<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/NCT02236039</url>
  </required_header>
  <id_info>
    <org_study_id>H14-00821</org_study_id>
    <nct_id>NCT02236039</nct_id>
  </id_info>
  <brief_title>COPD Originates in Polluted Air</brief_title>
  <acronym>COPA</acronym>
  <official_title>The Effects of Traffic-Related Air Pollution on Smokers at Risk for Developing COPD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of British Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of British Columbia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators are investigating the effects of traffic-related diesel exhaust on lung&#xD;
      function and the immune system in those at risk for COPD. The individual will be exposed to&#xD;
      either filtered air (FA) or carefully controlled levels of diesel exhaust (DE) in our&#xD;
      exposure chamber. Post exposure the individual will complete a steady state exercise test.&#xD;
      24h later, a procedure called bronchoscopy (whereby a thin, flexible tube is placed down the&#xD;
      throat and into the lungs) will be used so that samples can be collected from the lungs.&#xD;
      After 1 month the entire procedure will be repeated with the alternative exposure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Purpose:&#xD;
&#xD;
           To study the effects of traffic related diesel exhaust on people at risk for developing&#xD;
           COPD.&#xD;
&#xD;
        2. Hypotheses:&#xD;
&#xD;
           Hypothesis 1: An increase in proteins, in the exposed lung and blood, that are&#xD;
           associated with the pathophysiology of COPD.&#xD;
&#xD;
           Hypothesis 2: Air trapping, dyspnea, and impaired exercise tolerance. Such increases&#xD;
           will be more pronounced in those with COPD than in control subjects.&#xD;
&#xD;
        3. Justification:&#xD;
&#xD;
           The use of diesel engines is increasing because they are more fuel-efficient than&#xD;
           gasoline engines. However, diesel engines produce different emissions than gasoline&#xD;
           engines. Diesel exhaust is emitted from the tailpipe of both &quot;on-road&quot; diesel engine&#xD;
           vehicles (diesel cars, buses and trucks) and &quot;non-road&quot; diesel engines (locomotives,&#xD;
           marine vessels and some construction equipment). Diesel exhaust consists of both gaseous&#xD;
           and particulate air pollutants. People with COPD may be sensitive to air pollution; we&#xD;
           would like to know how diesel exhaust (DE) can affects the respiratory and immune&#xD;
           systems. We are not expecting that responses will be noticeable to the participant; we&#xD;
           are expecting that any responses that may occur will only be detectable through careful&#xD;
           examination of cells and tissues (e.g., bronchoalveolar lavage (fluid from lungs),&#xD;
           blood). Understanding these subtle changes will help us prevent health problems&#xD;
           associated with air pollution in the future.&#xD;
&#xD;
        4. Objectives To provide biological plausibility and deepen mechanistic understanding of&#xD;
           the emerging epidemiology suggesting a strong role for air pollution in COPD.&#xD;
&#xD;
        5. Research Methods:&#xD;
&#xD;
      This is a blinded crossover experiment between two conditions (300 µg/m³ diesel exhaust or&#xD;
      filtered air), randomized and counter-balanced to order. Data collection for each condition&#xD;
      will be separated by a 4-week washout period.&#xD;
&#xD;
      Prior to the exposure participants will: 1) complete some questionnaires, 2) undergo a set of&#xD;
      lung function tests (breathing tests), 3) undergo an incremental exercise test and 4) receive&#xD;
      a physical exam by the primary investigator. A small sample of blood and spirometry&#xD;
      measurements will also be collected for analysis.&#xD;
&#xD;
      After the exposure another series of exercise and lung function tests will be performed.&#xD;
      Blood, spirometry measurements, bronchoalveolar lavage (BAL), endobronchial brushings and&#xD;
      biopsies will also be collected for examination of cellular, functional and immunological&#xD;
      changes influencing the airways.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 27, 2014</start_date>
  <completion_date type="Actual">May 1, 2019</completion_date>
  <primary_completion_date type="Actual">May 1, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cytokine pattern</measure>
    <time_frame>24 hours</time_frame>
    <description>BAL, BW, and blood cytokines will be assessed at 24h using immunoassays</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Gene expression</measure>
    <time_frame>24 hours</time_frame>
    <description>BAL, BW, endobronchial brushings and blood will be used for gene expression. RNA will be isolated using RNeasy and supplemented by assessment of promising candidate genes by real-time RT-PCR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiopulmonary function</measure>
    <time_frame>1.5 hours</time_frame>
    <description>Cardio pulmonary function will be measured at 1.5 hours post exposure using a cardiopulmonary testing system (Vmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cell culture</measure>
    <time_frame>24 hours</time_frame>
    <description>Airway epithelial cells from the endobronchial brushings will be used for non-immortalized cell culture</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>COPD</condition>
  <arm_group>
    <arm_group_label>Filtered air</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Exposure for 2 hours to filtered air followed by a bronchoscopy 24 hours post exposure.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diesel exhaust</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Exposure for 2 hours to diesel exhaust followed by a bronchoscopy 24 hours post exposure.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Bronchoscopy</intervention_name>
    <description>Bronchoscopy with biopsy sampling, brushings and bronchoalveolar lavage (BAL) 24 hours post exposure.</description>
    <arm_group_label>Diesel exhaust</arm_group_label>
    <arm_group_label>Filtered air</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age between 40-75 years of age&#xD;
&#xD;
          2. Free of cardiovascular disease&#xD;
&#xD;
          3. Free of insulin-dependent diabetes&#xD;
&#xD;
          4. Study participants must agree to adhere to the following medication intake protocol 24&#xD;
             hours prior to study visits:&#xD;
&#xD;
               -  participants will be asked to withhold:&#xD;
&#xD;
               -  short-acting beta2-agonists (SABAs) for 4 hours prior to testing&#xD;
&#xD;
               -  long-acting beta2-agonists (LABAs) for 12 hours prior to testing if taken in an&#xD;
                  individual inhaler (different inhaler from inhaled corticosteroid inhaler)&#xD;
&#xD;
               -  LABAs and ICS for 24hrs, if those two medication groups are combined in one&#xD;
                  inhaler&#xD;
&#xD;
               -  ICS (if taken alone as a mono-therapy, or if taken with either a LABA or SABA,&#xD;
                  but in two separate inhaler), for 24 hrs.&#xD;
&#xD;
        Overall, we are looking for 15 healthy controls without a history of smoking; 20&#xD;
        individuals with a history of smoking, but who have been non-smokers for at least 6 months&#xD;
        prior to study participation; and 15 mild-moderate COPD patients (GOLD I and GOLD II).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not between the ages of 40-65 years.&#xD;
&#xD;
          -  Are pregnant, breast-feeding, or planning to get pregnant in the following 12 months.&#xD;
&#xD;
          -  Are currently using inhaled corticosteroids.&#xD;
&#xD;
          -  Are allergic to salbutamol, lidocaine, fentanyl or midazolam.&#xD;
&#xD;
          -  Are currently participating in another study that involves taking medications.&#xD;
&#xD;
          -  Have unstable COPD symptoms.&#xD;
&#xD;
          -  Have clinically significant comorbidities (i.e., coronary artery disease).&#xD;
&#xD;
          -  Have a history/clinical evidence of asthma.&#xD;
&#xD;
          -  Have contraindications to exercise testing.&#xD;
&#xD;
          -  Have a body mass index &lt;18.5.&#xD;
&#xD;
          -  Regularly use of antihistamines, non-steroidal anti-inflammatories, anticoagulants,&#xD;
             acetylsalicylic acid (ASA) or decongestants.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christopher Carlsten, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of British Columbia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of British Columbia</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 1M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Behndig AF, Mudway IS, Brown JL, Stenfors N, Helleday R, Duggan ST, Wilson SJ, Boman C, Cassee FR, Frew AJ, Kelly FJ, Sandstrom T, Blomberg A. Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans. Eur Respir J. 2006 Feb;27(2):359-65. doi: 10.1183/09031936.06.00136904.</citation>
    <PMID>16452593</PMID>
  </reference>
  <reference>
    <citation>Hsia CC, Hyde DM, Ochs M, Weibel ER; ATS/ERS Joint Task Force on Quantitative Assessment of Lung Structure. An official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am J Respir Crit Care Med. 2010 Feb 15;181(4):394-418. doi: 10.1164/rccm.200809-1522ST. No abstract available.</citation>
    <PMID>20130146</PMID>
  </reference>
  <reference>
    <citation>Gan, W. Q., J. M. FitzGerald, et al. (2013).</citation>
  </reference>
  <reference>
    <citation>Mannino DM, Buist AS. Global burden of COPD: risk factors, prevalence, and future trends. Lancet. 2007 Sep 1;370(9589):765-73. doi: 10.1016/S0140-6736(07)61380-4.</citation>
    <PMID>17765526</PMID>
  </reference>
  <reference>
    <citation>Rudell B, Ledin MC, Hammarstrom U, Stjernberg N, Lundback B, Sandstrom T. Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust. Occup Environ Med. 1996 Oct;53(10):658-62. doi: 10.1136/oem.53.10.658.</citation>
    <PMID>8943829</PMID>
  </reference>
  <reference>
    <citation>Schikowski, T., M. Adam, et al. (2014).</citation>
  </reference>
  <reference>
    <citation>McCreanor, J., P. Cullinan, et al. (2007).</citation>
  </reference>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>August 11, 2014</study_first_submitted>
  <study_first_submitted_qc>September 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2014</study_first_posted>
  <last_update_submitted>October 29, 2021</last_update_submitted>
  <last_update_submitted_qc>October 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of British Columbia</investigator_affiliation>
    <investigator_full_name>Christopher Carlsten</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Diesel exhaust</keyword>
  <keyword>Air pollution</keyword>
  <keyword>Airway responsivness</keyword>
  <!-- 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/NCT02236039
org study id: H14-00821
nct id: NCT02236039
lead sponsor: 
has dmc: No
The investigators are investigating the effects of traffic-related diesel exhaust on lung
      function and the immune system in those at risk for COPD. The individual will be exposed to
      either filtered air (FA) or carefully controlled levels of diesel exhaust (DE) in our
      exposure chamber. Post exposure the individual will complete a steady state exercise test.
      24h later, a procedure called bronchoscopy (whereby a thin, flexible tube is placed down the
      throat and into the lungs) will be used so that samples can be collected from the lungs.
      After 1 month the entire procedure will be repeated with the alternative exposure.
1. Purpose:

           To study the effects of traffic related diesel exhaust on people at risk for developing
           COPD.

        2. Hypotheses:

           Hypothesis 1: An increase in proteins, in the exposed lung and blood, that are
           associated with the pathophysiology of COPD.

           Hypothesis 2: Air trapping, dyspnea, and impaired exercise tolerance. Such increases
           will be more pronounced in those with COPD than in control subjects.

        3. Justification:

           The use of diesel engines is increasing because they are more fuel-efficient than
           gasoline engines. However, diesel engines produce different emissions than gasoline
           engines. Diesel exhaust is emitted from the tailpipe of both "on-road" diesel engine
           vehicles (diesel cars, buses and trucks) and "non-road" diesel engines (locomotives,
           marine vessels and some construction equipment). Diesel exhaust consists of both gaseous
           and particulate air pollutants. People with COPD may be sensitive to air pollution; we
           would like to know how diesel exhaust (DE) can affects the respiratory and immune
           systems. We are not expecting that responses will be noticeable to the participant; we
           are expecting that any responses that may occur will only be detectable through careful
           examination of cells and tissues (e.g., bronchoalveolar lavage (fluid from lungs),
           blood). Understanding these subtle changes will help us prevent health problems
           associated with air pollution in the future.

        4. Objectives To provide biological plausibility and deepen mechanistic understanding of
           the emerging epidemiology suggesting a strong role for air pollution in COPD.

        5. Research Methods:

      This is a blinded crossover experiment between two conditions (300 µg/m³ diesel exhaust or
      filtered air), randomized and counter-balanced to order. Data collection for each condition
      will be separated by a 4-week washout period.

      Prior to the exposure participants will: 1) complete some questionnaires, 2) undergo a set of
      lung function tests (breathing tests), 3) undergo an incremental exercise test and 4) receive
      a physical exam by the primary investigator. A small sample of blood and spirometry
      measurements will also be collected for analysis.

      After the exposure another series of exercise and lung function tests will be performed.
      Blood, spirometry measurements, bronchoalveolar lavage (BAL), endobronchial brushings and
      biopsies will also be collected for examination of cellular, functional and immunological
      changes influencing the airways.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Cytokine pattern
time frame: 24 hours
description: BAL, BW, and blood cytokines will be assessed at 24h using immunoassays
measure: Gene expression
time frame: 24 hours
description: BAL, BW, endobronchial brushings and blood will be used for gene expression. RNA will be isolated using RNeasy and supplemented by assessment of promising candidate genes by real-time RT-PCR
measure: Cardiopulmonary function
time frame: 1.5 hours
description: Cardio pulmonary function will be measured at 1.5 hours post exposure using a cardiopulmonary testing system (Vmax)
measure: Cell culture
time frame: 24 hours
description: Airway epithelial cells from the endobronchial brushings will be used for non-immortalized cell culture
arm group label: Filtered air
arm group type: Active Comparator
description: Exposure for 2 hours to filtered air followed by a bronchoscopy 24 hours post exposure.
arm group label: Diesel exhaust
arm group type: Experimental
description: Exposure for 2 hours to diesel exhaust followed by a bronchoscopy 24 hours post exposure.
intervention type: Procedure
intervention name: Bronchoscopy
description: Bronchoscopy with biopsy sampling, brushings and bronchoalveolar lavage (BAL) 24 hours post exposure.
arm group label: Diesel exhaust
arm group label: Filtered air
criteria: 
gender: All
minimum age: 40 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Christopher Carlsten, MD, MPH
role: Principal Investigator
affiliation: University of British Columbia
facility: 
country: Canada
citation: Behndig AF, Mudway IS, Brown JL, Stenfors N, Helleday R, Duggan ST, Wilson SJ, Boman C, Cassee FR, Frew AJ, Kelly FJ, Sandstrom T, Blomberg A. Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans. Eur Respir J. 2006 Feb;27(2):359-65. doi: 10.1183/09031936.06.00136904.
PMID: 16452593
citation: Hsia CC, Hyde DM, Ochs M, Weibel ER; ATS/ERS Joint Task Force on Quantitative Assessment of Lung Structure. An official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am J Respir Crit Care Med. 2010 Feb 15;181(4):394-418. doi: 10.1164/rccm.200809-1522ST. No abstract available.
PMID: 20130146
citation: Gan, W. Q., J. M. FitzGerald, et al. (2013).
citation: Mannino DM, Buist AS. Global burden of COPD: risk factors, prevalence, and future trends. Lancet. 2007 Sep 1;370(9589):765-73. doi: 10.1016/S0140-6736(07)61380-4.
PMID: 17765526
citation: Rudell B, Ledin MC, Hammarstrom U, Stjernberg N, Lundback B, Sandstrom T. Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust. Occup Environ Med. 1996 Oct;53(10):658-62. doi: 10.1136/oem.53.10.658.
PMID: 8943829
citation: Schikowski, T., M. Adam, et al. (2014).
citation: McCreanor, J., P. Cullinan, et al. (2007).
responsible party type: Principal Investigator
investigator affiliation: University of British Columbia
investigator full name: Christopher Carlsten
investigator title: Principal Investigator