<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/NCT01701869</url>
  </required_header>
  <id_info>
    <org_study_id>RMH MED 1055</org_study_id>
    <secondary_id>RESP RES-001 (117027)</secondary_id>
    <nct_id>NCT01701869</nct_id>
  </id_info>
  <brief_title>Microbiology &amp; Immunology of the Chronically-inflamed Airway</brief_title>
  <acronym>MICA</acronym>
  <official_title>Microbiology &amp; Immunology of the Chronically-inflamed Airway (RESP RES-001 (117027))</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital Southampton NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital Southampton NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death and the&#xD;
      only one of the common causes that is still rising. The main effects of the disease are the&#xD;
      destruction and inflammation of lung tissue rendering breathing difficult. COPD has&#xD;
      significant effects on the quality of life of sufferers and the disease is predicted to be&#xD;
      the fifth most common cause of disability in the world by 2020. Patients with COPD are prone&#xD;
      to periods of worsening disease symptoms, known as exacerbations, which are often caused by&#xD;
      viral and bacterial infections of the lung and current vaccines appear to have little&#xD;
      efficacy in limiting these exacerbations. The loss of lung function caused by infectious&#xD;
      exacerbations is irreversible and patients who frequently exacerbate experience more rapid&#xD;
      disease progression. Nontypeable Haemophilus influenzae (NTHi) is a major bacterial species&#xD;
      that colonises the airways and causes exacerbations in COPD. With the development of more&#xD;
      sensitive molecular techniques it has been possible to ascertain that it is the acquisition&#xD;
      of new strains of NTHi that correlate strongly with exacerbations. However, not all patients&#xD;
      with COPD have NTHi in their lungs and the question remains as to why some COPD patients are&#xD;
      susceptible to such infections. This study aims to answer this question by comparing the&#xD;
      airways of COPD patients who are colonized by NTHi and those who are not to analyse whether&#xD;
      the levels of protective antibodies in the lungs and the function of the immune cells in the&#xD;
      NTHi colonized airway are reduced. Moreover, we aim to correlate this reduction in immunity&#xD;
      with areas of lung damage ascertained by high resolution computed tomography. The aim of this&#xD;
      research is to better understand this apparent deficiency in airway immunity as this is&#xD;
      likely to impact on vaccine efficacy in COPD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Detection of NTHi in radiologically-designated areas of disease in the COPD lung</measure>
    <time_frame>Within 2 years of enrollment</time_frame>
    <description>The overall aim of this project is to enhance our understanding of the relevance of local immunity to protection of the airway from viral and bacterial infection and thus development of vaccines against such organisms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measurement of NTHi specific antibody levels in lavage derived from radiologically-designated areas of disease in the COPD lung</measure>
    <time_frame>Within 2 years of enrollment</time_frame>
    <description>The overall aim of this project is to enhance our understanding of the relevance of local immunity to protection of the airway from viral and bacterial infection and thus development of vaccines against such organisms.</description>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">57</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease (COPD)</condition>
  <arm_group>
    <arm_group_label>NTHi positive</arm_group_label>
    <description>No intervention, this is an observational study</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NTHi negative</arm_group_label>
    <description>No intervention, this is an observational study</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Control</arm_group_label>
    <description>No intervention, this is an observational study</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum, plasma, inflammatory cell RNA/DNA, nasopharyngeal swabs, urine, sputum supernatants,&#xD;
      sputum cells, bronchial epitehlial cells, BAL supernatants, BAL cells, bronchial biopsies.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Volunteers will be recruited from General Practice in the form of patient screening&#xD;
        clinics,and GP Mailshot. Quitters and pulmonary rehabilitation, would also be approached.&#xD;
        The Respiratory Centre, patient support groups, and outpatient departments and wards, would&#xD;
        also be areas of recruitment.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects who the investigator believes can and will comply with the requirements of&#xD;
             the protocol.&#xD;
&#xD;
          -  Written informed consent obtained from the subject.&#xD;
&#xD;
          -  Male or female subjects between, and including, 40 and 85 years of age, at the time of&#xD;
             consent.&#xD;
&#xD;
          -  Subjects with confirmed diagnosis of COPD (based on postbronchodilator spirometry).&#xD;
             [GOLD, 2009] with FEV1 of &gt;80% (mild COPD) or &gt;50% but ≤80% (moderate COPD) of&#xD;
             predicted normal and FEV1/FVC&lt;0.7&#xD;
&#xD;
          -  Subjects have mild or moderate COPD, according to Global Initiative for Chronic&#xD;
             Obstructive Lung Disease (GOLD) staging [GOLD, 2009].&#xD;
&#xD;
          -  Subjects have a current or prior history of ≥10 pack years of cigarette smoking.&#xD;
             Former smokers are defined as those who have stopped smoking for at least 6 months.&#xD;
             Number of pack years = (number of cigarettes per day/20) x number of years smoked.&#xD;
&#xD;
          -  Subjects with recent COPD exacerbations, in stable condition, and having stopped&#xD;
             antibiotics, can be enrolled one month post exacerbation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject also has a confirmed diagnosis of asthma (as only cause of obstructive&#xD;
             respiratory disorder), cystic fibrosis, pneumonia risk factors (e.g., HIV, Lupus,&#xD;
             Parkinson's, Myasthenia Gravis) or other respiratory disorders (e.g., tuberculosis,&#xD;
             lung cancer).&#xD;
&#xD;
          -  Subjects having undergone lung surgery&#xD;
&#xD;
          -  Subject has a α1-antitrypsin deficiency as underlying cause of COPD.&#xD;
&#xD;
          -  Subject who experienced a moderate or severe COPD exacerbation not resolved at least 1&#xD;
             month prior to enrolment visit and at least 30 days following the last dose of oral&#xD;
             corticosteroids (subjects can be enrolled when their acute AECOPD or pneumonia has&#xD;
             resolved).&#xD;
&#xD;
          -  Subject using any antibacterial, antiviral or respiratory investigational drug or&#xD;
             relevant vaccine up to 30 days prior to the enrolment visit.&#xD;
&#xD;
          -  Subject has other conditions that the principal investigator judges may interfere with&#xD;
             the study findings, such as:&#xD;
&#xD;
          -  Subject at risk of noncompliance, or unable to comply with the study procedures.&#xD;
&#xD;
          -  Evidence of alcohol or drug abuse.&#xD;
&#xD;
          -  Others, as per clinical judgement&#xD;
&#xD;
          -  Women who are pregnant or lactating or are planning on becoming pregnant during the&#xD;
             study **If subject has any ONE of the above exclusion they cannot be enrolled into the&#xD;
             study**&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tom MA Wilkinson, MA MB BS MRCP PhD</last_name>
    <role>Study Director</role>
    <affiliation>University of Southampton</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Southampton University Hospital NHS Trust</name>
      <address>
        <city>Southampton</city>
        <state>Hampshire</state>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <results_reference>
    <citation>Ostridge K, Williams N, Kim V, Bennett M, Harden S, Welch L, Bourne S, Coombs NA, Elkington PT, Staples KJ, Wilkinson TM. Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD. Thorax. 2016 Feb;71(2):126-32. doi: 10.1136/thoraxjnl-2015-207428. Epub 2015 Dec 8.</citation>
    <PMID>26645414</PMID>
  </results_reference>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>October 1, 2012</study_first_submitted>
  <study_first_submitted_qc>October 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 5, 2012</study_first_posted>
  <last_update_submitted>April 13, 2016</last_update_submitted>
  <last_update_submitted_qc>April 13, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 14, 2016</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>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>June 29, 2017</submitted>
    <returned>November 27, 2017</returned>
    <submitted>May 15, 2018</submitted>
    <returned>November 28, 2018</returned>
  </pending_results>
  <!-- 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/NCT01701869
org study id: RMH MED 1055
secondary id: RESP RES-001 (117027)
nct id: NCT01701869
lead sponsor: 
collaborator: 
has dmc: No
Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death and the
      only one of the common causes that is still rising. The main effects of the disease are the
      destruction and inflammation of lung tissue rendering breathing difficult. COPD has
      significant effects on the quality of life of sufferers and the disease is predicted to be
      the fifth most common cause of disability in the world by 2020. Patients with COPD are prone
      to periods of worsening disease symptoms, known as exacerbations, which are often caused by
      viral and bacterial infections of the lung and current vaccines appear to have little
      efficacy in limiting these exacerbations. The loss of lung function caused by infectious
      exacerbations is irreversible and patients who frequently exacerbate experience more rapid
      disease progression. Nontypeable Haemophilus influenzae (NTHi) is a major bacterial species
      that colonises the airways and causes exacerbations in COPD. With the development of more
      sensitive molecular techniques it has been possible to ascertain that it is the acquisition
      of new strains of NTHi that correlate strongly with exacerbations. However, not all patients
      with COPD have NTHi in their lungs and the question remains as to why some COPD patients are
      susceptible to such infections. This study aims to answer this question by comparing the
      airways of COPD patients who are colonized by NTHi and those who are not to analyse whether
      the levels of protective antibodies in the lungs and the function of the immune cells in the
      NTHi colonized airway are reduced. Moreover, we aim to correlate this reduction in immunity
      with areas of lung damage ascertained by high resolution computed tomography. The aim of this
      research is to better understand this apparent deficiency in airway immunity as this is
      likely to impact on vaccine efficacy in COPD.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Detection of NTHi in radiologically-designated areas of disease in the COPD lung
time frame: Within 2 years of enrollment
description: The overall aim of this project is to enhance our understanding of the relevance of local immunity to protection of the airway from viral and bacterial infection and thus development of vaccines against such organisms.
measure: Measurement of NTHi specific antibody levels in lavage derived from radiologically-designated areas of disease in the COPD lung
time frame: Within 2 years of enrollment
description: The overall aim of this project is to enhance our understanding of the relevance of local immunity to protection of the airway from viral and bacterial infection and thus development of vaccines against such organisms.
arm group label: NTHi positive
description: No intervention, this is an observational study
arm group label: NTHi negative
description: No intervention, this is an observational study
arm group label: Healthy Control
description: No intervention, this is an observational study
Serum, plasma, inflammatory cell RNA/DNA, nasopharyngeal swabs, urine, sputum supernatants,
      sputum cells, bronchial epitehlial cells, BAL supernatants, BAL cells, bronchial biopsies.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 40 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Tom MA Wilkinson, MA MB BS MRCP PhD
role: Study Director
affiliation: University of Southampton
facility: 
country: United Kingdom
citation: Ostridge K, Williams N, Kim V, Bennett M, Harden S, Welch L, Bourne S, Coombs NA, Elkington PT, Staples KJ, Wilkinson TM. Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD. Thorax. 2016 Feb;71(2):126-32. doi: 10.1136/thoraxjnl-2015-207428. Epub 2015 Dec 8.
PMID: 26645414
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
submitted: June 29, 2017
returned: November 27, 2017
submitted: May 15, 2018
returned: November 28, 2018