<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/NCT03285893</url>
  </required_header>
  <id_info>
    <org_study_id>2017NTLS019</org_study_id>
    <nct_id>NCT03285893</nct_id>
  </id_info>
  <brief_title>Oral Cell DNA Adducts in Smokers</brief_title>
  <acronym>OCDNA</acronym>
  <official_title>Quantitation of Oral Cell DNA Adducts in Smokers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Hawaii</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Minnesota</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      DNA adducts in the oral mucosa cells of 100 smokers from 3 ethnic groups - Native Hawaiians,&#xD;
      Whites, and Japanese Americans with differing risks for lung cancer upon cigarette smoking&#xD;
      will be quantified. DNA adducts of tobacco smoke carcinogens will be quantified using both&#xD;
      targeted and untargeted approaches.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Using high resolution mass spectrometry, quantify known DNA adducts in oral mucosa cells of&#xD;
      100 smokers from each ethnic group - Native Hawaiians, Whites, and Japanese Americans. DNA&#xD;
      adducts of tobacco-specific compounds, formaldehyde, and acrolein will be quantified.&#xD;
&#xD;
      2. Analyze the urine of 100 smokers and 100 non-smokers from each of these groups for&#xD;
      mercapturic acids of acrolein and crotonaldehyde, the F2-isoprostane 8-iso-PGF-2α, a&#xD;
      biomarker of oxidative damage, and the prostaglandin E2 metabolite PGEM, a biomarker of&#xD;
      inflammation, as well as total nicotine equivalents and total NNAL (smokers only). These data&#xD;
      will provide critical information relevant to the high risk of Native Hawaiians for lung&#xD;
      cancer, and in relationship to the DNA adduct measurements of Specific Aim 1.&#xD;
&#xD;
      3. Use newly developed high resolution mass spectrometric, high throughput DNA adductomic&#xD;
      approach to screen for known and unknown DNA adducts to identify a comprehensive DNA&#xD;
      modification signature derived from cigarette smoking.&#xD;
&#xD;
        1. Using a targeted DNA adductomic method, screen for multiple DNA modifications&#xD;
           simultaneously. The adducts analyzed in Specific Aim 1 will be added to a list including&#xD;
           endogenous, 1,3-butadiene-derived (in collaboration with Project 3), aldehyde-derived&#xD;
           and nitrosamine or alkylating agent-derived DNA adducts. In parallel, apply DNA&#xD;
           adductomic methods in an untargeted mode to investigate the presence of previously&#xD;
           unknown DNA adducts. The unknown adducts detected by the untargeted analysis will be&#xD;
           included in the list of targeted DNA adducts to ultimately obtain a sensitive method to&#xD;
           assess overall DNA damage resulting from cigarette smoking.&#xD;
&#xD;
        2. The list of DNA adducts created in Specific Aim 3a will be applied to investigate&#xD;
           differences in the DNA damage signature in selected samples analyzed in Specific Aim 1.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">June 1, 2023</start_date>
  <completion_date type="Anticipated">January 31, 2027</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2026</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Quantitation of oral cell DNA adducts</measure>
    <time_frame>Baseline</time_frame>
    <description>DNA adducts of acrolein, formaldehyde, and tobacco-specific compounds</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Urinary metabolites</measure>
    <time_frame>Baseline</time_frame>
    <description>Metabolites of acrolein crotonaldehyde, oxidative damage and inflammation</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Native Hawaiian cigarette smokers</arm_group_label>
    <description>oral cell DNA adducts</description>
  </arm_group>
  <arm_group>
    <arm_group_label>White (European Americans) cigarette smokers</arm_group_label>
    <description>oral cell DNA adducts</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Japanese American cigarette smokers</arm_group_label>
    <description>oral cell DNA adducts</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>oral cell DNA adducts</intervention_name>
    <description>oral cells will be collected, DNA isolated, and analyzed for adducts</description>
    <arm_group_label>Japanese American cigarette smokers</arm_group_label>
    <arm_group_label>Native Hawaiian cigarette smokers</arm_group_label>
    <arm_group_label>White (European Americans) cigarette smokers</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      oral cell DNA and urine&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        100 each of three ethnic groups: Native Hawaiians, Japanese Americans, whites&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  currently smoke at least 5 cigarettes per day, self-identified Japanese Americans,&#xD;
             European Americans, or Native Hawaiians.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  no current use of other nicotine containing products, no acute or uncontrolled medical&#xD;
             or psychiatric conditions, no greater than 14 alcoholic drinks per week, not pregnant,&#xD;
             not breastfeeding, not currently taking any medications that affect relevant metabolic&#xD;
             enzymes, no active infection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Stepehn Hecht, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Joni Jensen, MPH</last_name>
    <phone>612-624-5178</phone>
    <email>jense010@umn.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Stephen S Hecht, Ph.D</last_name>
    <phone>612-624-7604</phone>
    <email>hecht002@umn.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Tobacco Use Research Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
    <contact>
      <last_name>Joni A Jensen, MPH</last_name>
      <phone>612-624-5178</phone>
      <email>jense010@umn.edu</email>
    </contact>
    <contact_backup>
      <last_name>Stephen S Hecht, Ph.D.</last_name>
      <phone>612-624-7604</phone>
      <email>hecht002@umn.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Stephen S Hecht, Ph.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>September 1, 2017</study_first_submitted>
  <study_first_submitted_qc>September 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 18, 2017</study_first_posted>
  <last_update_submitted>September 29, 2022</last_update_submitted>
  <last_update_submitted_qc>September 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Only unidentified data will be shared.</ipd_description>
  </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/NCT03285893
org study id: 2017NTLS019
nct id: NCT03285893
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
DNA adducts in the oral mucosa cells of 100 smokers from 3 ethnic groups - Native Hawaiians,
      Whites, and Japanese Americans with differing risks for lung cancer upon cigarette smoking
      will be quantified. DNA adducts of tobacco smoke carcinogens will be quantified using both
      targeted and untargeted approaches.
Using high resolution mass spectrometry, quantify known DNA adducts in oral mucosa cells of
      100 smokers from each ethnic group - Native Hawaiians, Whites, and Japanese Americans. DNA
      adducts of tobacco-specific compounds, formaldehyde, and acrolein will be quantified.

      2. Analyze the urine of 100 smokers and 100 non-smokers from each of these groups for
      mercapturic acids of acrolein and crotonaldehyde, the F2-isoprostane 8-iso-PGF-2α, a
      biomarker of oxidative damage, and the prostaglandin E2 metabolite PGEM, a biomarker of
      inflammation, as well as total nicotine equivalents and total NNAL (smokers only). These data
      will provide critical information relevant to the high risk of Native Hawaiians for lung
      cancer, and in relationship to the DNA adduct measurements of Specific Aim 1.

      3. Use newly developed high resolution mass spectrometric, high throughput DNA adductomic
      approach to screen for known and unknown DNA adducts to identify a comprehensive DNA
      modification signature derived from cigarette smoking.

        1. Using a targeted DNA adductomic method, screen for multiple DNA modifications
           simultaneously. The adducts analyzed in Specific Aim 1 will be added to a list including
           endogenous, 1,3-butadiene-derived (in collaboration with Project 3), aldehyde-derived
           and nitrosamine or alkylating agent-derived DNA adducts. In parallel, apply DNA
           adductomic methods in an untargeted mode to investigate the presence of previously
           unknown DNA adducts. The unknown adducts detected by the untargeted analysis will be
           included in the list of targeted DNA adducts to ultimately obtain a sensitive method to
           assess overall DNA damage resulting from cigarette smoking.

        2. The list of DNA adducts created in Specific Aim 3a will be applied to investigate
           differences in the DNA damage signature in selected samples analyzed in Specific Aim 1.
observational model: Cohort
time perspective: Prospective
measure: Quantitation of oral cell DNA adducts
time frame: Baseline
description: DNA adducts of acrolein, formaldehyde, and tobacco-specific compounds
measure: Urinary metabolites
time frame: Baseline
description: Metabolites of acrolein crotonaldehyde, oxidative damage and inflammation
arm group label: Native Hawaiian cigarette smokers
description: oral cell DNA adducts
arm group label: White (European Americans) cigarette smokers
description: oral cell DNA adducts
arm group label: Japanese American cigarette smokers
description: oral cell DNA adducts
intervention type: Other
intervention name: oral cell DNA adducts
description: oral cells will be collected, DNA isolated, and analyzed for adducts
arm group label: Japanese American cigarette smokers
arm group label: Native Hawaiian cigarette smokers
arm group label: White (European Americans) cigarette smokers
oral cell DNA and urine
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
last name: Stepehn Hecht, PhD
role: Principal Investigator
affiliation: University of Minnesota
last name: Joni Jensen, MPH
phone: 612-624-5178
email: jense010@umn.edu
last name: Stephen S Hecht, Ph.D
phone: 612-624-7604
email: hecht002@umn.edu
facility: 
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Sponsor
sharing ipd: Undecided
ipd description: Only unidentified data will be shared.