<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/NCT02235714</url>
  </required_header>
  <id_info>
    <org_study_id>RAD-09-031</org_study_id>
    <nct_id>NCT02235714</nct_id>
  </id_info>
  <brief_title>Exhaled Breath Condensate Biomarkers of Inflammation in Individuals With Chronic Cervical Spinal Cord Injury</brief_title>
  <official_title>Exhaled Breath Condensate Biomarkers of Inflammation in Individuals With Chronic Cervical Spinal Cord Injury</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>James J. Peters Veterans Affairs Medical Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>James J. Peters Veterans Affairs Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to obtain markers of airway inflammation from the exhaled breath&#xD;
      condensate (the moisture in exhaled air) for comparison to blood based markers. These markers&#xD;
      will be compared in tetraplegic, asthmatic and able-bodied control groups. Additionally, lung&#xD;
      function testing will be performed, and the associations between breath condensate and blood&#xD;
      markers and pulmonary function explored between groups.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The predominant mechanism for pulmonary dysfunction in individuals with chronic tetraplegia&#xD;
      is respiratory muscle paralysis. This leads to inadequate ventilation and inability to clear&#xD;
      secretions placing these patients at a greater risk for the development of respiratory&#xD;
      complications. Furthermore, individuals with chronic tetraplegia exhibit baseline increases&#xD;
      in airway tone (bronchoconstriction), restoration of normal airway caliber following&#xD;
      bronchodilator administration, and non-specific airway hyperresponsiveness (AHR) following&#xD;
      inhalation of methacholine, histamine, an aerosolized distilled water. These findings in&#xD;
      persons with spinal cord injury (SCI) represent pulmonary features commonly seen in&#xD;
      individuals with asthma. Alternatively, airway inflammation may play a role in the&#xD;
      obstructive physiology observed in individuals with tetraplegia. In this population,&#xD;
      identification of cellular inflammation would confirm the presence of underlying inflammation&#xD;
      with a sputum induction. However, this method is hard to perform due to an impaired cough.&#xD;
&#xD;
      The emerging field of exhaled breath condensate (EBC) biomarkers of inflammation offers a&#xD;
      non-invasive technique to define the presence of, and potentially address the contributing&#xD;
      factors of airway inflammation in the respiratory tract of individuals with tetraplegia. It&#xD;
      is thought that EBC composition reflects biochemical changes of airway lining fluid. EBC&#xD;
      contains a large number of mediators, including adenosine, ammonia, hydrogen peroxide (H2O2),&#xD;
      isoprostanes, leukotrienes, prostanoids, peptides and cytokines. Looking at exhaled breath&#xD;
      profiles of various biomarkers may be used to differentiate their different&#xD;
      pathophysiological mechanism of inflammation. In addition, measurements of some chemokines&#xD;
      (TNF-ά, interleukin (IL)-6) and inflammatory biomarkers (LTB4) in EBC and blood&#xD;
      simultaneously may help differentiate the degree of local vs. systemic inflammation.&#xD;
      Understanding the underlying mechanisms involved in pulmonary dysfunction observed in persons&#xD;
      with chronic cervical SCI may identify treatment options, such as use of inhaled steroids.&#xD;
      This approach would be expected to ultimately improve quality of life in affected&#xD;
      individuals, decreasing the rate of re-hospitalizations due to respiratory complications and&#xD;
      the socioeconomic burden placed on these with SCI and the health care system.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2009</start_date>
  <completion_date type="Actual">April 2012</completion_date>
  <primary_completion_date type="Actual">April 2011</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Levels of inflammatory biomarkers</measure>
    <time_frame>Baseline</time_frame>
    <description>To compare the levels of inflammatory biomarkers in exhaled breath condensate (breath condensate acidity, 8-isoprostane, LTB4, prostaglandin E2, IL-6, TNF-ά in individuals with tetraplegia to that of matched control subjects diagnosed with asthma (positive control) and healthy able-bodied individuals (negative controls).</description>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">36</enrollment>
  <condition>Tetraplegia</condition>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Tetraplegia</arm_group_label>
    <description>Individuals with chronic tetraplegia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Asthma</arm_group_label>
    <description>Individuals with mild asthma</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Able-bodied controls</arm_group_label>
    <description>Age matched able-bodied (AB) controls with no history of lung disease</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Exhaled Breath Condensate Blood Serum&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        1. Chronic stable tetraplegia (duration of injury &gt; 1 year) matched for age, gender, and&#xD;
             BMI with healthy control subjects, and clinically stable mild asthmatic subjects. The&#xD;
             subjects approached will have already consented to, or be actively participating in&#xD;
             &quot;Effects of Nitric Oxide Synthase Inhibitor on Levels of Exhaled NO and Airway Tone in&#xD;
             Subjects with Chronic Cervical Spinal Cord Injury&quot; study.&#xD;
&#xD;
          2. Clinically stable mild asthmatic subjects (as defined by NIH asthma guidelines) [51].&#xD;
&#xD;
          3. Healthy able-bodied individuals.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        (1) 18 to 65 years old.&#xD;
&#xD;
        Groups:&#xD;
&#xD;
          1. Chronic stable tetraplegia (duration of injury &gt; 1 year) matched for age, gender, and&#xD;
             BMI with healthy control subjects, and clinically stable mild asthmatic subjects. The&#xD;
             subjects approached will have already consented to, or be actively participating in&#xD;
             &quot;Effects of Nitric Oxide Synthase Inhibitor on Levels of Exhaled NO and Airway Tone in&#xD;
             Subjects with Chronic Cervical Spinal Cord Injury&quot; study.&#xD;
&#xD;
          2. Clinically stable mild asthmatic subjects (as defined by NIH asthma guidelines) [51].&#xD;
&#xD;
          3. Healthy able-bodied individuals.&#xD;
&#xD;
        Exclusion criteria (all subjects):&#xD;
&#xD;
          1. Smoking, active or history of smoking during life time.&#xD;
&#xD;
          2. More than mild airflow obstruction as per spirometric indices,&#xD;
&#xD;
          3. Active respiratory disease,&#xD;
&#xD;
          4. Medications known to affect the respiratory system,&#xD;
&#xD;
          5. Pregnancy and&#xD;
&#xD;
          6. Lack of mental capacity to give informed consent.&#xD;
&#xD;
          7. No history of asthma diagnosis during lifetime (able bodied and tetraplegia groups),&#xD;
             or recent (within 3 months) respiratory infection for all groups.&#xD;
&#xD;
          8. Receiving medications known to alter airway caliber.&#xD;
&#xD;
        Exclusion Criteria (specific to Asthmatic subjects):&#xD;
&#xD;
          1. Moderate to severe airflow obstruction as per spirometric indices,&#xD;
&#xD;
          2. Testing within 48 hours of last administration of long-acting inhaled bronchodilator&#xD;
             medication,&#xD;
&#xD;
          3. Testing within 7 days of last administration of inhaled or oral corticosteroid&#xD;
             medication,&#xD;
&#xD;
          4. Testing within 24 hours since last administration of leukotriene modifiers and&#xD;
&#xD;
          5. Testing within 8 hours of last administration of a short-acting inhaled bronchodilator&#xD;
             medications&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>89 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Miroslav Radulovic, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>James J. Peters Veterans Affairs Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>James J. Peters VA Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10468</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>December 5, 2012</study_first_submitted>
  <study_first_submitted_qc>September 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2014</study_first_posted>
  <last_update_submitted>September 8, 2014</last_update_submitted>
  <last_update_submitted_qc>September 8, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 10, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>James J. Peters Veterans Affairs Medical Center</investigator_affiliation>
    <investigator_full_name>Miroslav Radulovic, M.D.</investigator_full_name>
    <investigator_title>Staff Physician</investigator_title>
  </responsible_party>
  <keyword>Airway inflammation</keyword>
  <keyword>Tetraplegia</keyword>
  <keyword>Asthma</keyword>
  <keyword>Exhaled breath condensate</keyword>
  <keyword>Spirometry</keyword>
  <keyword>Pulmonary Function Testing</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Cord Injuries</mesh_term>
    <mesh_term>Quadriplegia</mesh_term>
    <mesh_term>Inflammation</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/NCT02235714
org study id: RAD-09-031
nct id: NCT02235714
lead sponsor: 
has dmc: No
The purpose of this study is to obtain markers of airway inflammation from the exhaled breath
      condensate (the moisture in exhaled air) for comparison to blood based markers. These markers
      will be compared in tetraplegic, asthmatic and able-bodied control groups. Additionally, lung
      function testing will be performed, and the associations between breath condensate and blood
      markers and pulmonary function explored between groups.
The predominant mechanism for pulmonary dysfunction in individuals with chronic tetraplegia
      is respiratory muscle paralysis. This leads to inadequate ventilation and inability to clear
      secretions placing these patients at a greater risk for the development of respiratory
      complications. Furthermore, individuals with chronic tetraplegia exhibit baseline increases
      in airway tone (bronchoconstriction), restoration of normal airway caliber following
      bronchodilator administration, and non-specific airway hyperresponsiveness (AHR) following
      inhalation of methacholine, histamine, an aerosolized distilled water. These findings in
      persons with spinal cord injury (SCI) represent pulmonary features commonly seen in
      individuals with asthma. Alternatively, airway inflammation may play a role in the
      obstructive physiology observed in individuals with tetraplegia. In this population,
      identification of cellular inflammation would confirm the presence of underlying inflammation
      with a sputum induction. However, this method is hard to perform due to an impaired cough.

      The emerging field of exhaled breath condensate (EBC) biomarkers of inflammation offers a
      non-invasive technique to define the presence of, and potentially address the contributing
      factors of airway inflammation in the respiratory tract of individuals with tetraplegia. It
      is thought that EBC composition reflects biochemical changes of airway lining fluid. EBC
      contains a large number of mediators, including adenosine, ammonia, hydrogen peroxide (H2O2),
      isoprostanes, leukotrienes, prostanoids, peptides and cytokines. Looking at exhaled breath
      profiles of various biomarkers may be used to differentiate their different
      pathophysiological mechanism of inflammation. In addition, measurements of some chemokines
      (TNF-ά, interleukin (IL)-6) and inflammatory biomarkers (LTB4) in EBC and blood
      simultaneously may help differentiate the degree of local vs. systemic inflammation.
      Understanding the underlying mechanisms involved in pulmonary dysfunction observed in persons
      with chronic cervical SCI may identify treatment options, such as use of inhaled steroids.
      This approach would be expected to ultimately improve quality of life in affected
      individuals, decreasing the rate of re-hospitalizations due to respiratory complications and
      the socioeconomic burden placed on these with SCI and the health care system.
observational model: Case-Control
time perspective: Prospective
measure: Levels of inflammatory biomarkers
time frame: Baseline
description: To compare the levels of inflammatory biomarkers in exhaled breath condensate (breath condensate acidity, 8-isoprostane, LTB4, prostaglandin E2, IL-6, TNF-ά in individuals with tetraplegia to that of matched control subjects diagnosed with asthma (positive control) and healthy able-bodied individuals (negative controls).
arm group label: Tetraplegia
description: Individuals with chronic tetraplegia
arm group label: Asthma
description: Individuals with mild asthma
arm group label: Able-bodied controls
description: Age matched able-bodied (AB) controls with no history of lung disease
Exhaled Breath Condensate Blood Serum
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 89 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Miroslav Radulovic, MD
role: Principal Investigator
affiliation: James J. Peters Veterans Affairs Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: James J. Peters Veterans Affairs Medical Center
investigator full name: Miroslav Radulovic, M.D.
investigator title: Staff Physician
mesh term: Spinal Cord Injuries
mesh term: Quadriplegia
mesh term: Inflammation