<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/NCT01733485</url>
  </required_header>
  <id_info>
    <org_study_id>U10HL098177</org_study_id>
    <nct_id>NCT01733485</nct_id>
  </id_info>
  <brief_title>Electrophilic Fatty Acid Derivatives in Asthma</brief_title>
  <acronym>EFADA</acronym>
  <official_title>Electrophilic Fatty Acid Derivatives in Asthma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sally E. Wenzel MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Asthma is an inflammatory disease, which means it causes swelling in the lungs to cause&#xD;
      shortness of breath and/or wheezing. There are several asthma medications that help to reduce&#xD;
      this problem.&#xD;
&#xD;
      The objective of this research study is to characterize the presence of electrophilic fatty&#xD;
      acids in the bronchial airway of subjects with controlled asthma at baseline and after&#xD;
      treatment with Aspirin, Indomethacin, or no treatment at all. The presence of electrophilic&#xD;
      fatty acids may indicate inflammation. Aspirin and Indomethacin are known to respectively&#xD;
      increase and inhibit the formation of electrophilic fatty acids. By gaining a better&#xD;
      understanding of how electrophilic fatty acids work and how they respond to different&#xD;
      treatment, researchers hope to be able to find better ways to lessen airway inflammation in&#xD;
      asthma in the future.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Relevant to asthma, the chemical identities and potent anti-inflammatory signaling actions of&#xD;
      endogenously-produced Electrophilic Fatty acid OXidation products (EFOXs) have recently been&#xD;
      described. Endogenous EFOXs include nitro and alpha and beta-unsaturated ketone derivatives&#xD;
      of unsaturated fatty acids that are generated as byproducts of a) fatty acid oxidation and&#xD;
      nitration by inflammatory-derived reactive species and b) enzymatic fatty acid oxygenation&#xD;
      reactions catalyzed by cyclooxygenase-2 and lipoxygenases. Recent data reveal that multiple&#xD;
      salutary post-translational protein modifications are induced by EFOXs. Specifically, the&#xD;
      covalent adduction of functionally-significant thiols in signaling proteins occurs, with&#xD;
      these reactions modulating critical inflammatory signaling pathways. These signaling proteins&#xD;
      include the nuclear lipid receptor PPARg and the redox-sensitive transcription factors NF&#xD;
      kappaB and Keap1/Nrf2. This proposed research investigates the concept that the reversible&#xD;
      reaction of EFOXs with critical transcription factors results in the regulation of adaptive&#xD;
      responses to inflammation.&#xD;
&#xD;
      In this clinical study, bronchoalveolar lavage fluid (BAL) will be obtained from asthmatics&#xD;
      treated with COX-2 inhibitors that enhance (aspirin) and inhibit (indomethacin) COX-2&#xD;
      dependent EFOX generation, as well as from those assigned to no intervention. BAL will be&#xD;
      obtained from healthy, non-smoking adults with controlled asthma having at least a 12%&#xD;
      increase in FEV1 after short-acting bronchodilator treatment or a positive methacholine&#xD;
      response (reduction in FEV1 ≥ 20% at or before 16 mg/ml). A total of 30 asthmatic subjects&#xD;
      will be randomized (10 per arm) to a) aspirin, b) indomethacin or c) no intervention groups&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2011</start_date>
  <completion_date type="Actual">June 2017</completion_date>
  <primary_completion_date type="Actual">September 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Airway concentration of electrophilic fatty acids</measure>
    <time_frame>Change in the bronchoalveolar lavage concentration of electrophilic fatty acids from the first to the second bronchoscopy</time_frame>
    <description>Patients undergo a baseline bronchoscopy, afterwhich they are randomized to 5 days of a)indomethacin, b) aspirin, c) nothing . After treatment, another bronchoscopy is done. Outcomes are determined after each bronchoscopy</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Asthma</condition>
  <condition>Electrophilic Fatty Acids</condition>
  <arm_group>
    <arm_group_label>Aspirin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Indomethacin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin</intervention_name>
    <description>500 mg/8 h for 5 days</description>
    <arm_group_label>Aspirin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Indomethacin</intervention_name>
    <description>25 mg/8 h for 5 days</description>
    <arm_group_label>Indomethacin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of mild to moderate asthma&#xD;
&#xD;
          -  No evidence of a previous asthma exacerbation in the preceding 6 weeks (defined as&#xD;
             increased severity of respiratory symptoms requiring systemic steroids or escalation&#xD;
             of therapy; b) asthma control questionnaire (ACQ) score less than 1.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of severe asthma, vocal cord dysfunction, cystic fibrosis, COPD, CAD,&#xD;
             hypertension, diabetes or renal failure that is not well controlled&#xD;
&#xD;
          -  Greater than 10 pack-year history of smoking;&#xD;
&#xD;
          -  Stopped smoking less than 1 year prior to study,&#xD;
&#xD;
          -  Taking any aspirin or other NSAIDS on the week prior to bronchoscopy,&#xD;
&#xD;
          -  Taking omega-3 fatty acid supplements&#xD;
&#xD;
          -  If a subject is currently taking an omega-3 fatty acid supplement and is interested in&#xD;
             the study, after a 30 day wash out, the participant can be re-screened and evaluated&#xD;
             for participation.&#xD;
&#xD;
          -  Taking pioglitazone or rosiglitazone (synthetic thiazolidinedione PPARg ligands);&#xD;
&#xD;
          -  other known pulmonary diseases;&#xD;
&#xD;
          -  Inability to undergo bronchoscopy,&#xD;
&#xD;
          -  Contraindications or allergy to aspirin or indomethacin,&#xD;
&#xD;
          -  Asthmatics with known hypersensitivity to aspirin, and&#xD;
&#xD;
          -  Steroid (systemic) dependent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fernando Holguin, MD MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>November 15, 2012</study_first_submitted>
  <study_first_submitted_qc>November 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <last_update_submitted>July 5, 2017</last_update_submitted>
  <last_update_submitted_qc>July 5, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Sally E. Wenzel MD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Asthma</keyword>
  <keyword>Electrophilic Fatty Acids</keyword>
  <keyword>Inflammation</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>Aspirin</mesh_term>
    <mesh_term>Indomethacin</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/NCT01733485
org study id: U10HL098177
nct id: NCT01733485
lead sponsor: 
has dmc: Yes
Asthma is an inflammatory disease, which means it causes swelling in the lungs to cause
      shortness of breath and/or wheezing. There are several asthma medications that help to reduce
      this problem.

      The objective of this research study is to characterize the presence of electrophilic fatty
      acids in the bronchial airway of subjects with controlled asthma at baseline and after
      treatment with Aspirin, Indomethacin, or no treatment at all. The presence of electrophilic
      fatty acids may indicate inflammation. Aspirin and Indomethacin are known to respectively
      increase and inhibit the formation of electrophilic fatty acids. By gaining a better
      understanding of how electrophilic fatty acids work and how they respond to different
      treatment, researchers hope to be able to find better ways to lessen airway inflammation in
      asthma in the future.
Relevant to asthma, the chemical identities and potent anti-inflammatory signaling actions of
      endogenously-produced Electrophilic Fatty acid OXidation products (EFOXs) have recently been
      described. Endogenous EFOXs include nitro and alpha and beta-unsaturated ketone derivatives
      of unsaturated fatty acids that are generated as byproducts of a) fatty acid oxidation and
      nitration by inflammatory-derived reactive species and b) enzymatic fatty acid oxygenation
      reactions catalyzed by cyclooxygenase-2 and lipoxygenases. Recent data reveal that multiple
      salutary post-translational protein modifications are induced by EFOXs. Specifically, the
      covalent adduction of functionally-significant thiols in signaling proteins occurs, with
      these reactions modulating critical inflammatory signaling pathways. These signaling proteins
      include the nuclear lipid receptor PPARg and the redox-sensitive transcription factors NF
      kappaB and Keap1/Nrf2. This proposed research investigates the concept that the reversible
      reaction of EFOXs with critical transcription factors results in the regulation of adaptive
      responses to inflammation.

      In this clinical study, bronchoalveolar lavage fluid (BAL) will be obtained from asthmatics
      treated with COX-2 inhibitors that enhance (aspirin) and inhibit (indomethacin) COX-2
      dependent EFOX generation, as well as from those assigned to no intervention. BAL will be
      obtained from healthy, non-smoking adults with controlled asthma having at least a 12%
      increase in FEV1 after short-acting bronchodilator treatment or a positive methacholine
      response (reduction in FEV1 ≥ 20% at or before 16 mg/ml). A total of 30 asthmatic subjects
      will be randomized (10 per arm) to a) aspirin, b) indomethacin or c) no intervention groups
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Airway concentration of electrophilic fatty acids
time frame: Change in the bronchoalveolar lavage concentration of electrophilic fatty acids from the first to the second bronchoscopy
description: Patients undergo a baseline bronchoscopy, afterwhich they are randomized to 5 days of a)indomethacin, b) aspirin, c) nothing . After treatment, another bronchoscopy is done. Outcomes are determined after each bronchoscopy
arm group label: Aspirin
arm group type: Active Comparator
arm group label: Indomethacin
arm group type: Active Comparator
arm group label: Control
arm group type: No Intervention
intervention type: Drug
intervention name: Aspirin
description: 500 mg/8 h for 5 days
arm group label: Aspirin
intervention type: Drug
intervention name: Indomethacin
description: 25 mg/8 h for 5 days
arm group label: Indomethacin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Fernando Holguin, MD MPH
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Sally E. Wenzel MD
investigator title: Professor
mesh term: Asthma
mesh term: Aspirin
mesh term: Indomethacin