<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/NCT01661582</url>
  </required_header>
  <id_info>
    <org_study_id>MIDAS</org_study_id>
    <nct_id>NCT01661582</nct_id>
  </id_info>
  <brief_title>Myocardial Ischaemia After Exposure to Diesel Exhaust</brief_title>
  <acronym>MIDAS</acronym>
  <official_title>Myocardial Ischaemia After Exposure to Diesel Exhaust</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Edinburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute for Public Health and the Environment (RIVM)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>British Heart Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Edinburgh</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Exposure to particulate air pollution is associated with increases in cardiovascular&#xD;
      mortality and morbidity. The pathophysiological mechanisms underlying this observation are&#xD;
      emerging, and exposure to particulate air pollution has been shown to result in increases in&#xD;
      blood pressure and arterial tone, impaired vascular function and an increased tendency for&#xD;
      blood to clot as well as an increase in atherosclerotic plaque burden. Recent evidence from&#xD;
      panel studies and controlled exposure studies have suggested an increase in myocardial&#xD;
      ischaemia (a reduction in blood flow to the heart) following exposure. In this study we aim&#xD;
      to investigate directly myocardial (heart) blood flow following exposure to diesel exhaust&#xD;
      (as a model of urban air pollution) using CT/PET myocardial perfusion imaging in male&#xD;
      patients with stable coronary disease and healthy male controls. We hypothesize that&#xD;
      following exposure to dilute diesel exhaust:&#xD;
&#xD;
        1. Myocardial blood flow will be reduced&#xD;
&#xD;
        2. Coronary flow reserve will be impaired&#xD;
&#xD;
        3. The magnitude of impairment will be higher in patients with coronary disease as compared&#xD;
           to healthy controls&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2012</start_date>
  <completion_date type="Anticipated">August 2015</completion_date>
  <primary_completion_date type="Anticipated">February 2015</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Myocardial blood flow and coronary flow reserve measured by CT/PET O-15 imaging</measure>
    <time_frame>Immediately following exposure</time_frame>
    <description>Myocardial blood flow will be measured at rest and at peak adenosine stress using CT/PET O-15 myocardial perfusion imaging immediately following exposure to diesel exhaust and filtered air</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Coronary flow reserve determined using doppler echocardiography</measure>
    <time_frame>1 hour following exposure</time_frame>
    <description>Coronary blood flow will be determined in the left anterior descending coronary artery using doppler echocardiography at rest and at peak adenosine stress 1 hour following exposure to diesel exhaust and filtered air</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ultra-sensitive cardiac troponin-I</measure>
    <time_frame>Before, 2 and 24 hours following exposure</time_frame>
    <description>Blood samples will be obtained for measurement of cardiac troponin-I</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ST segment deviation on continuous 12-lead electrocardiography</measure>
    <time_frame>During and for the 24 hours aftet exposure</time_frame>
    <description>A 12-lead electrocardiogram will be continuously recorded using Holter ECG monitor</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Coronary Heart Disease</condition>
  <arm_group>
    <arm_group_label>Filtered Air Exposure</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will be exposed to filtered air for 1 hour during intermittent exercise in a purpose-built exposure facility</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dilute Diesel Exhaust Exposure</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be exposed to dilute diesel exhaust (~300 mcg/m3) for 1 hour during intermittent exercise in a purpose-built exposure facility</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>CT/PET Myocardial Perfusion Imaging using O-15 water</intervention_name>
    <arm_group_label>Dilute Diesel Exhaust Exposure</arm_group_label>
    <arm_group_label>Filtered Air Exposure</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Coronary blood flow measured by doppler echocardiography</intervention_name>
    <arm_group_label>Dilute Diesel Exhaust Exposure</arm_group_label>
    <arm_group_label>Filtered Air Exposure</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy volunteers will be taking no regular medication, have a normal&#xD;
             electrocardiogram and exercise stress test&#xD;
&#xD;
          -  Patients with a previous history of myocardial infarction or successful coronary&#xD;
             revascularization (PTCA or coronary artery bypass grafting) but without symptoms of&#xD;
             angina pectoris will be recruited&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Healthy volunteers:&#xD;
&#xD;
          -  Regular medication&#xD;
&#xD;
          -  Abnormal 12-lead electrocardiogram&#xD;
&#xD;
          -  Abnormal exercise stress test&#xD;
&#xD;
          -  Patients with coronary disease&#xD;
&#xD;
          -  Acute coronary syndrome within past 3 months&#xD;
&#xD;
          -  Impaired left ventricular function&#xD;
&#xD;
          -  Significant valvular heart disease&#xD;
&#xD;
          -  Left ventricular hypertrophy&#xD;
&#xD;
          -  Resting conduction defect&#xD;
&#xD;
          -  Digoxin use&#xD;
&#xD;
          -  Renal impairment (eGFR &lt;60 mL/min)&#xD;
&#xD;
          -  Hepatic impairment&#xD;
&#xD;
          -  Asthma&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David E Newby, PhD FRCP</last_name>
    <role>Study Chair</role>
    <affiliation>University of Edinburgh</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jeremy P Langrish, MB BCh MRCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Edinburgh</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jeremy P Langrish, MB BCh MRCP</last_name>
    <phone>+441312426428</phone>
    <email>jeremy.langrish@ed.ac.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Edinburgh / NHS Lothian</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH16 4SB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Jeremy P Langrish, MB BCh MRCP</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nicholas L Mills, PhD MRCP</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Anoop Shah, MB BCh MRCP</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Mills NL, Tornqvist H, Gonzalez MC, Vink E, Robinson SD, Soderberg S, Boon NA, Donaldson K, Sandstrom T, Blomberg A, Newby DE. Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease. N Engl J Med. 2007 Sep 13;357(11):1075-82. doi: 10.1056/NEJMoa066314.</citation>
    <PMID>17855668</PMID>
  </reference>
  <verification_date>December 2014</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <last_update_submitted>December 2, 2014</last_update_submitted>
  <last_update_submitted_qc>December 2, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 3, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Air Pollution</keyword>
  <keyword>Myocardial Ischaemia</keyword>
  <keyword>Coronary Blood Flow</keyword>
  <keyword>Diesel Exhaust</keyword>
  <keyword>Troponin</keyword>
  <keyword>Electrocardiography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Coronary Disease</mesh_term>
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_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/NCT01661582
org study id: MIDAS
nct id: NCT01661582
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Exposure to particulate air pollution is associated with increases in cardiovascular
      mortality and morbidity. The pathophysiological mechanisms underlying this observation are
      emerging, and exposure to particulate air pollution has been shown to result in increases in
      blood pressure and arterial tone, impaired vascular function and an increased tendency for
      blood to clot as well as an increase in atherosclerotic plaque burden. Recent evidence from
      panel studies and controlled exposure studies have suggested an increase in myocardial
      ischaemia (a reduction in blood flow to the heart) following exposure. In this study we aim
      to investigate directly myocardial (heart) blood flow following exposure to diesel exhaust
      (as a model of urban air pollution) using CT/PET myocardial perfusion imaging in male
      patients with stable coronary disease and healthy male controls. We hypothesize that
      following exposure to dilute diesel exhaust:

        1. Myocardial blood flow will be reduced

        2. Coronary flow reserve will be impaired

        3. The magnitude of impairment will be higher in patients with coronary disease as compared
           to healthy controls
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Myocardial blood flow and coronary flow reserve measured by CT/PET O-15 imaging
time frame: Immediately following exposure
description: Myocardial blood flow will be measured at rest and at peak adenosine stress using CT/PET O-15 myocardial perfusion imaging immediately following exposure to diesel exhaust and filtered air
measure: Coronary flow reserve determined using doppler echocardiography
time frame: 1 hour following exposure
description: Coronary blood flow will be determined in the left anterior descending coronary artery using doppler echocardiography at rest and at peak adenosine stress 1 hour following exposure to diesel exhaust and filtered air
measure: Ultra-sensitive cardiac troponin-I
time frame: Before, 2 and 24 hours following exposure
description: Blood samples will be obtained for measurement of cardiac troponin-I
measure: ST segment deviation on continuous 12-lead electrocardiography
time frame: During and for the 24 hours aftet exposure
description: A 12-lead electrocardiogram will be continuously recorded using Holter ECG monitor
arm group label: Filtered Air Exposure
arm group type: Placebo Comparator
description: Subjects will be exposed to filtered air for 1 hour during intermittent exercise in a purpose-built exposure facility
arm group label: Dilute Diesel Exhaust Exposure
arm group type: Experimental
description: Subjects will be exposed to dilute diesel exhaust (~300 mcg/m3) for 1 hour during intermittent exercise in a purpose-built exposure facility
intervention type: Other
intervention name: CT/PET Myocardial Perfusion Imaging using O-15 water
arm group label: Dilute Diesel Exhaust Exposure
arm group label: Filtered Air Exposure
intervention type: Other
intervention name: Coronary blood flow measured by doppler echocardiography
arm group label: Dilute Diesel Exhaust Exposure
arm group label: Filtered Air Exposure
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: David E Newby, PhD FRCP
role: Study Chair
affiliation: University of Edinburgh
last name: Jeremy P Langrish, MB BCh MRCP
role: Principal Investigator
affiliation: University of Edinburgh
last name: Jeremy P Langrish, MB BCh MRCP
phone: +441312426428
email: jeremy.langrish@ed.ac.uk
facility: 
status: Recruiting
investigator: 
investigator: 
investigator: 
country: United Kingdom
citation: Mills NL, Tornqvist H, Gonzalez MC, Vink E, Robinson SD, Soderberg S, Boon NA, Donaldson K, Sandstrom T, Blomberg A, Newby DE. Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease. N Engl J Med. 2007 Sep 13;357(11):1075-82. doi: 10.1056/NEJMoa066314.
PMID: 17855668
responsible party type: Sponsor
mesh term: Heart Diseases
mesh term: Coronary Disease
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Ischemia