<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/NCT02183818</url>
  </required_header>
  <id_info>
    <org_study_id>1301013416</org_study_id>
    <secondary_id>R01HL118541</secondary_id>
    <nct_id>NCT02183818</nct_id>
  </id_info>
  <brief_title>Integrative-omics of the Disordered COPD Small Airway Epithelium</brief_title>
  <official_title>Integrative-omics of the Disordered COPD Small Airway Epithelium</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Weill Medical College of Cornell University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      We aim to use an integrated network systems approach to analyze certain existing small airway&#xD;
      epithelium (SAE) omic data sets at the genetic, epigenetic (methylation), gene expression,&#xD;
      microRNA and metabolomic levels, to develop an initial model of network connectivities and&#xD;
      key network pressure points relevant to SAE biology in health and disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hypothesis: We hypothesize that the disordered differentiation of the SAE that characterizes&#xD;
      COPD results from the complex interaction of cigarette smoke components with a hierarchy of&#xD;
      genetic, epigenetic, gene expression and metabolomics network interactions as the BC&#xD;
      differentiate into a mucociliary epithelium.&#xD;
&#xD;
      Specific aim 1. Using an integrated network systems approach to analyze our extensive&#xD;
      existing SAE omic data sets at the genetic, epigenetic (methylation), gene expression,&#xD;
      microRNA and metabolomics levels, to develop an initial model of network connectivities and&#xD;
      key network pressure points relevant to SAE biology in health and disease.&#xD;
&#xD;
      Specific aim 2. To refine the model, a comprehensive omics data set will be collected at&#xD;
      multiple time points as SAE BC of nonsmokers and COPD smokers differentiate to normal and&#xD;
      disordered mucociliary epithelium (respectively) on air-liquid interface (ALI) culture, an in&#xD;
      vitro model of SAE differentiation. The computational strategies from aim 1 will be used to&#xD;
      improve the model with these data.&#xD;
&#xD;
      Specific aim 3. To test and finalize the integrated network model, a parallel omics data set&#xD;
      will be generated from BC from nonsmokers, and COPD smokers as they differentiate on ALI&#xD;
      under conditions where key hubs will be up- or down-regulated and the differentiation process&#xD;
      stressed under conditions mimicking the in vivo SAE environment. The end result will be an&#xD;
      integrated systems model of SAE biology and how this is disordered in COPD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 6, 2015</start_date>
  <completion_date type="Actual">October 15, 2020</completion_date>
  <primary_completion_date type="Actual">November 17, 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>Identification of network pressure points relevant to SAE biology confirmed by analyze of SAE data sets.</measure>
    <time_frame>One Year</time_frame>
    <description>Using an integrated network systems approach to analyze our extensive existing SAE omic data sets at the genetic, epigenetic (methylation), gene expression, microRNA and metabolomics levels, to develop an initial model of network connectivities and key network pressure points relevant to SAE biology in health and disease.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">42</enrollment>
  <condition>Smoking</condition>
  <condition>COPD</condition>
  <arm_group>
    <arm_group_label>Healthy nonsmokers</arm_group_label>
    <description>Physical assessment, EKG, blood and urine draw, chest x-ray, pulmonary function test (PFT), and bronchoscopy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Smokers with COPD</arm_group_label>
    <description>Physical assessment, EKG, blood and urine draw, chest x-ray, pulmonary function test (PFT), and bronchoscopy</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        New York Metropolitan Area residents&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Healthy nonsmokers (n=50)&#xD;
&#xD;
        Inclusion criteria&#xD;
&#xD;
          -  Must be enrolled into IRB approved protocol #1204012331(all inclusion criteria from&#xD;
             protocol #1204012331 thus applies to this protocol)&#xD;
&#xD;
          -  Self-reported never-smokers, with current smoking status validated by the absence of&#xD;
             nicotine metabolites in urine (nicotine less than 2 ng/ml and cotinine less than 5&#xD;
             ng/ml)&#xD;
&#xD;
          -  Negative HIV serology&#xD;
&#xD;
        Smokers with COPD (n=50)&#xD;
&#xD;
        Inclusion criteria&#xD;
&#xD;
          -  Must be enrolled into IRB approved protocol #1204012331(all inclusion criteria from&#xD;
             protocol #1204012331 thus applies to this protocol)&#xD;
&#xD;
          -  Self-reported current daily smokers with greater than or equal to 10 pack-yr,&#xD;
             validated by any of the following: urine nicotine greater than 30 ng/ml or urine&#xD;
             cotinine greater than 50 ng/ml&#xD;
&#xD;
          -  Meeting GOLD stages I-III criteria for chronic obstructive lung disease (COPD) based&#xD;
             on postbronchodilator spirometry&#xD;
&#xD;
          -  Taking any or no pulmonary-related medication, including beta-agonists,&#xD;
             anticholinergics, or inhaled corticosteroids&#xD;
&#xD;
          -  Negative HIV serology&#xD;
&#xD;
        Healthy nonsmokers (n=50)&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  Unable to meet the inclusion criteria (all exclusion criteria from protocol&#xD;
             #1204012331 applies to this protocol)&#xD;
&#xD;
          -  Evidence of malignancy within the past 5 years&#xD;
&#xD;
        Smokers with COPD (n=50)&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  Unable to meet the inclusion criteria (all exclusion criteria from protocol&#xD;
             #1204012331 applies to this protocol)&#xD;
&#xD;
          -  Individuals in whom participation in the study would compromise the normal care and&#xD;
             expected progression of their disease&#xD;
&#xD;
          -  Evidence of malignancy within the past 5 years&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ronald G Crystal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Weill Medical College of Cornell University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Weill Cornell Medical College</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>June 17, 2014</study_first_submitted>
  <study_first_submitted_qc>July 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 8, 2014</study_first_posted>
  <last_update_submitted>May 26, 2021</last_update_submitted>
  <last_update_submitted_qc>May 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Smoking</keyword>
  <keyword>COPD</keyword>
  <keyword>Non-Smokers</keyword>
  <keyword>Smokers</keyword>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02183818
org study id: 1301013416
secondary id: R01HL118541
nct id: NCT02183818
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
We aim to use an integrated network systems approach to analyze certain existing small airway
      epithelium (SAE) omic data sets at the genetic, epigenetic (methylation), gene expression,
      microRNA and metabolomic levels, to develop an initial model of network connectivities and
      key network pressure points relevant to SAE biology in health and disease.
Hypothesis: We hypothesize that the disordered differentiation of the SAE that characterizes
      COPD results from the complex interaction of cigarette smoke components with a hierarchy of
      genetic, epigenetic, gene expression and metabolomics network interactions as the BC
      differentiate into a mucociliary epithelium.

      Specific aim 1. Using an integrated network systems approach to analyze our extensive
      existing SAE omic data sets at the genetic, epigenetic (methylation), gene expression,
      microRNA and metabolomics levels, to develop an initial model of network connectivities and
      key network pressure points relevant to SAE biology in health and disease.

      Specific aim 2. To refine the model, a comprehensive omics data set will be collected at
      multiple time points as SAE BC of nonsmokers and COPD smokers differentiate to normal and
      disordered mucociliary epithelium (respectively) on air-liquid interface (ALI) culture, an in
      vitro model of SAE differentiation. The computational strategies from aim 1 will be used to
      improve the model with these data.

      Specific aim 3. To test and finalize the integrated network model, a parallel omics data set
      will be generated from BC from nonsmokers, and COPD smokers as they differentiate on ALI
      under conditions where key hubs will be up- or down-regulated and the differentiation process
      stressed under conditions mimicking the in vivo SAE environment. The end result will be an
      integrated systems model of SAE biology and how this is disordered in COPD.
observational model: Case-Control
time perspective: Prospective
measure: Identification of network pressure points relevant to SAE biology confirmed by analyze of SAE data sets.
time frame: One Year
description: Using an integrated network systems approach to analyze our extensive existing SAE omic data sets at the genetic, epigenetic (methylation), gene expression, microRNA and metabolomics levels, to develop an initial model of network connectivities and key network pressure points relevant to SAE biology in health and disease.
arm group label: Healthy nonsmokers
description: Physical assessment, EKG, blood and urine draw, chest x-ray, pulmonary function test (PFT), and bronchoscopy
arm group label: Smokers with COPD
description: Physical assessment, EKG, blood and urine draw, chest x-ray, pulmonary function test (PFT), and bronchoscopy
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ronald G Crystal, MD
role: Principal Investigator
affiliation: Weill Medical College of Cornell University
facility: 
country: United States
responsible party type: Sponsor
sharing ipd: Undecided