<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/NCT03272685</url>
  </required_header>
  <id_info>
    <org_study_id>2017NTLS107</org_study_id>
    <nct_id>NCT03272685</nct_id>
  </id_info>
  <brief_title>Impact of Very Low Nicotine Content Cigarettes in a Complex Marketplace</brief_title>
  <official_title>Impact of Very Low Nicotine Content Cigarettes in a Complex Marketplace Part of &quot;Evaluating New Nicotine Standards for Cigarettes&quot;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Wake Forest University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Brown University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Minnesota</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This project will examine the impact of very low nicotine content (VLNC) cigarettes in a&#xD;
      complex tobacco and nicotine product marketplace. We will compare the number of cigarettes&#xD;
      smoked and cigarette-free days in an experimental marketplace that contains VLNC cigarettes&#xD;
      versus normal nicotine content (NNC) cigarettes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This randomized, open label, controlled, multi-site study will simulate a &quot;real world&quot;&#xD;
      tobacco environment by providing participants access to an experimental marketplace where&#xD;
      they will be given vouchers for a specified number of points that can be exchanged for study&#xD;
      cigarettes (varying in nicotine content described below) and non-combusted tobacco/nicotine&#xD;
      products (smokeless tobacco, snus, electronic cigarette, medicinal nicotine replacement) and&#xD;
      at the end of the study can exchange unspent points for money.&#xD;
&#xD;
      Subjects (N=200 in each group) will be randomly assigned to: 1) very low nicotine content&#xD;
      cigarettes (VLNC; 0.4 mg/g) along with non-combusted tobacco/nicotine products or 2) normal&#xD;
      nicotine content cigarettes (NNC; 15.8 mg/g) along with non-combusted tobacco/nicotine&#xD;
      products.&#xD;
&#xD;
      Smokers will undergo an orientation visit for screening and then enter a three phase&#xD;
      experimental trial:&#xD;
&#xD;
        1. Phase 1 - Baseline: Two week baseline assessment period during usual brand cigarette&#xD;
           smoking.&#xD;
&#xD;
        2. Phase 2 - Marketplace Adaptation: Two week period where subjects have access to the&#xD;
           marketplace that provides their preferred usual brand cigarettes and selected&#xD;
           non-combusted tobacco products to allow the subject to adjust to the marketplace prior&#xD;
           to randomization;&#xD;
&#xD;
        3. Phase 3 - Intervention: Randomization to a marketplace with access to either VLNC or NNC&#xD;
           cigarettes plus non-combusted products for a 12 week period.&#xD;
&#xD;
      Biomarker samples are collected at baseline, end of Phase 2 and end of week Phase 3 (week&#xD;
      12).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2018</start_date>
  <completion_date type="Actual">January 10, 2023</completion_date>
  <primary_completion_date type="Actual">September 30, 2022</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>Phase III randomized, open label, multi-center study that will examine the impact of very low nicotine content (VLNC) cigarettes using an experimental marketplace that contains tobacco and nicotine products, simulating a real world environment. There are three phases: Phase 1 is smoking usual brand cigarettes. Phase 2 is access to a marketplace with usual brand cigarettes and other non-combusted nicotine and tobacco products. Phase 3 involves access to a marketplace with study cigarettes and other non-combusted nicotine and tobacco products.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cigarettes Per Day (CPD)</measure>
    <time_frame>7 days prior to end of Phase 2 and the end of Week 12 (12 weeks on study cigarettes)</time_frame>
    <description>The mean cigarettes (study and non-study cigarettes) smoked per day based on 7 days Daily Interactive Voice Response (IVR) data at the end of Phase 3 (experimental marketplace with study cigarettes) compared to Phase 2 (experimental marketplace with usual brand cigarettes).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Smoke-free Days</measure>
    <time_frame>12 weeks on study cigarettes</time_frame>
    <description>Rate of smoke-free days, defined as no cigarettes smoked in the past 24 hours calculated as the proportion of smoke-free days out of the total number of days in Phase 3.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent Change in 2-cyanoethyl-mercapturic Acid (CEMA)</measure>
    <time_frame>12 weeks (Phase 3) on study cigarettes</time_frame>
    <description>Change in CEMA (biomarker for the mercapturic acid acrylonitrile) from end of Phase 2 (experimental marketplace with usual brand cigarettes) to end of Phase 3 (experimental marketplace with study cigarettes).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Study Cigarettes Per Day</measure>
    <time_frame>12 weeks (Phase 3) on study cigarettes</time_frame>
    <description>The mean study cigarettes smoked per day based on 7 days Daily Interactive Voice Response (IVR) data at the end of Phase 3 (experimental marketplace with study cigarettes) compared to Phase 2 (experimental marketplace with usual brand cigarettes).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seven-day Abstinence from Cigarettes</measure>
    <time_frame>7 days</time_frame>
    <description>Total cigarettes per day equal to 0 for all 7 days before the week 12 visit and carbon monoxide (CO) ≤ 6ppm at week 12.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">799</enrollment>
  <condition>Tobacco Smoking</condition>
  <condition>Nicotine Dependence</condition>
  <arm_group>
    <arm_group_label>Very Low Nicotine Content Cigarettes</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Very low nicotine content cigarettes (0.4 mg/g nicotine; 9 mg of tar)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal Nicotine Content Cigarettes</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Normal (Conventional) Nicotine Content (15.8 mg/g nicotine; 9 mg of tar)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Very Low Nicotine Content Cigarettes</intervention_name>
    <description>0.4 mg/g nicotine; 9 mg tar</description>
    <arm_group_label>Very Low Nicotine Content Cigarettes</arm_group_label>
    <other_name>Reduced Nicotine Content Cigarettes</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal Nicotine Content Cigarettes</intervention_name>
    <description>15.8 mg/g nicotine; 9 mg tar</description>
    <arm_group_label>Normal Nicotine Content Cigarettes</arm_group_label>
    <other_name>Conventional Nicotine Content Cigarettes</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female;&#xD;
&#xD;
          2. At least 21 years of age;&#xD;
&#xD;
          3. Biochemically confirmed smoker.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unstable health condition;&#xD;
&#xD;
          2. Unstable medications;&#xD;
&#xD;
        d) Pregnant or nursing.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dorothy Hatsukami, PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tobacco Research Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tobacco Research Programs</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55414</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Center for Addiction Science and Technology</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest Tobacco Control Center of Excellence</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27175</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Interdisciplinary Research on Nicotine Addiction</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brown University Center for Alcohol and Addiction Studies School of Public Health</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 10, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>January 17, 2023</last_update_submitted>
  <last_update_submitted_qc>January 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Reduced nicotine cigarettes</keyword>
  <keyword>Alternative nicotine products</keyword>
  <keyword>Biomarkers of tobacco exposure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tobacco Use Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nicotine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Intend to share findings from this research through publications and presentations. Institutions and individuals wishing to access any resources or data must contact the Principal Investigator (Hatsukami). Data will be available in two formats. One will be a summary of the data, with graphs and tables, posted as pdf files and as raw individual-level data for analysis. Data generated by this grant will be made to outside investigators, according to NIH Guidance. When data are shared, there will be no limits placed on how the data will be used. Users will agree, however, that the recipient must not transfer the data to other users and that the data are only to be used for research purposes. A record of transfer of data and a copy of the dataset that was distributed will be kept by University of Minnesota.</ipd_description>
    <ipd_time_frame>Data will not be available until primary and secondary papers are accepted for publication.</ipd_time_frame>
    <ipd_access_criteria>Persons requesting data must do so in writing, identifying their affiliation and how the data will be used. Upon review, access will be determined.</ipd_access_criteria>
  </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/NCT03272685
org study id: 2017NTLS107
nct id: NCT03272685
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This project will examine the impact of very low nicotine content (VLNC) cigarettes in a
      complex tobacco and nicotine product marketplace. We will compare the number of cigarettes
      smoked and cigarette-free days in an experimental marketplace that contains VLNC cigarettes
      versus normal nicotine content (NNC) cigarettes.
This randomized, open label, controlled, multi-site study will simulate a "real world"
      tobacco environment by providing participants access to an experimental marketplace where
      they will be given vouchers for a specified number of points that can be exchanged for study
      cigarettes (varying in nicotine content described below) and non-combusted tobacco/nicotine
      products (smokeless tobacco, snus, electronic cigarette, medicinal nicotine replacement) and
      at the end of the study can exchange unspent points for money.

      Subjects (N=200 in each group) will be randomly assigned to: 1) very low nicotine content
      cigarettes (VLNC; 0.4 mg/g) along with non-combusted tobacco/nicotine products or 2) normal
      nicotine content cigarettes (NNC; 15.8 mg/g) along with non-combusted tobacco/nicotine
      products.

      Smokers will undergo an orientation visit for screening and then enter a three phase
      experimental trial:

        1. Phase 1 - Baseline: Two week baseline assessment period during usual brand cigarette
           smoking.

        2. Phase 2 - Marketplace Adaptation: Two week period where subjects have access to the
           marketplace that provides their preferred usual brand cigarettes and selected
           non-combusted tobacco products to allow the subject to adjust to the marketplace prior
           to randomization;

        3. Phase 3 - Intervention: Randomization to a marketplace with access to either VLNC or NNC
           cigarettes plus non-combusted products for a 12 week period.

      Biomarker samples are collected at baseline, end of Phase 2 and end of week Phase 3 (week
      12).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Phase III randomized, open label, multi-center study that will examine the impact of very low nicotine content (VLNC) cigarettes using an experimental marketplace that contains tobacco and nicotine products, simulating a real world environment. There are three phases: Phase 1 is smoking usual brand cigarettes. Phase 2 is access to a marketplace with usual brand cigarettes and other non-combusted nicotine and tobacco products. Phase 3 involves access to a marketplace with study cigarettes and other non-combusted nicotine and tobacco products.
primary purpose: Basic Science
masking: None (Open Label)
measure: Cigarettes Per Day (CPD)
time frame: 7 days prior to end of Phase 2 and the end of Week 12 (12 weeks on study cigarettes)
description: The mean cigarettes (study and non-study cigarettes) smoked per day based on 7 days Daily Interactive Voice Response (IVR) data at the end of Phase 3 (experimental marketplace with study cigarettes) compared to Phase 2 (experimental marketplace with usual brand cigarettes).
measure: Smoke-free Days
time frame: 12 weeks on study cigarettes
description: Rate of smoke-free days, defined as no cigarettes smoked in the past 24 hours calculated as the proportion of smoke-free days out of the total number of days in Phase 3.
measure: Percent Change in 2-cyanoethyl-mercapturic Acid (CEMA)
time frame: 12 weeks (Phase 3) on study cigarettes
description: Change in CEMA (biomarker for the mercapturic acid acrylonitrile) from end of Phase 2 (experimental marketplace with usual brand cigarettes) to end of Phase 3 (experimental marketplace with study cigarettes).
measure: Study Cigarettes Per Day
time frame: 12 weeks (Phase 3) on study cigarettes
description: The mean study cigarettes smoked per day based on 7 days Daily Interactive Voice Response (IVR) data at the end of Phase 3 (experimental marketplace with study cigarettes) compared to Phase 2 (experimental marketplace with usual brand cigarettes).
measure: Seven-day Abstinence from Cigarettes
time frame: 7 days
description: Total cigarettes per day equal to 0 for all 7 days before the week 12 visit and carbon monoxide (CO) ≤ 6ppm at week 12.
arm group label: Very Low Nicotine Content Cigarettes
arm group type: Experimental
description: Very low nicotine content cigarettes (0.4 mg/g nicotine; 9 mg of tar)
arm group label: Normal Nicotine Content Cigarettes
arm group type: Active Comparator
description: Normal (Conventional) Nicotine Content (15.8 mg/g nicotine; 9 mg of tar)
intervention type: Drug
intervention name: Very Low Nicotine Content Cigarettes
description: 0.4 mg/g nicotine; 9 mg tar
arm group label: Very Low Nicotine Content Cigarettes
other name: Reduced Nicotine Content Cigarettes
intervention type: Drug
intervention name: Normal Nicotine Content Cigarettes
description: 15.8 mg/g nicotine; 9 mg tar
arm group label: Normal Nicotine Content Cigarettes
other name: Conventional Nicotine Content Cigarettes
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Dorothy Hatsukami, PHD
role: Principal Investigator
affiliation: University of Minnesota
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Tobacco Use Disorder
mesh term: Nicotine
sharing ipd: Yes
ipd description: Intend to share findings from this research through publications and presentations. Institutions and individuals wishing to access any resources or data must contact the Principal Investigator (Hatsukami). Data will be available in two formats. One will be a summary of the data, with graphs and tables, posted as pdf files and as raw individual-level data for analysis. Data generated by this grant will be made to outside investigators, according to NIH Guidance. When data are shared, there will be no limits placed on how the data will be used. Users will agree, however, that the recipient must not transfer the data to other users and that the data are only to be used for research purposes. A record of transfer of data and a copy of the dataset that was distributed will be kept by University of Minnesota.
ipd time frame: Data will not be available until primary and secondary papers are accepted for publication.
ipd access criteria: Persons requesting data must do so in writing, identifying their affiliation and how the data will be used. Upon review, access will be determined.