<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/NCT03232827</url>
  </required_header>
  <id_info>
    <org_study_id>1R03DA041928-01A1</org_study_id>
    <secondary_id>1R03DA041928-01A1</secondary_id>
    <nct_id>NCT03232827</nct_id>
  </id_info>
  <brief_title>The Impact of Waterpipe Tobacco Flavors on Waterpipe Smoking Intentions, Perceptions, Patterns, and Toxicant Exposure</brief_title>
  <official_title>The Impact of Waterpipe Tobacco Flavors on Waterpipe Smoking Intentions, Perceptions, Patterns, and Toxicant Exposure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oklahoma</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Virginia Commonwealth University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>American University of Beirut Medical Center</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 Oklahoma</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>
      The overall aim of the current study is to determine if flavorings contribute to the&#xD;
      initiation and maintenance of waterpipe (WP) smoking and also influence how a WP is smoked,&#xD;
      which has implications for both risk of dependence but also smokers' level of exposure to&#xD;
      tobacco-related toxicants. A total of 94 current WP smokers (47 low dependent, 47 high&#xD;
      dependent) will be recruited. Based on our team's previous studies we conservatively assume a&#xD;
      20% attrition rate; thus, we will need to recruit 94 participants to have 76 complete all&#xD;
      four sessions. Consistent with other laboratory studies of waterpipe smoking, participants&#xD;
      who meet the following eligibility criteria will be asked to take part in the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After completing the initial screening by phone, participants will be informed of the study&#xD;
      procedures and invited to the lab to complete three WP smoking sessions. Participants will&#xD;
      perform exhaled carbon monoxide testing (eCO&lt; 10ppm) and confirm that they have not used any&#xD;
      nicotine/tobacco/marijuana products over the last 12 hours. Pregnancy exclusion will also be&#xD;
      confirmed with a urine test, and pregnancy tests will be completed at each visit throughout&#xD;
      the study. Participants will be randomized and complete study procedures in self-selected&#xD;
      dyads. The sessions will be counterbalanced and include: 1) smoking preferred&#xD;
      flavored-sweetened WP tobacco, 2) smoking unflavored-sweetened WP tobacco, and 3) smoking&#xD;
      unflavored-very low sweetened WP tobacco. Participants will complete all three study visits&#xD;
      in the laboratory. Pre-session abstinence from tobacco for at least 12 hours will be&#xD;
      mandatory for all participants. Abstinence will be confirmed via participant self-report and&#xD;
      an exhaled carbon monoxide monitor (&lt; 20 ppm) for tobacco use. Participant dyads will smoke&#xD;
      hookah ad libitum for up to 1 hour. This procedure will be completed for all visits.&#xD;
      Participants will also complete a minimum 48-hour washout period between sessions.&#xD;
&#xD;
      Participants will not be allowed to eat, drink or use their phone during the session.&#xD;
      Initially, one piece of charcoal will be lit and placed on top of the foil. Our preliminary&#xD;
      studies, as well as other WP laboratory trials, indicate that one piece of charcoal will not&#xD;
      be sufficient for one WP session; thus, participants will be provided additional pre-weighed&#xD;
      pieces to use as they wish. Use of additional charcoal will be recorded. Participants will&#xD;
      smoke ad libitum and a WP puff topography device will discretely record smoking behavior&#xD;
      throughout the session, including puff duration, number of puffs, puff volume, puff flow&#xD;
      rate, and time between puffs. Blood samples (15mL per sample) and eCO will be collected&#xD;
      immediately pre- and post-waterpipe session. Self-report measures will be administered.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2017</start_date>
  <completion_date type="Actual">March 12, 2018</completion_date>
  <primary_completion_date type="Actual">March 12, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Level of Smoke Inhalation Measured by Topography Device</measure>
    <time_frame>6 months</time_frame>
    <description>Participants will complete one ad-lib puffing session at each visit. Levels of smoke inhalation will be measured throughout each ad-lib puffing session. Flavored-sweetened WP tobacco will be associated with longer and more frequent puffing resulting in the greatest overall levels of smoke inhalation (mL of smoke inhaled).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Levels of Smoke Inhalation Between High vs. Low Dependent WP</measure>
    <time_frame>6 months</time_frame>
    <description>Waterpipe dependence for participants will be determined at baseline. Participants will complete one ad-lib puffing session at each visit. Levels of smoke inhalation will be measured throughout each ad-lib puffing session. Flavored-sweetened WP tobacco will be associated with longer and more frequent puffing resulting in the greatest overall levels of smoke inhalation (mL of smoke inhaled). Compared to high dependence users smoking unflavored WP tobacco, low dependence users will show greater declines in (H2a) puff frequency and duration resulting in lower levels of smoke inhalation</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">91</enrollment>
  <condition>Smoking, Hookah</condition>
  <condition>Waterpipe Smoking</condition>
  <arm_group>
    <arm_group_label>Flavored-sweetened</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Flavored-sweetened (FS) WP tobacco will be associated with longer and more frequent puffing resulting in the greatest overall levels of smoke inhalation (mL of smoke inhaled), highest abuse potential, and greatest levels of exposure to nicotine and carbon monoxide (CO). , followed by unflavored-sweetened WP, and lastly unflavored-very low sweetened WP. (H1d) A majority of WP smokers will report having initiated WP smoking with flavored-sweetened tobacco and report flavoring as an important reason for trying WP.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Unflavored-sweetened</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Unflavored-sweetened (US) WP will be associated with the second longest and slightly less frequent puffing than FS resulting in the second greatest overall levels of smoke inhalation (mL of smoke inhaled), abuse potential, and levels of exposure to nicotine and carbon monoxide (CO).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Unflavored very low sweetened</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Unflavored-very low sweetened (UU) WP will be associated with the shortest and the least frequent puffing resulting in the least overall levels of smoke inhalation (mL of smoke inhaled), abuse potential, and levels of exposure to nicotine and carbon monoxide (CO).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Flavored-very low sweetened waterpipe</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Flavored-very low sweetened WP will be associated with the third longest and slightly less frequent puffing than US resulting in the third greatest overall levels of smoke inhalation (mL of smoke inhaled), abuse potential, and levels of exposure to nicotine and carbon monoxide (CO).</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Flavored-Sweetened Waterpipe Tobacco</intervention_name>
    <description>Pre-weighed flavored-sweetened waterpipe tobacco will be prepared.</description>
    <arm_group_label>Flavored-sweetened</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Unflavored-sweetened waterpipe tobacco</intervention_name>
    <description>Pre-weighed unflavored-sweetened waterpipe tobacco will be prepared.</description>
    <arm_group_label>Unflavored-sweetened</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Unflavored-very low sweetened waterpipe tobacco</intervention_name>
    <description>Pre-weighed unflavored-very low sweetened waterpipe tobacco will be prepared.</description>
    <arm_group_label>Unflavored very low sweetened</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Flavored-very low sweetened waterpipe</intervention_name>
    <description>Pre-weighed flavored-very low sweetened waterpipe tobacco will be prepared.</description>
    <arm_group_label>Flavored-very low sweetened waterpipe</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  current water pipe smoker for at least the past 6 months&#xD;
&#xD;
          -  smoke water pipe at least 3 times in the last 6 months&#xD;
&#xD;
          -  Lebanese Waterpipe Dependence Scale-11 (LWDS-11) score of ≤9 (Low Dependence) or ≥10&#xD;
             (High Dependence)&#xD;
&#xD;
          -  between 18-50 years old&#xD;
&#xD;
          -  willing to provide informed consent&#xD;
&#xD;
          -  abstain from all tobacco, nicotine, and marijuana use for at least 12 hours prior to&#xD;
             each of the three sessions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  self-reported diagnosis of lung disease including asthma, cystic fibrosis, or chronic&#xD;
             obstructive pulmonary disease&#xD;
&#xD;
          -  currently pregnant, planning to become pregnant, or breastfeeding&#xD;
&#xD;
          -  history of cardiac event or distress within the last 3 months&#xD;
&#xD;
          -  any use of other illicit drugs during the last 30 days.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Theodore Wagener, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Oklahoma</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Oklahoma Health Sciences Center Tobacco Research Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>June 22, 2017</study_first_submitted>
  <study_first_submitted_qc>July 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2017</study_first_posted>
  <results_first_submitted>April 1, 2019</results_first_submitted>
  <results_first_submitted_qc>June 21, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">June 24, 2019</results_first_posted>
  <last_update_submitted>June 21, 2019</last_update_submitted>
  <last_update_submitted_qc>June 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 24, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 18, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/27/NCT03232827/ICF_000.pdf</document_url>
    </provided_document>
    <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>December 18, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/27/NCT03232827/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 207 individuals were identified as eligible for study participation. Study personnel contacted the individuals by telephone to schedule their initial visit. 91 were consented and enrolled.</recruitment_details>
      <pre_assignment_details>Subjects who were eligible &amp; presented to initial visit 12 hour tobacco abstinent were randomized. Subjects were randomized to 1 of 36 session sequences &amp; completed up to four smoking sessions. 2 subjects were not nicotine abstinent at their initial visit, were rescheduled &amp; lost to follow-up.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>All Interventions</title>
          <description>Participants will be randomized and complete study procedures in self-selected dyads. The sessions will be counterbalanced and include: 1) smoking preferred flavored-sweetened WP tobacco 2) smoking unflavored-sweetened WP Tobacco and 3) smoking preferred flavored-very low sweetened WP tobacco and 4) smoking unflavored-very low sweetened WP tobacco. Participants will complete all four study visits in the laboratory. Pre-session abstinence from tobacco for at least 12 hours will be mandatory for all participants. Abstinence will be confirmed via participant self-report and an exhaled carbon monoxide monitor (&lt; 20 ppm) for tobacco use. Participant dyads will first complete a 10-minute puffing session separated by 30-second intervals with the prepared hookah and then smoke ad libitum for up to 1 hour. This procedure will be completed for all visits. Participants will also complete a minimum 48-hour washout period between sessions.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Flavored-sweetened (FS)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="80"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="80"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Unflavored-sweetened (US)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="86"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="86"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Unflavored-very Low Sweetened (UU)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="66"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="66"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Flavored-very Low Sweetened</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="66"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="66"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Study Participants</title>
          <description>Participants completed up to 4 smoking sessions and were randomized to 1 of 36 session sequences: 1) FS - UU - US, 2) UU - FS - US, 3) US - UU - FS, 4) FS - US - UU, 5) US - FS - UU, 6) UU - US - FS, 7) UU - FU - US - FS, 8) UU - FU - FS - US, 9) UU - US - FS - FU, 10) UU - US - FU - FS, 11) UU - FS - US - FU, 12) UU - FS - FU - US, 13) FU - UU - US - FS, 14) FU - UU - FS - US, 15) FU - US - FS - UU, 16) FU - US - UU - FS, 17) FU - FS - UU - US, 18) FU - FS - US - UU, 19) US - UU - FU - FS, 20) US - UU - FS - FU, 21) US - FU - UU - FS, 22) US - FU - FS - UU, 23) US - FS - UU - FU, 24) US - FS - FU - UU, 25) FS - UU - FU - US, 26) FS - UU - US - FU, 27) FS - FU - UU - US, 28) FS - FU - US - UU, 29) FS - US - FU - UU, 30) FS - US - UU - FU, 31) UU - FU - FS - US, 32) FS - UU - FU - US, 33) FU - FS - US - UU, 34) US - UU - FS - FU, 35) FU - US - UU - FS, 36) UU - US - FU - FS. A fourth arm (FU) was added to the study one month after the study started.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="89"/>
          </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="23.98" spread="5.58"/>
                  </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="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </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="89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Waterpipe smoking days per month</title>
          <units>Days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.5" spread="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Waterpipe dependence</title>
          <description>WP dependence will be measured using the Lebanese Waterpipe Dependence Scale-11. ≤9 (Low Dependence) or ≥10 (High Dependence). This validated scale is correlated significantly with nicotine exposure, CO, and WP use frequency. The 11 scale items were summed to calculate the total WP dependence score. The cutoffs for low vs high dependence are as follows: ≤9 (Low Dependence) or ≥10 (High Dependence).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Low Dependence</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                  </measurement_list>
                </category>
                <category>
                  <title>High Dependence</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Level of Smoke Inhalation Measured by Topography Device</title>
        <description>Participants will complete one ad-lib puffing session at each visit. Levels of smoke inhalation will be measured throughout each ad-lib puffing session. Flavored-sweetened WP tobacco will be associated with longer and more frequent puffing resulting in the greatest overall levels of smoke inhalation (mL of smoke inhaled).</description>
        <time_frame>6 months</time_frame>
        <population>1 participant was not included in analysis due to self-withdraw. Participants who completed one or more of the individual intervention visits were included.</population>
        <group_list>
          <group group_id="O1">
            <title>Flavored-sweetened</title>
            <description>Flavored-sweetened (FS) WP tobacco will be associated with longer and more frequent puffing resulting in the greatest overall levels of smoke inhalation (mL of smoke inhaled), highest abuse potential, and greatest levels of exposure to nicotine and carbon monoxide (CO). , followed by unflavored-sweetened WP, and lastly unflavored-very low sweetened WP. (H1d) A majority of WP smokers will report having initiated WP smoking with flavored-sweetened tobacco and report flavoring as an important reason for trying WP.&#xD;
Flavored-Sweetened Waterpipe Tobacco: Pre-weighed flavored-sweetened waterpipe tobacco will be prepared.</description>
          </group>
          <group group_id="O2">
            <title>Unflavored-sweetened</title>
            <description>Unflavored-sweetened (US) WP will be associated with the second longest and slightly less frequent puffing than FS resulting in the second greatest overall levels of smoke inhalation (mL of smoke inhaled), abuse potential, and levels of exposure to nicotine and carbon monoxide (CO).&#xD;
Unflavored-sweetened waterpipe tobacco: Pre-weighed unflavored-sweetened waterpipe tobacco will be prepared.</description>
          </group>
          <group group_id="O3">
            <title>Unflavored Very Low Sweetened</title>
            <description>Unflavored-very low sweetened (UU) WP will be associated with the shortest and the least frequent puffing resulting in the least overall levels of smoke inhalation (mL of smoke inhaled), abuse potential, and levels of exposure to nicotine and carbon monoxide (CO).&#xD;
Unflavored-very low sweetened waterpipe tobacco: Pre-weighed unflavored-very low sweetened waterpipe tobacco will be prepared.</description>
          </group>
          <group group_id="O4">
            <title>Flavored-very Low Sweetened Waterpipe</title>
            <description>Flavored-very low sweetened WP will be associated with the third longest and slightly less frequent puffing than US resulting in the third greatest overall levels of smoke inhalation (mL of smoke inhaled), abuse potential, and levels of exposure to nicotine and carbon monoxide (CO).&#xD;
Flavored-very low sweetened waterpipe: Pre-weighed flavored-very low sweetened waterpipe tobacco will be prepared.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Smoke Inhalation Measured by Topography Device</title>
          <description>Participants will complete one ad-lib puffing session at each visit. Levels of smoke inhalation will be measured throughout each ad-lib puffing session. Flavored-sweetened WP tobacco will be associated with longer and more frequent puffing resulting in the greatest overall levels of smoke inhalation (mL of smoke inhaled).</description>
          <population>1 participant was not included in analysis due to self-withdraw. Participants who completed one or more of the individual intervention visits were included.</population>
          <units>Liters</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="86"/>
                <count group_id="O3" value="66"/>
                <count group_id="O4" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.96" spread="5.46"/>
                    <measurement group_id="O2" value="77.79" spread="5.89"/>
                    <measurement group_id="O3" value="63.17" spread="5.87"/>
                    <measurement group_id="O4" value="51.60" spread="4.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Levels of Smoke Inhalation Between High vs. Low Dependent WP</title>
        <description>Waterpipe dependence for participants will be determined at baseline. Participants will complete one ad-lib puffing session at each visit. Levels of smoke inhalation will be measured throughout each ad-lib puffing session. Flavored-sweetened WP tobacco will be associated with longer and more frequent puffing resulting in the greatest overall levels of smoke inhalation (mL of smoke inhaled). Compared to high dependence users smoking unflavored WP tobacco, low dependence users will show greater declines in (H2a) puff frequency and duration resulting in lower levels of smoke inhalation</description>
        <time_frame>6 months</time_frame>
        <population>1 participant was not included in analysis due to self-withdraw. Participants who completed one or more of the individual intervention visits were included.</population>
        <group_list>
          <group group_id="O1">
            <title>Flavored-sweetened</title>
            <description>Flavored-sweetened (FS) WP tobacco will be associated with longer and more frequent puffing resulting in the greatest overall levels of smoke inhalation (mL of smoke inhaled), highest abuse potential, and greatest levels of exposure to nicotine and carbon monoxide (CO). , followed by unflavored-sweetened WP, and lastly unflavored-very low sweetened WP. (H1d) A majority of WP smokers will report having initiated WP smoking with flavored-sweetened tobacco and report flavoring as an important reason for trying WP.&#xD;
Flavored-Sweetened Waterpipe Tobacco: Pre-weighed flavored-sweetened waterpipe tobacco will be prepared.</description>
          </group>
          <group group_id="O2">
            <title>Unflavored-sweetened</title>
            <description>Unflavored-sweetened (US) WP will be associated with the second longest and slightly less frequent puffing than FS resulting in the second greatest overall levels of smoke inhalation (mL of smoke inhaled), abuse potential, and levels of exposure to nicotine and carbon monoxide (CO).&#xD;
Unflavored-sweetened waterpipe tobacco: Pre-weighed unflavored-sweetened waterpipe tobacco will be prepared.</description>
          </group>
          <group group_id="O3">
            <title>Unflavored Very Low Sweetened</title>
            <description>Unflavored-very low sweetened (UU) WP will be associated with the shortest and the least frequent puffing resulting in the least overall levels of smoke inhalation (mL of smoke inhaled), abuse potential, and levels of exposure to nicotine and carbon monoxide (CO).&#xD;
Unflavored-very low sweetened waterpipe tobacco: Pre-weighed unflavored-very low sweetened waterpipe tobacco will be prepared.</description>
          </group>
          <group group_id="O4">
            <title>Flavored-very Low Sweetened Waterpipe</title>
            <description>Flavored-very low sweetened WP will be associated with the third longest and slightly less frequent puffing than US resulting in the third greatest overall levels of smoke inhalation (mL of smoke inhaled), abuse potential, and levels of exposure to nicotine and carbon monoxide (CO).&#xD;
Flavored-very low sweetened waterpipe: Pre-weighed flavored-very low sweetened waterpipe tobacco will be prepared.</description>
          </group>
        </group_list>
        <measure>
          <title>Levels of Smoke Inhalation Between High vs. Low Dependent WP</title>
          <description>Waterpipe dependence for participants will be determined at baseline. Participants will complete one ad-lib puffing session at each visit. Levels of smoke inhalation will be measured throughout each ad-lib puffing session. Flavored-sweetened WP tobacco will be associated with longer and more frequent puffing resulting in the greatest overall levels of smoke inhalation (mL of smoke inhaled). Compared to high dependence users smoking unflavored WP tobacco, low dependence users will show greater declines in (H2a) puff frequency and duration resulting in lower levels of smoke inhalation</description>
          <population>1 participant was not included in analysis due to self-withdraw. Participants who completed one or more of the individual intervention visits were included.</population>
          <units>Liters</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="86"/>
                <count group_id="O3" value="66"/>
                <count group_id="O4" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Low Dependence</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="48"/>
                    <count group_id="O2" value="48"/>
                    <count group_id="O3" value="41"/>
                    <count group_id="O4" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.18" spread="5.02"/>
                    <measurement group_id="O2" value="55.85" spread="5.84"/>
                    <measurement group_id="O3" value="46.18" spread="6.03"/>
                    <measurement group_id="O4" value="39.43" spread="4.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>High Dependence</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                    <count group_id="O2" value="38"/>
                    <count group_id="O3" value="25"/>
                    <count group_id="O4" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.15" spread="6.26"/>
                    <measurement group_id="O2" value="57.31" spread="6.95"/>
                    <measurement group_id="O3" value="51.07" spread="7.26"/>
                    <measurement group_id="O4" value="33.96" spread="5.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Participants were monitored over the 6 months they were in the study. Adverse event information was collected and assessed at each visit.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Flavored Sweetened</title>
          <description>Flavored-sweetened (FS) WP tobacco will be associated with longer and more frequent puffing resulting in the greatest overall levels of smoke inhalation (mL of smoke inhaled), highest abuse potential, and greatest levels of exposure to nicotine and carbon monoxide (CO). , followed by unflavored-sweetened WP, and lastly unflavored-very low sweetened WP. (H1d) A majority of WP smokers will report having initiated WP smoking with flavored-sweetened tobacco and report flavoring as an important reason for trying WP.</description>
        </group>
        <group group_id="E2">
          <title>Unflavored Sweetened</title>
          <description>Unflavored-sweetened (US) WP will be associated with the second longest and slightly less frequent puffing than FS resulting in the second greatest overall levels of smoke inhalation (mL of smoke inhaled), abuse potential, and levels of exposure to nicotine and carbon monoxide (CO).&#xD;
Unflavored-sweetened waterpipe tobacco: Pre-weighed unflavored-sweetened waterpipe tobacco will be prepared.</description>
        </group>
        <group group_id="E3">
          <title>Unflavored Very Low Sweetened</title>
          <description>Unflavored-very low sweetened (UU) WP will be associated with the shortest and the least frequent puffing resulting in the least overall levels of smoke inhalation (mL of smoke inhaled), abuse potential, and levels of exposure to nicotine and carbon monoxide (CO).&#xD;
Unflavored-very low sweetened waterpipe tobacco: Pre-weighed unflavored-very low sweetened waterpipe tobacco will be prepared.</description>
        </group>
        <group group_id="E4">
          <title>Flavored-very Low Sweetened Waterpipe</title>
          <description>Flavored-very low sweetened WP will be associated with the third longest and slightly less frequent puffing than US resulting in the third greatest overall levels of smoke inhalation (mL of smoke inhaled), abuse potential, and levels of exposure to nicotine and carbon monoxide (CO).&#xD;
Flavored-very low sweetened waterpipe: Pre-weighed flavored-very low sweetened waterpipe tobacco will be prepared.</description>
        </group>
      </group_list>
      <serious_events>
        <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="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="66"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="66"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="66"/>
              </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>Dr. Theodore Wagener</name_or_title>
      <organization>UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR</organization>
      <phone>405-271-4407 ext 50486</phone>
      <email>theodore-wagener@ouhsc.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/NCT03232827
org study id: 1R03DA041928-01A1
secondary id: 1R03DA041928-01A1
nct id: NCT03232827
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
The overall aim of the current study is to determine if flavorings contribute to the
      initiation and maintenance of waterpipe (WP) smoking and also influence how a WP is smoked,
      which has implications for both risk of dependence but also smokers' level of exposure to
      tobacco-related toxicants. A total of 94 current WP smokers (47 low dependent, 47 high
      dependent) will be recruited. Based on our team's previous studies we conservatively assume a
      20% attrition rate; thus, we will need to recruit 94 participants to have 76 complete all
      four sessions. Consistent with other laboratory studies of waterpipe smoking, participants
      who meet the following eligibility criteria will be asked to take part in the study.
After completing the initial screening by phone, participants will be informed of the study
      procedures and invited to the lab to complete three WP smoking sessions. Participants will
      perform exhaled carbon monoxide testing (eCO< 10ppm) and confirm that they have not used any
      nicotine/tobacco/marijuana products over the last 12 hours. Pregnancy exclusion will also be
      confirmed with a urine test, and pregnancy tests will be completed at each visit throughout
      the study. Participants will be randomized and complete study procedures in self-selected
      dyads. The sessions will be counterbalanced and include: 1) smoking preferred
      flavored-sweetened WP tobacco, 2) smoking unflavored-sweetened WP tobacco, and 3) smoking
      unflavored-very low sweetened WP tobacco. Participants will complete all three study visits
      in the laboratory. Pre-session abstinence from tobacco for at least 12 hours will be
      mandatory for all participants. Abstinence will be confirmed via participant self-report and
      an exhaled carbon monoxide monitor (< 20 ppm) for tobacco use. Participant dyads will smoke
      hookah ad libitum for up to 1 hour. This procedure will be completed for all visits.
      Participants will also complete a minimum 48-hour washout period between sessions.

      Participants will not be allowed to eat, drink or use their phone during the session.
      Initially, one piece of charcoal will be lit and placed on top of the foil. Our preliminary
      studies, as well as other WP laboratory trials, indicate that one piece of charcoal will not
      be sufficient for one WP session; thus, participants will be provided additional pre-weighed
      pieces to use as they wish. Use of additional charcoal will be recorded. Participants will
      smoke ad libitum and a WP puff topography device will discretely record smoking behavior
      throughout the session, including puff duration, number of puffs, puff volume, puff flow
      rate, and time between puffs. Blood samples (15mL per sample) and eCO will be collected
      immediately pre- and post-waterpipe session. Self-report measures will be administered.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Health Services Research
masking: Single (Participant)
measure: Level of Smoke Inhalation Measured by Topography Device
time frame: 6 months
description: Participants will complete one ad-lib puffing session at each visit. Levels of smoke inhalation will be measured throughout each ad-lib puffing session. Flavored-sweetened WP tobacco will be associated with longer and more frequent puffing resulting in the greatest overall levels of smoke inhalation (mL of smoke inhaled).
measure: Levels of Smoke Inhalation Between High vs. Low Dependent WP
time frame: 6 months
description: Waterpipe dependence for participants will be determined at baseline. Participants will complete one ad-lib puffing session at each visit. Levels of smoke inhalation will be measured throughout each ad-lib puffing session. Flavored-sweetened WP tobacco will be associated with longer and more frequent puffing resulting in the greatest overall levels of smoke inhalation (mL of smoke inhaled). Compared to high dependence users smoking unflavored WP tobacco, low dependence users will show greater declines in (H2a) puff frequency and duration resulting in lower levels of smoke inhalation
arm group label: Flavored-sweetened
arm group type: Active Comparator
description: Flavored-sweetened (FS) WP tobacco will be associated with longer and more frequent puffing resulting in the greatest overall levels of smoke inhalation (mL of smoke inhaled), highest abuse potential, and greatest levels of exposure to nicotine and carbon monoxide (CO). , followed by unflavored-sweetened WP, and lastly unflavored-very low sweetened WP. (H1d) A majority of WP smokers will report having initiated WP smoking with flavored-sweetened tobacco and report flavoring as an important reason for trying WP.
arm group label: Unflavored-sweetened
arm group type: Active Comparator
description: Unflavored-sweetened (US) WP will be associated with the second longest and slightly less frequent puffing than FS resulting in the second greatest overall levels of smoke inhalation (mL of smoke inhaled), abuse potential, and levels of exposure to nicotine and carbon monoxide (CO).
arm group label: Unflavored very low sweetened
arm group type: Active Comparator
description: Unflavored-very low sweetened (UU) WP will be associated with the shortest and the least frequent puffing resulting in the least overall levels of smoke inhalation (mL of smoke inhaled), abuse potential, and levels of exposure to nicotine and carbon monoxide (CO).
arm group label: Flavored-very low sweetened waterpipe
arm group type: Active Comparator
description: Flavored-very low sweetened WP will be associated with the third longest and slightly less frequent puffing than US resulting in the third greatest overall levels of smoke inhalation (mL of smoke inhaled), abuse potential, and levels of exposure to nicotine and carbon monoxide (CO).
intervention type: Behavioral
intervention name: Flavored-Sweetened Waterpipe Tobacco
description: Pre-weighed flavored-sweetened waterpipe tobacco will be prepared.
arm group label: Flavored-sweetened
intervention type: Behavioral
intervention name: Unflavored-sweetened waterpipe tobacco
description: Pre-weighed unflavored-sweetened waterpipe tobacco will be prepared.
arm group label: Unflavored-sweetened
intervention type: Behavioral
intervention name: Unflavored-very low sweetened waterpipe tobacco
description: Pre-weighed unflavored-very low sweetened waterpipe tobacco will be prepared.
arm group label: Unflavored very low sweetened
intervention type: Behavioral
intervention name: Flavored-very low sweetened waterpipe
description: Pre-weighed flavored-very low sweetened waterpipe tobacco will be prepared.
arm group label: Flavored-very low sweetened waterpipe
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Theodore Wagener, PhD
role: Principal Investigator
affiliation: University of Oklahoma
facility: 
country: United States
responsible party type: Sponsor
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 