<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/NCT02250664</url>
  </required_header>
  <id_info>
    <org_study_id>P50DA036114:P2S2</org_study_id>
    <secondary_id>P50DA036114</secondary_id>
    <nct_id>NCT02250664</nct_id>
  </id_info>
  <brief_title>Project 2, Study 2: Extended Exposure to Low Nicotine Content Cigarettes in Opioid Abusers</brief_title>
  <acronym>P2S2</acronym>
  <official_title>Project 2, Study 2: Extended Exposure to Low Nicotine Content Cigarettes in Opioid Abusers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Vermont</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Vermont</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will examine extended exposure to cigarettes varying in nicotine content among&#xD;
      adults with opioid use disorder. Those with opioid use disorder are at increased risk for&#xD;
      smoking, nicotine dependence, and using high nicotine yield cigarettes and are also at&#xD;
      significantly increased risk for smoking-related adverse health consequences, including site&#xD;
      specific cancers, heart disease, and premature death. Studies testing an innovative&#xD;
      regulatory strategy of reducing the nicotine content of cigarettes to a non-addictive level&#xD;
      have shown promising beneficial effects (decreased smoking rate, reduced toxicant exposure,&#xD;
      and increased cessation) in the general population of smokers. However, these studies have&#xD;
      uniformly excluded vulnerable populations like those with opioid use disorder who may respond&#xD;
      differently considering their greater vulnerability to smoking and nicotine dependence. Thus,&#xD;
      little is known scientifically about how this highly vulnerable subgroup of smokers might&#xD;
      respond to a nicotine reduction policy. This project is designed to address that substantial&#xD;
      knowledge gap. This same study was also conducted in two additional vulnerable populations&#xD;
      under a similar protocol.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary overall objective of these studies is to evaluate the effects of extended&#xD;
      exposure to cigarettes differing in nicotine content in adults with opioid use disorder using&#xD;
      a 3-condition, parallel groups design. After a baseline period in which daily smoking rate&#xD;
      and other baseline assessments are completed, participants will be randomly assigned to one&#xD;
      of three cigarette conditions (nicotine content: 0.04, 2.4, and 15.8 mg nicotine/gram of&#xD;
      tobacco) for the 12-week experimental period.&#xD;
&#xD;
      The cigarettes to be used in this study were made under an NIH contract with production being&#xD;
      overseen by the Research Triangle Institute (referred to as &quot;Spectrum cigarettes&quot;). NIH&#xD;
      currently has approximately 10 million of these cigarettes (of varying types) for research&#xD;
      purposes. The cigarettes selected for the study span the range of yields likely to produce&#xD;
      the hypothesized effects, as described above. The Spectrum cigarettes are not currently&#xD;
      commercially available, although they are similar in many ways to marketed cigarettes (e.g.,&#xD;
      similar manufacturing, filter, paper, etc.).&#xD;
&#xD;
      The primary overall objective of this study is to evaluate the effects of extended exposure&#xD;
      to cigarettes differing in nicotine content in male and female adults with opioid use&#xD;
      disorder using a 3-condition, parallel groups design. After a baseline period in which daily&#xD;
      smoking rate and other baseline assessments are completed, participants will be randomly&#xD;
      assigned to one of three cigarette conditions (nicotine content: 0.04 mg, 2.4 mg, and 15.8 mg&#xD;
      nicotine/g of tobacco) for the 12-week experimental period.&#xD;
&#xD;
      Participants will be seen weekly throughout the 12-week experimental period to obtain&#xD;
      research cigarettes. Cigarettes smoked per day will be obtained by participants completing&#xD;
      daily Interactive Voice Response (IVR) reports of cigarettes in past 24 hours. This daily&#xD;
      data will be used to calculate weekly means, with week-12 means serving as the primary&#xD;
      outcome.&#xD;
&#xD;
      This same study was conducted in two additional vulnerable populations under a similar&#xD;
      protocol, with differences between protocols consisting of data collection specific to that&#xD;
      vulnerable population. This included information such as additional assessments of anxiety&#xD;
      and depression for individuals with affective disorders or other measures specific to&#xD;
      disadvantaged women of reproductive age. In order to explore potential differences across&#xD;
      individuals with different vulnerabilities, data from all three studies were combined for&#xD;
      analysis. A vulnerable population-by-condition or population-by-condition-by-time interaction&#xD;
      term was included in all analyses. In the event that these interaction terms were&#xD;
      statistically significant, all pairwise comparisons were conducted using a Bonferroni&#xD;
      multiple comparison adjustment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2016</start_date>
  <completion_date type="Actual">October 2019</completion_date>
  <primary_completion_date type="Actual">October 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</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>This study was one of three multi-site clinical trials conducted in three different vulnerable populations under a similar protocol, with differences between protocols consisting of data collection specific to that vulnerable population. This included information such as use and timing of opioid maintenance therapy for individuals with opioid-use disorder or additional assessments of anxiety and depression for individuals with affective disorders. In order to explore potential differences across individuals with different vulnerabilities, data from all three studies were combined for analysis. A vulnerable population-by-condition or population-by- condition-by-time interaction term was included in all analyses. In the event that these interaction terms were statistically significant, all pairwise comparisons were conducted using a Bonferroni multiple comparison adjustment. Please see Statistical Analysis Plan for more details.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cigarettes Per Day (CPD)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Participant reported number of cigarettes smoked per day at Week 12</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">775</enrollment>
  <condition>Tobacco Use Disorder</condition>
  <arm_group>
    <arm_group_label>0.8 mg nicotine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.8 mg nicotine very low nicotine content cigarettes</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.12 mg nicotine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.12 mg nicotine very low nicotine content cigarettes</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.03 mg nicotine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.03 mg nicotine very low nicotine content cigarettes</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Very low nicotine content cigarettes</intervention_name>
    <description>Very low nicotine content cigarettes</description>
    <arm_group_label>0.03 mg nicotine</arm_group_label>
    <arm_group_label>0.12 mg nicotine</arm_group_label>
    <arm_group_label>0.8 mg nicotine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men and women ages 18-70, who are currently receiving methadone or buprenorphine&#xD;
             maintenance treatment for opioid dependence.&#xD;
&#xD;
          2. Report smoking ≥ 5 cigarettes per day.&#xD;
&#xD;
          3. Provide an intake breath carbon monoxide (CO) sample &gt;8 ppm.&#xD;
&#xD;
          4. Be without current (within the past year) serious mental disorder that would interfere&#xD;
             with study results or completion as determined by the licensed medical professional or&#xD;
             PI.&#xD;
&#xD;
          5. Be sufficiently literate to complete the research-related tasks.&#xD;
&#xD;
          6. Be in good physical health without serious illness or change in health or medication&#xD;
             (not including methadone or buprenorphine dose) in the past three months as determined&#xD;
             by the license medical professional at each site.&#xD;
&#xD;
          7. Not pregnant or nursing, and report using oral, implant, injection or barrier&#xD;
             contraceptives, or report being surgically sterile, or post menopausal.&#xD;
&#xD;
          8. Report no significant use of other tobacco or nicotine products within the past month&#xD;
             (more than 9 days in the past 30).&#xD;
&#xD;
          9. Participants must be maintained on a stable methadone or buprenorphine dose for the&#xD;
             past month, with no evidence of regular illicit-drug abuse (&lt;30% positive specimens in&#xD;
             the past 30 days).&#xD;
&#xD;
               1. Consent to confirm dose and drug abstinence with the participant's opioid clinic&#xD;
                  will be obtained at screening and we will monitor any changes in dose throughout&#xD;
                  the study.&#xD;
&#xD;
               2. Participants must provide at least three urine samples within the last 30 days.&#xD;
                  If they do not have three they will be asked to come in and provide a sample.&#xD;
                  They may leave up to two samples per week with at least one full day between&#xD;
                  samples.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any prior regular use (used as primary cigarette outside of laboratory) of Spectrum&#xD;
             cigarettes (i.e., research cigarettes with reduced nicotine content).&#xD;
&#xD;
          2. Exclusive use of roll-your-own cigarettes.&#xD;
&#xD;
          3. Planning to quit smoking in the next 30 days.&#xD;
&#xD;
          4. A quit attempt in the past 30 days resulting in greater than 3 days of abstinence.&#xD;
&#xD;
          5. Currently taking anticonvulsant medications.&#xD;
&#xD;
          6. Positive toxicology screen for illicit drugs not including Marijuana ( participants&#xD;
             with valid prescriptions will not be excluded and participants with a positive&#xD;
             toxicology screen will be allowed to re-screen once).&#xD;
&#xD;
          7. Not currently enrolled in a treatment program for opioid dependence and/or not&#xD;
             currently stable on their methadone or buprenorphine dose.&#xD;
&#xD;
          8. Breath alcohol level &gt; 0.01 ( participants with a positive screen will be allowed to&#xD;
             re-screen once).&#xD;
&#xD;
          9. Self-report of binge drinking alcohol (more than 9 days in the past 30 days, 4/5&#xD;
             drinks in a 2 hour period in females/males),&#xD;
&#xD;
         10. Blood pressure is greater than or equal to 160/100 mmHg or below 90/50 mmHg&#xD;
             (participants outside the range will be allowed to re-screen once).&#xD;
&#xD;
             a. Participants failing for blood pressure will be allowed to re-screen once.&#xD;
&#xD;
         11. Breath CO &gt; 80 ppm.&#xD;
&#xD;
         12. Heart rate is greater than or equal to 115 bpm or less than 45 bpm ( participants&#xD;
             outside the range will be allowed to re-screen once).&#xD;
&#xD;
         13. Currently seeking treatment for smoking cessation.&#xD;
&#xD;
         14. Have used nicotine replacement, bupropion or other pharmacotherapies as cessation aids&#xD;
             in the past month (bupropion will be allowed for treatment of depression).&#xD;
&#xD;
         15. Current symptoms of psychosis or dementia, or mania.&#xD;
&#xD;
         16. Suicidal ideation in the past month. 17.) Suicide attempt in the past 6 months. 18.)&#xD;
             Participation in another research study in the past 30 days.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephen T. Higgins, Ph.D.</last_name>
    <role>Study Director</role>
    <affiliation>University of Vermont</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Stacey Sigmon, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Vermont</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Vermont</name>
      <address>
        <city>Burlington</city>
        <state>Vermont</state>
        <zip>05401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>September 23, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2014</study_first_posted>
  <results_first_submitted>October 11, 2022</results_first_submitted>
  <results_first_submitted_qc>November 15, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">December 1, 2022</results_first_posted>
  <last_update_submitted>November 15, 2022</last_update_submitted>
  <last_update_submitted_qc>November 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Vermont</investigator_affiliation>
    <investigator_full_name>Stephen T. Higgins, PhD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Biomarkers of exposure</keyword>
  <keyword>Compensatory smoking</keyword>
  <keyword>Nicotine dependence</keyword>
  <keyword>Reduced nicotine cigarettes</keyword>
  <keyword>Tobacco withdrawal</keyword>
  <keyword>Women</keyword>
  <keyword>Health disparities</keyword>
  <keyword>Vulnerable populations</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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 9, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/64/NCT02250664/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>0.8 mg Nicotine</title>
          <description>0.8 mg nicotine very low nicotine content cigarettes&#xD;
Very low nicotine content cigarettes: Very low nicotine content cigarettes</description>
        </group>
        <group group_id="P2">
          <title>0.12 mg Nicotine</title>
          <description>0.12 mg nicotine very low nicotine content cigarettes&#xD;
Very low nicotine content cigarettes: Very low nicotine content cigarettes</description>
        </group>
        <group group_id="P3">
          <title>0.03 mg Nicotine</title>
          <description>0.03 mg nicotine very low nicotine content cigarettes&#xD;
Very low nicotine content cigarettes: Very low nicotine content cigarettes</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="254"/>
                <participants group_id="P2" count="235"/>
                <participants group_id="P3" count="286"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="218"/>
                <participants group_id="P2" count="190"/>
                <participants group_id="P3" count="224"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="45"/>
                <participants group_id="P3" count="62"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="28"/>
                <participants group_id="P3" count="33"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Personal Reasons</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="14"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Incarcerated</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Reason unknown</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>0.8 mg Nicotine</title>
          <description>0.8 mg nicotine very low nicotine content cigarettes&#xD;
Very low nicotine content cigarettes: Very low nicotine content cigarettes</description>
        </group>
        <group group_id="B2">
          <title>0.12 mg Nicotine</title>
          <description>0.12 mg nicotine very low nicotine content cigarettes&#xD;
Very low nicotine content cigarettes: Very low nicotine content cigarettes</description>
        </group>
        <group group_id="B3">
          <title>0.03 mg Nicotine</title>
          <description>0.03 mg nicotine very low nicotine content cigarettes&#xD;
Very low nicotine content cigarettes: Very low nicotine content cigarettes</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="254"/>
            <count group_id="B2" value="235"/>
            <count group_id="B3" value="286"/>
            <count group_id="B4" value="775"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35.90" spread="10.82"/>
                    <measurement group_id="B2" value="35.18" spread="11.13"/>
                    <measurement group_id="B3" value="35.65" spread="11.21"/>
                    <measurement group_id="B4" value="35.59" spread="11.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="184"/>
                    <measurement group_id="B2" value="167"/>
                    <measurement group_id="B3" value="200"/>
                    <measurement group_id="B4" value="551"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                    <measurement group_id="B2" value="68"/>
                    <measurement group_id="B3" value="86"/>
                    <measurement group_id="B4" value="224"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Non-Latino White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="207"/>
                    <measurement group_id="B2" value="183"/>
                    <measurement group_id="B3" value="240"/>
                    <measurement group_id="B4" value="630"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-Latino Black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-Latino Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="254"/>
                    <measurement group_id="B2" value="235"/>
                    <measurement group_id="B3" value="286"/>
                    <measurement group_id="B4" value="775"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cigarettes Per Day</title>
          <units>Cigarettes Per Day</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19.63" spread="10.33"/>
                    <measurement group_id="B2" value="19.54" spread="10.56"/>
                    <measurement group_id="B3" value="19.91" spread="10.84"/>
                    <measurement group_id="B4" value="19.71" spread="10.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Cigarettes Per Day (CPD)</title>
        <description>Participant reported number of cigarettes smoked per day at Week 12</description>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.8 mg Nicotine</title>
            <description>0.8 mg nicotine very low nicotine content cigarettes&#xD;
Very low nicotine content cigarettes: Very low nicotine content cigarettes</description>
          </group>
          <group group_id="O2">
            <title>0.12 mg Nicotine</title>
            <description>0.12 mg nicotine very low nicotine content cigarettes&#xD;
Very low nicotine content cigarettes: Very low nicotine content cigarettes</description>
          </group>
          <group group_id="O3">
            <title>0.03 mg Nicotine</title>
            <description>0.03 mg nicotine very low nicotine content cigarettes&#xD;
Very low nicotine content cigarettes: Very low nicotine content cigarettes</description>
          </group>
        </group_list>
        <measure>
          <title>Cigarettes Per Day (CPD)</title>
          <description>Participant reported number of cigarettes smoked per day at Week 12</description>
          <units>cigarettes per day</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="218"/>
                <count group_id="O2" value="190"/>
                <count group_id="O3" value="224"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.28" spread="0.77"/>
                    <measurement group_id="O2" value="19.95" spread="0.80"/>
                    <measurement group_id="O3" value="17.74" spread="0.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The statistical analysis method was ANCOVA, in order to test for statistically significant differences between group means, while controlling for covariates of interest. It was calculated that 207 subjects per group would be required to have at least 90% power to detect a mean difference of 4.52 CPD between the 0.8 mg and 0.12 mg groups at week 12, with significance level alpha of 0.0167. The significance level reflects the Bonferroni correction needed for testing of all pairwise comparisons.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>The p-value is Bonferroni-corrected for multiple comparisons with a priori threshold of significance P &lt; 0.0167</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-5.33</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.06</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.41</ci_lower_limit>
            <ci_upper_limit>-3.26</ci_upper_limit>
            <estimate_desc>Group difference = 0.12 mg nicotine - 0.8 mg nicotine</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The statistical analysis method was ANCOVA, in order to test for statistically significant differences between group means, while controlling for covariates of interest. It was calculated that 207 subjects per group would be required to have at least 90% power to detect a mean difference of 4.52 CPD between the 0.8 mg and 0.12 mg groups at week 12, with significance level alpha of 0.0167. The significance level reflects the Bonferroni correction needed for testing of all pairwise comparisons.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>The p-value is Bonferroni-corrected for multiple comparisons with a priori threshold of significance P &lt; 0.0167</p_value_desc>
            <method>ANOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-7.54</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.00</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-9.51</ci_lower_limit>
            <ci_upper_limit>-5.57</ci_upper_limit>
            <other_analysis_desc>Group difference = 0.03 mg nicotine - 0.8 mg nicotine</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>0.8 mg Nicotine</title>
          <description>0.8 mg nicotine very low nicotine content cigarettes&#xD;
Very low nicotine content cigarettes: Very low nicotine content cigarettes</description>
        </group>
        <group group_id="E2">
          <title>0.12 mg Nicotine</title>
          <description>0.12 mg nicotine very low nicotine content cigarettes&#xD;
Very low nicotine content cigarettes: Very low nicotine content cigarettes</description>
        </group>
        <group group_id="E3">
          <title>0.03 mg Nicotine</title>
          <description>0.03 mg nicotine very low nicotine content cigarettes&#xD;
Very low nicotine content cigarettes: Very low nicotine content cigarettes</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (5.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="235"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="286"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="254"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="235"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sudden onset of chest pain due to not enough blood going to the heart</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="254"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="235"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="254"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="235"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal disorders</sub_title>
                <description>Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms cannot be separated</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="235"/>
                <counts group_id="E3" events="4" subjects_affected="1" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations</sub_title>
                <description>Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms cannot be separated</description>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="254"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="235"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injury, poisoning and procedural complications</sub_title>
                <description>Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms cannot be separated</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="235"/>
                <counts group_id="E3" events="7" subjects_affected="2" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Investigations</sub_title>
                <description>Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms cannot be separated</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="235"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Metabolism and nutrition disorders</sub_title>
                <description>Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms cannot be separated</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="254"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="235"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Tenosynovitis of the Hand</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="254"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="235"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nervous system disorders</sub_title>
                <description>Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms cannot be separated</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="235"/>
                <counts group_id="E3" events="5" subjects_affected="3" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Psychiatric disorders</sub_title>
                <description>Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms cannot be separated</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="254"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="235"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute renal failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="254"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="235"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin graft to wound on leg</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="254"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="235"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and medical procedures</sub_title>
                <description>Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms cannot be separated</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="254"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="235"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>High blood pressure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="254"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="235"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (5.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="241" subjects_at_risk="254"/>
                <counts group_id="E2" subjects_affected="203" subjects_at_risk="235"/>
                <counts group_id="E3" subjects_affected="226" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal disorders</sub_title>
                <counts group_id="E1" events="92" subjects_affected="63" subjects_at_risk="254"/>
                <counts group_id="E2" events="71" subjects_affected="49" subjects_at_risk="235"/>
                <counts group_id="E3" events="114" subjects_affected="77" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>General disorders</sub_title>
                <counts group_id="E1" events="77" subjects_affected="58" subjects_at_risk="254"/>
                <counts group_id="E2" events="72" subjects_affected="46" subjects_at_risk="235"/>
                <counts group_id="E3" events="85" subjects_affected="67" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations</sub_title>
                <counts group_id="E1" events="113" subjects_affected="89" subjects_at_risk="254"/>
                <counts group_id="E2" events="106" subjects_affected="79" subjects_at_risk="235"/>
                <counts group_id="E3" events="119" subjects_affected="92" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injury, poisoning, and procedural complications</sub_title>
                <counts group_id="E1" events="28" subjects_affected="22" subjects_at_risk="254"/>
                <counts group_id="E2" events="13" subjects_affected="13" subjects_at_risk="235"/>
                <counts group_id="E3" events="23" subjects_affected="17" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorders</sub_title>
                <counts group_id="E1" events="52" subjects_affected="42" subjects_at_risk="254"/>
                <counts group_id="E2" events="34" subjects_affected="27" subjects_at_risk="235"/>
                <counts group_id="E3" events="41" subjects_affected="33" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nervous system disorders</sub_title>
                <counts group_id="E1" events="56" subjects_affected="49" subjects_at_risk="254"/>
                <counts group_id="E2" events="52" subjects_affected="38" subjects_at_risk="235"/>
                <counts group_id="E3" events="65" subjects_affected="46" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory, thoracic, and mediastinal disorders</sub_title>
                <counts group_id="E1" events="112" subjects_affected="78" subjects_at_risk="254"/>
                <counts group_id="E2" events="111" subjects_affected="72" subjects_at_risk="235"/>
                <counts group_id="E3" events="114" subjects_affected="84" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and medical procedures</sub_title>
                <counts group_id="E1" events="28" subjects_affected="23" subjects_at_risk="254"/>
                <counts group_id="E2" events="25" subjects_affected="16" subjects_at_risk="235"/>
                <counts group_id="E3" events="31" subjects_affected="26" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Vascular disorders</sub_title>
                <counts group_id="E1" events="30" subjects_affected="20" subjects_at_risk="254"/>
                <counts group_id="E2" events="31" subjects_affected="22" subjects_at_risk="235"/>
                <counts group_id="E3" events="34" subjects_affected="25" subjects_at_risk="286"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Stephen T. Higgins, PhD, Professor</name_or_title>
      <organization>University of Vermont</organization>
      <phone>802-735-6267</phone>
      <email>stephen.higgins@uvm.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02250664
org study id: P50DA036114:P2S2
secondary id: P50DA036114
nct id: NCT02250664
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This study will examine extended exposure to cigarettes varying in nicotine content among
      adults with opioid use disorder. Those with opioid use disorder are at increased risk for
      smoking, nicotine dependence, and using high nicotine yield cigarettes and are also at
      significantly increased risk for smoking-related adverse health consequences, including site
      specific cancers, heart disease, and premature death. Studies testing an innovative
      regulatory strategy of reducing the nicotine content of cigarettes to a non-addictive level
      have shown promising beneficial effects (decreased smoking rate, reduced toxicant exposure,
      and increased cessation) in the general population of smokers. However, these studies have
      uniformly excluded vulnerable populations like those with opioid use disorder who may respond
      differently considering their greater vulnerability to smoking and nicotine dependence. Thus,
      little is known scientifically about how this highly vulnerable subgroup of smokers might
      respond to a nicotine reduction policy. This project is designed to address that substantial
      knowledge gap. This same study was also conducted in two additional vulnerable populations
      under a similar protocol.
The primary overall objective of these studies is to evaluate the effects of extended
      exposure to cigarettes differing in nicotine content in adults with opioid use disorder using
      a 3-condition, parallel groups design. After a baseline period in which daily smoking rate
      and other baseline assessments are completed, participants will be randomly assigned to one
      of three cigarette conditions (nicotine content: 0.04, 2.4, and 15.8 mg nicotine/gram of
      tobacco) for the 12-week experimental period.

      The cigarettes to be used in this study were made under an NIH contract with production being
      overseen by the Research Triangle Institute (referred to as "Spectrum cigarettes"). NIH
      currently has approximately 10 million of these cigarettes (of varying types) for research
      purposes. The cigarettes selected for the study span the range of yields likely to produce
      the hypothesized effects, as described above. The Spectrum cigarettes are not currently
      commercially available, although they are similar in many ways to marketed cigarettes (e.g.,
      similar manufacturing, filter, paper, etc.).

      The primary overall objective of this study is to evaluate the effects of extended exposure
      to cigarettes differing in nicotine content in male and female adults with opioid use
      disorder using a 3-condition, parallel groups design. After a baseline period in which daily
      smoking rate and other baseline assessments are completed, participants will be randomly
      assigned to one of three cigarette conditions (nicotine content: 0.04 mg, 2.4 mg, and 15.8 mg
      nicotine/g of tobacco) for the 12-week experimental period.

      Participants will be seen weekly throughout the 12-week experimental period to obtain
      research cigarettes. Cigarettes smoked per day will be obtained by participants completing
      daily Interactive Voice Response (IVR) reports of cigarettes in past 24 hours. This daily
      data will be used to calculate weekly means, with week-12 means serving as the primary
      outcome.

      This same study was conducted in two additional vulnerable populations under a similar
      protocol, with differences between protocols consisting of data collection specific to that
      vulnerable population. This included information such as additional assessments of anxiety
      and depression for individuals with affective disorders or other measures specific to
      disadvantaged women of reproductive age. In order to explore potential differences across
      individuals with different vulnerabilities, data from all three studies were combined for
      analysis. A vulnerable population-by-condition or population-by-condition-by-time interaction
      term was included in all analyses. In the event that these interaction terms were
      statistically significant, all pairwise comparisons were conducted using a Bonferroni
      multiple comparison adjustment.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This study was one of three multi-site clinical trials conducted in three different vulnerable populations under a similar protocol, with differences between protocols consisting of data collection specific to that vulnerable population. This included information such as use and timing of opioid maintenance therapy for individuals with opioid-use disorder or additional assessments of anxiety and depression for individuals with affective disorders. In order to explore potential differences across individuals with different vulnerabilities, data from all three studies were combined for analysis. A vulnerable population-by-condition or population-by- condition-by-time interaction term was included in all analyses. In the event that these interaction terms were statistically significant, all pairwise comparisons were conducted using a Bonferroni multiple comparison adjustment. Please see Statistical Analysis Plan for more details.
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Cigarettes Per Day (CPD)
time frame: 12 weeks
description: Participant reported number of cigarettes smoked per day at Week 12
arm group label: 0.8 mg nicotine
arm group type: Experimental
description: 0.8 mg nicotine very low nicotine content cigarettes
arm group label: 0.12 mg nicotine
arm group type: Experimental
description: 0.12 mg nicotine very low nicotine content cigarettes
arm group label: 0.03 mg nicotine
arm group type: Experimental
description: 0.03 mg nicotine very low nicotine content cigarettes
intervention type: Other
intervention name: Very low nicotine content cigarettes
description: Very low nicotine content cigarettes
arm group label: 0.03 mg nicotine
arm group label: 0.12 mg nicotine
arm group label: 0.8 mg nicotine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Stephen T. Higgins, Ph.D.
role: Study Director
affiliation: University of Vermont
last name: Stacey Sigmon, Ph.D.
role: Principal Investigator
affiliation: University of Vermont
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Vermont
investigator full name: Stephen T. Higgins, PhD
investigator title: Professor
mesh term: Tobacco Use Disorder
mesh term: Nicotine
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 