that LVRC patients undergo bronchoscopy on 3
      occasions, spaced approximately 3 months apart.
observational model: Other
time perspective: Prospective
measure: Change in the microbiome of the lungs in patients treated with lung volume reduction coils (LVRCs).
time frame: 6 months
measure: Correlation between signals from 16S rRNA gene-sequencing analysis at baseline and infective complications following LVRC treatment.
time frame: 6 months
measure: Genome sequencing of dominant pathogens to determine virulence factors.
time frame: 6 months
measure: Genome sequencing of dominant pathogens to determine antibiotic resistance.
time frame: 6 months
measure: Genome sequencing of dominant pathogens for strain-level identification.
time frame: 6 months
Oropharyngeal swab, Broncho-alveolar lavage, Bronchial brushings
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Samuel V Kemp, MBBS MD
role: Principal Investigator
affiliation: Royal Brompton & Harefields Hospital
last name: Samuel V Kemp, MBBS MD
phone: 02073518029
email: s.kemp@rbht.nhs.uk
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: United Kingdom
citation: Kozich JJ, Westcott SL, Baxter NT, Highlander SK, Schloss PD. Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the MiSeq Illumina sequencing platform. Appl Environ Microbiol. 2013 Sep;79(17):5112-20. doi: 10.1128/AEM.01043-13. Epub 2013 Jun 21.
PMID: 23793624
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Pulmonary Emphysema
mesh term: Emphysema
sharing ipd: No