<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/NCT01699204</url>
  </required_header>
  <id_info>
    <org_study_id>H08-02288</org_study_id>
    <nct_id>NCT01699204</nct_id>
  </id_info>
  <brief_title>Diesel Exhaust and Mechanism of Asthma</brief_title>
  <official_title>Effects of Diesel Exhaust on Airways</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>
      This experiment is designed to test the hypothesis that oxidative stress is responsible for&#xD;
      changes in airway responsiveness in humans exposed to diesel exhaust.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The specific aim is to test the hypothesis that diesel exhaust (DE) increases airway&#xD;
      reactivity via oxidative stress, particularly in asthmatics. To test this hypothesis, we use&#xD;
      a crossover in vivo experimental model in mild asthmatics and normal controls using a&#xD;
      state-of-the-art diesel exhaust exposure facility.&#xD;
&#xD;
      Participants took N-acetylcysteine (600 mg) or placebo capsules three times daily for six&#xD;
      days. On the final morning of supplementation, participants were exposed for 2 hours to&#xD;
      either filtered air or diesel exhaust (300 µg·m-3 of particulate matter smaller than 2.5&#xD;
      microns). Twenty-six non-smokers between 19-49 years were studied under three experimental&#xD;
      conditions (filtered air with placebo, diesel exhaust with placebo and diesel exhaust with&#xD;
      N-acetylcysteine) using randomized, double-blind, crossover design, with a two week minimum&#xD;
      washout between conditions. Methacholine challenge was performed pre-exposure (to determine&#xD;
      baseline airway responsiveness) and post-exposure (to determine the effect of exposure).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2007</start_date>
  <completion_date type="Actual">October 2011</completion_date>
  <primary_completion_date type="Actual">October 2011</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>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Human airway reactivity</measure>
    <time_frame>50 hours</time_frame>
    <description>Establish that oxidative stress is responsible for changes in human airway reactivity induced by DE (300 µg/m3 inhaled for two hours).</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Filtered air with placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Exposure for 2 hours to filtered air and placebo tablets 3 times daily for 6 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diesel exhaust with placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Exposure for 2 hours to diesel exhaust and placebo tablets 3 times daily for 6 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diesel exhaust with N-acetylcysteine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Exposure for 2 hours to diesel exhaust and N-acetylcysteine tablets (600 mg) 3 times daily for 6 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>N-acetylcysteine</intervention_name>
    <description>N-acetylcysteine 600mg taken orally 3 times daily for 6 days prior to exposure to diesel exhaust for 2 hours. The last supplement was taken the morning of the exposure</description>
    <arm_group_label>Diesel exhaust with N-acetylcysteine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Diesel exhaust</intervention_name>
    <description>A placebo tablet taken 3 times daily for 6 days prior to exposure to diesel exhaust for 2 hours. The last supplement was taken the morning of the exposure</description>
    <arm_group_label>Diesel exhaust with N-acetylcysteine</arm_group_label>
    <arm_group_label>Diesel exhaust with placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Filtered air</intervention_name>
    <description>A placebo tablet taken 3 times daily for 6 days prior to exposure to filtered air for 2 hours. The last supplement was taken the morning of the exposure</description>
    <arm_group_label>Filtered air with placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Between 19-49 years, non smokers, asthmatics, healthy controls&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smokers, pregnant or co-existing medical condition for which diesel exhaust would&#xD;
             confer significant risk (i.e. coronary artery disease)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>49 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>V5Z1M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Braman SS. The global burden of asthma. Chest. 2006 Jul;130(1 Suppl):4S-12S. doi: 10.1378/chest.130.1_suppl.4S.</citation>
    <PMID>16840363</PMID>
  </reference>
  <reference>
    <citation>Atkinson RW, Anderson HR, Sunyer J, Ayres J, Baccini M, Vonk JM, Boumghar A, Forastiere F, Forsberg B, Touloumi G, Schwartz J, Katsouyanni K. Acute effects of particulate air pollution on respiratory admissions: results from APHEA 2 project. Air Pollution and Health: a European Approach. Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1860-6. doi: 10.1164/ajrccm.164.10.2010138.</citation>
    <PMID>11734437</PMID>
  </reference>
  <reference>
    <citation>Janssen NA, Brunekreef B, van Vliet P, Aarts F, Meliefste K, Harssema H, Fischer P. The relationship between air pollution from heavy traffic and allergic sensitization, bronchial hyperresponsiveness, and respiratory symptoms in Dutch schoolchildren. Environ Health Perspect. 2003 Sep;111(12):1512-8. doi: 10.1289/ehp.6243.</citation>
    <PMID>12948892</PMID>
  </reference>
  <reference>
    <citation>Mudway IS, Stenfors N, Duggan ST, Roxborough H, Zielinski H, Marklund SL, Blomberg A, Frew AJ, Sandstrom T, Kelly FJ. An in vitro and in vivo investigation of the effects of diesel exhaust on human airway lining fluid antioxidants. Arch Biochem Biophys. 2004 Mar 1;423(1):200-12. doi: 10.1016/j.abb.2003.12.018.</citation>
    <PMID>14871482</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>Stenfors N, Nordenhall C, Salvi SS, Mudway I, Soderberg M, Blomberg A, Helleday R, Levin JO, Holgate ST, Kelly FJ, Frew AJ, Sandstrom T. Different airway inflammatory responses in asthmatic and healthy humans exposed to diesel. Eur Respir J. 2004 Jan;23(1):82-6. doi: 10.1183/09031936.03.00004603.</citation>
    <PMID>14738236</PMID>
  </reference>
  <reference>
    <citation>Hashimoto S, Gon Y, Takeshita I, Matsumoto K, Jibiki I, Takizawa H, Kudoh S, Horie T. Diesel exhaust particles activate p38 MAP kinase to produce interleukin 8 and RANTES by human bronchial epithelial cells and N-acetylcysteine attenuates p38 MAP kinase activation. Am J Respir Crit Care Med. 2000 Jan;161(1):280-5. doi: 10.1164/ajrccm.161.1.9904110.</citation>
    <PMID>10619832</PMID>
  </reference>
  <reference>
    <citation>McCreanor J, Cullinan P, Nieuwenhuijsen MJ, Stewart-Evans J, Malliarou E, Jarup L, Harrington R, Svartengren M, Han IK, Ohman-Strickland P, Chung KF, Zhang J. Respiratory effects of exposure to diesel traffic in persons with asthma. N Engl J Med. 2007 Dec 6;357(23):2348-58. doi: 10.1056/NEJMoa071535.</citation>
    <PMID>18057337</PMID>
  </reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>October 1, 2012</study_first_submitted>
  <study_first_submitted_qc>October 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2012</study_first_posted>
  <last_update_submitted>September 27, 2017</last_update_submitted>
  <last_update_submitted_qc>September 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2017</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>Air pollution</keyword>
  <keyword>Diesel exhaust</keyword>
  <keyword>Airway responsiveness</keyword>
  <keyword>Asthma</keyword>
  <keyword>Anti-oxidant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetylcysteine</mesh_term>
    <mesh_term>N-monoacetylcystine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01699204
org study id: H08-02288
nct id: NCT01699204
lead sponsor: 
has dmc: No
This experiment is designed to test the hypothesis that oxidative stress is responsible for
      changes in airway responsiveness in humans exposed to diesel exhaust.
The specific aim is to test the hypothesis that diesel exhaust (DE) increases airway
      reactivity via oxidative stress, particularly in asthmatics. To test this hypothesis, we use
      a crossover in vivo experimental model in mild asthmatics and normal controls using a
      state-of-the-art diesel exhaust exposure facility.

      Participants took N-acetylcysteine (600 mg) or placebo capsules three times daily for six
      days. On the final morning of supplementation, participants were exposed for 2 hours to
      either filtered air or diesel exhaust (300 µg·m-3 of particulate matter smaller than 2.5
      microns). Twenty-six non-smokers between 19-49 years were studied under three experimental
      conditions (filtered air with placebo, diesel exhaust with placebo and diesel exhaust with
      N-acetylcysteine) using randomized, double-blind, crossover design, with a two week minimum
      washout between conditions. Methacholine challenge was performed pre-exposure (to determine
      baseline airway responsiveness) and post-exposure (to determine the effect of exposure).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Human airway reactivity
time frame: 50 hours
description: Establish that oxidative stress is responsible for changes in human airway reactivity induced by DE (300 µg/m3 inhaled for two hours).
arm group label: Filtered air with placebo
arm group type: Placebo Comparator
description: Exposure for 2 hours to filtered air and placebo tablets 3 times daily for 6 days
arm group label: Diesel exhaust with placebo
arm group type: Active Comparator
description: Exposure for 2 hours to diesel exhaust and placebo tablets 3 times daily for 6 days
arm group label: Diesel exhaust with N-acetylcysteine
arm group type: Experimental
description: Exposure for 2 hours to diesel exhaust and N-acetylcysteine tablets (600 mg) 3 times daily for 6 days
intervention type: Dietary Supplement
intervention name: N-acetylcysteine
description: N-acetylcysteine 600mg taken orally 3 times daily for 6 days prior to exposure to diesel exhaust for 2 hours. The last supplement was taken the morning of the exposure
arm group label: Diesel exhaust with N-acetylcysteine
intervention type: Other
intervention name: Diesel exhaust
description: A placebo tablet taken 3 times daily for 6 days prior to exposure to diesel exhaust for 2 hours. The last supplement was taken the morning of the exposure
arm group label: Diesel exhaust with N-acetylcysteine
arm group label: Diesel exhaust with placebo
intervention type: Other
intervention name: Filtered air
description: A placebo tablet taken 3 times daily for 6 days prior to exposure to filtered air for 2 hours. The last supplement was taken the morning of the exposure
arm group label: Filtered air with placebo
criteria: 
gender: All
minimum age: 19 Years
maximum age: 49 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Christopher Carlsten, MD MPH
role: Principal Investigator
affiliation: University of British Columbia
facility: 
country: Canada
citation: Braman SS. The global burden of asthma. Chest. 2006 Jul;130(1 Suppl):4S-12S. doi: 10.1378/chest.130.1_suppl.4S.
PMID: 16840363
citation: Atkinson RW, Anderson HR, Sunyer J, Ayres J, Baccini M, Vonk JM, Boumghar A, Forastiere F, Forsberg B, Touloumi G, Schwartz J, Katsouyanni K. Acute effects of particulate air pollution on respiratory admissions: results from APHEA 2 project. Air Pollution and Health: a European Approach. Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1860-6. doi: 10.1164/ajrccm.164.10.2010138.
PMID: 11734437
citation: Janssen NA, Brunekreef B, van Vliet P, Aarts F, Meliefste K, Harssema H, Fischer P. The relationship between air pollution from heavy traffic and allergic sensitization, bronchial hyperresponsiveness, and respiratory symptoms in Dutch schoolchildren. Environ Health Perspect. 2003 Sep;111(12):1512-8. doi: 10.1289/ehp.6243.
PMID: 12948892
citation: Mudway IS, Stenfors N, Duggan ST, Roxborough H, Zielinski H, Marklund SL, Blomberg A, Frew AJ, Sandstrom T, Kelly FJ. An in vitro and in vivo investigation of the effects of diesel exhaust on human airway lining fluid antioxidants. Arch Biochem Biophys. 2004 Mar 1;423(1):200-12. doi: 10.1016/j.abb.2003.12.018.
PMID: 14871482
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: Stenfors N, Nordenhall C, Salvi SS, Mudway I, Soderberg M, Blomberg A, Helleday R, Levin JO, Holgate ST, Kelly FJ, Frew AJ, Sandstrom T. Different airway inflammatory responses in asthmatic and healthy humans exposed to diesel. Eur Respir J. 2004 Jan;23(1):82-6. doi: 10.1183/09031936.03.00004603.
PMID: 14738236
citation: Hashimoto S, Gon Y, Takeshita I, Matsumoto K, Jibiki I, Takizawa H, Kudoh S, Horie T. Diesel exhaust particles activate p38 MAP kinase to produce interleukin 8 and RANTES by human bronchial epithelial cells and N-acetylcysteine attenuates p38 MAP kinase activation. Am J Respir Crit Care Med. 2000 Jan;161(1):280-5. doi: 10.1164/ajrccm.161.1.9904110.
PMID: 10619832
citation: McCreanor J, Cullinan P, Nieuwenhuijsen MJ, Stewart-Evans J, Malliarou E, Jarup L, Harrington R, Svartengren M, Han IK, Ohman-Strickland P, Chung KF, Zhang J. Respiratory effects of exposure to diesel traffic in persons with asthma. N Engl J Med. 2007 Dec 6;357(23):2348-58. doi: 10.1056/NEJMoa071535.
PMID: 18057337
responsible party type: Principal Investigator
investigator affiliation: University of British Columbia
investigator full name: Christopher Carlsten
investigator title: Principal Investigator
mesh term: Asthma
mesh term: Acetylcysteine
mesh term: N-monoacetylcystine