<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/NCT01710319</url>
  </required_header>
  <id_info>
    <org_study_id>201110275</org_study_id>
    <nct_id>NCT01710319</nct_id>
  </id_info>
  <brief_title>Mechanisms of Immunosurveillance for Lung Cancer</brief_title>
  <acronym>MechLungCa</acronym>
  <official_title>Mechanisms of Immunosurveillance for Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Saint Louis VA Medical Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to investigate the differences in &quot;natural killer (NK)&#xD;
      blood cells, a type of white blood cell that fights infection in the body, among different&#xD;
      types of patients that have lung surgery. The four different groups of patients are:&#xD;
&#xD;
        -  smokers with lung cancer&#xD;
&#xD;
        -  smokers without lung cancer&#xD;
&#xD;
        -  non-smokers with lung cancer&#xD;
&#xD;
        -  non-smokers without lung cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Research has shown that different strains of mice possess varying susceptibility to lung&#xD;
      cancer. C3H and C57BL6 mice are highly resistant to lung cancer, whereas A/J and 129 mice are&#xD;
      very susceptible to lung cancer. Data from our lab shows that the mice have different numbers&#xD;
      of natural killer (NK) cells as well as different characteristics of those cells. C3H and&#xD;
      C57BL6 mice have higher numbers of NK cells as well as higher expression of CD11b, whereas&#xD;
      A/J and 129 mice have lower numbers and lower expression.&#xD;
&#xD;
      These findings justify parallel investigation of NK cells in human populations resistant and&#xD;
      susceptible to lung cancer. Through blood samples, circulating NK cells can be counted and&#xD;
      phenotypically analyzed. Smoking can be used as a factor to establish lung cancer risk.&#xD;
      Additionally, non-smokers suffering from lung cancer provide an opportunity to investigate&#xD;
      whether lung cancer patients have lower abundance of NK cells and lesser expression of CD11b,&#xD;
      independent of the effects of smoking.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      The main goal of this study is to investigate the quantitative and phenotypic differences in&#xD;
      circulating NK cells among human populations. Participants will be classified as heavy&#xD;
      smokers (HS), non-smokers (NS), those suffering from lung cancer (LC), and those free from&#xD;
      lung cancer (NC).&#xD;
&#xD;
      Hypothesis #1: NS/LC participants will have fewer NK cells and lower expression of CD11b&#xD;
      compared to HS/NC and NS/NC participants.&#xD;
&#xD;
      Hypothesis #2: NS/LC participants will have more numerous NK cells and higher expression of&#xD;
      CD11b compared to HS/LC participants.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">July 7, 2016</completion_date>
  <primary_completion_date type="Actual">July 7, 2016</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>Number of NK cells</measure>
    <time_frame>Within 5 minutes of blood arrival to lab, processing begins and blood is frozen. Flow cytometry will be completed 1 to 3 months after blood is frozen. Data presentation in 1 to 2 years.</time_frame>
    <description>The first outcome measure is the determination of the number of NK cells as a percentage of all CD45+cells.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Expression of CD11b</measure>
    <time_frame>Within 5 minutes of blood arrival to the lab, processing begins and blood is frozen. Flow cytometry will be completed 1 to 3 months after blood is frozen. Data presentation in 1 to 2 years.</time_frame>
    <description>Expression of CD11b determined by flow cytometry as compared to control (nonsmoker/no cancer cohort. Flow cytometry will be used to analyze NK-specific markers in the blood samples to determine NK cell abundance and phenotypic expression. The NS/NC cohort will serve as the control for measuring CD11b expression.</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">119</enrollment>
  <condition>Lung Cancer</condition>
  <arm_group>
    <arm_group_label>smoker with lung cancer</arm_group_label>
    <description>patients that smoke greater than 45 pack years or have end organ damage due to cigarette smoking and have lung cancer</description>
  </arm_group>
  <arm_group>
    <arm_group_label>smoker without lung cancer</arm_group_label>
    <description>patients that smoke greater than 45 pack years or have end organ damage due to cigarette smoking and do not have lung cancer</description>
  </arm_group>
  <arm_group>
    <arm_group_label>nonsmoker with lung cancer</arm_group_label>
    <description>patients that have smoked less than 100 cigarettes in their lifetime and have lung cancer</description>
  </arm_group>
  <arm_group>
    <arm_group_label>nonsmoker without lung cancer</arm_group_label>
    <description>patients that have smoked less than 100 cigarettes in their lifetime and do not have lung cancer</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>blood draw</intervention_name>
    <description>a blood specimen will be obtained from each patient in the four groups. An optional blood draw after 30 days of initial blood specimen if indicated.</description>
    <arm_group_label>nonsmoker with lung cancer</arm_group_label>
    <arm_group_label>nonsmoker without lung cancer</arm_group_label>
    <arm_group_label>smoker with lung cancer</arm_group_label>
    <arm_group_label>smoker without lung cancer</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      A blood draw will be obtained from patients in order to complete flow cytometry to analyze&#xD;
      NK-specific markers to determine NK cell abundance and phenotypic expression. Obtain an&#xD;
      optional blood draw on pts at least 30 days from the initial draw if transient confounders&#xD;
      (viral infections or leukemoid reactions-a benign transient post-viral increase in WBCs)&#xD;
      noted that could affect the NK Cell's behavior and interfere with the results.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Participants will be patients that visit the Thoracic Surgery clinic or healthy volunteers.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age equal or greater to 18 years&#xD;
&#xD;
          -  Ability to read and write in English&#xD;
&#xD;
          -  Able to participate in the informed consent process&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known active hepatitis B, hepatitis C, or HIV/AIDs (found in medical record)&#xD;
&#xD;
          -  Chemotherapy or radiation therapy within 3 months of enrollment&#xD;
&#xD;
          -  Type 1 Diabetes Mellitus&#xD;
&#xD;
          -  Rheumatoid arthritis, Lupus, Multiple Sclerosis, or any other autoimmune disease as&#xD;
             deemed necessary for exclusion by the Principal Investigator&#xD;
&#xD;
          -  Previous organ transplant&#xD;
&#xD;
          -  Blood transfusion within 3 months prior to enrollment&#xD;
&#xD;
          -  Any previous cancer, excluding a previous lung cancer&#xD;
&#xD;
          -  Steroid use within 4 weeks of enrollment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexander S Krupnick, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Bach PB, Kattan MW, Thornquist MD, Kris MG, Tate RC, Barnett MJ, Hsieh LJ, Begg CB. Variations in lung cancer risk among smokers. J Natl Cancer Inst. 2003 Mar 19;95(6):470-8. doi: 10.1093/jnci/95.6.470.</citation>
    <PMID>12644540</PMID>
  </reference>
  <reference>
    <citation>Bondy SJ, Victor JC, Diemert LM. Origin and use of the 100 cigarette criterion in tobacco surveys. Tob Control. 2009 Aug;18(4):317-23. doi: 10.1136/tc.2008.027276. Epub 2009 Jun 1.</citation>
    <PMID>19491091</PMID>
  </reference>
  <reference>
    <citation>Murala SS, Gelman AE, Kreisel D, Krupnick AS. Natural killer cells play a critical role in immunosurveillance for murine lung cancer. American Surgical Congress, Proceedings in The Journal of Surgical Research 2011; 165: 292-293.</citation>
  </reference>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>October 11, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 19, 2012</study_first_posted>
  <last_update_submitted>May 4, 2018</last_update_submitted>
  <last_update_submitted_qc>May 4, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 7, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Immunoregulation</keyword>
  <keyword>Natural Killer Cells</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</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/NCT01710319
org study id: 201110275
nct id: NCT01710319
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this research study is to investigate the differences in "natural killer (NK)
      blood cells, a type of white blood cell that fights infection in the body, among different
      types of patients that have lung surgery. The four different groups of patients are:

        -  smokers with lung cancer

        -  smokers without lung cancer

        -  non-smokers with lung cancer

        -  non-smokers without lung cancer.
Research has shown that different strains of mice possess varying susceptibility to lung
      cancer. C3H and C57BL6 mice are highly resistant to lung cancer, whereas A/J and 129 mice are
      very susceptible to lung cancer. Data from our lab shows that the mice have different numbers
      of natural killer (NK) cells as well as different characteristics of those cells. C3H and
      C57BL6 mice have higher numbers of NK cells as well as higher expression of CD11b, whereas
      A/J and 129 mice have lower numbers and lower expression.

      These findings justify parallel investigation of NK cells in human populations resistant and
      susceptible to lung cancer. Through blood samples, circulating NK cells can be counted and
      phenotypically analyzed. Smoking can be used as a factor to establish lung cancer risk.
      Additionally, non-smokers suffering from lung cancer provide an opportunity to investigate
      whether lung cancer patients have lower abundance of NK cells and lesser expression of CD11b,
      independent of the effects of smoking.

      Objective:

      The main goal of this study is to investigate the quantitative and phenotypic differences in
      circulating NK cells among human populations. Participants will be classified as heavy
      smokers (HS), non-smokers (NS), those suffering from lung cancer (LC), and those free from
      lung cancer (NC).

      Hypothesis #1: NS/LC participants will have fewer NK cells and lower expression of CD11b
      compared to HS/NC and NS/NC participants.

      Hypothesis #2: NS/LC participants will have more numerous NK cells and higher expression of
      CD11b compared to HS/LC participants.
observational model: Case-Control
time perspective: Prospective
measure: Number of NK cells
time frame: Within 5 minutes of blood arrival to lab, processing begins and blood is frozen. Flow cytometry will be completed 1 to 3 months after blood is frozen. Data presentation in 1 to 2 years.
description: The first outcome measure is the determination of the number of NK cells as a percentage of all CD45+cells.
measure: Expression of CD11b
time frame: Within 5 minutes of blood arrival to the lab, processing begins and blood is frozen. Flow cytometry will be completed 1 to 3 months after blood is frozen. Data presentation in 1 to 2 years.
description: Expression of CD11b determined by flow cytometry as compared to control (nonsmoker/no cancer cohort. Flow cytometry will be used to analyze NK-specific markers in the blood samples to determine NK cell abundance and phenotypic expression. The NS/NC cohort will serve as the control for measuring CD11b expression.
arm group label: smoker with lung cancer
description: patients that smoke greater than 45 pack years or have end organ damage due to cigarette smoking and have lung cancer
arm group label: smoker without lung cancer
description: patients that smoke greater than 45 pack years or have end organ damage due to cigarette smoking and do not have lung cancer
arm group label: nonsmoker with lung cancer
description: patients that have smoked less than 100 cigarettes in their lifetime and have lung cancer
arm group label: nonsmoker without lung cancer
description: patients that have smoked less than 100 cigarettes in their lifetime and do not have lung cancer
intervention type: Other
intervention name: blood draw
description: a blood specimen will be obtained from each patient in the four groups. An optional blood draw after 30 days of initial blood specimen if indicated.
arm group label: nonsmoker with lung cancer
arm group label: nonsmoker without lung cancer
arm group label: smoker with lung cancer
arm group label: smoker without lung cancer
A blood draw will be obtained from patients in order to complete flow cytometry to analyze
      NK-specific markers to determine NK cell abundance and phenotypic expression. Obtain an
      optional blood draw on pts at least 30 days from the initial draw if transient confounders
      (viral infections or leukemoid reactions-a benign transient post-viral increase in WBCs)
      noted that could affect the NK Cell's behavior and interfere with the results.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Alexander S Krupnick, MD
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
citation: Bach PB, Kattan MW, Thornquist MD, Kris MG, Tate RC, Barnett MJ, Hsieh LJ, Begg CB. Variations in lung cancer risk among smokers. J Natl Cancer Inst. 2003 Mar 19;95(6):470-8. doi: 10.1093/jnci/95.6.470.
PMID: 12644540
citation: Bondy SJ, Victor JC, Diemert LM. Origin and use of the 100 cigarette criterion in tobacco surveys. Tob Control. 2009 Aug;18(4):317-23. doi: 10.1136/tc.2008.027276. Epub 2009 Jun 1.
PMID: 19491091
citation: Murala SS, Gelman AE, Kreisel D, Krupnick AS. Natural killer cells play a critical role in immunosurveillance for murine lung cancer. American Surgical Congress, Proceedings in The Journal of Surgical Research 2011; 165: 292-293.
responsible party type: Sponsor
mesh term: Lung Neoplasms