<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/NCT03262233</url>
  </required_header>
  <id_info>
    <org_study_id>2017-0433</org_study_id>
    <nct_id>NCT03262233</nct_id>
  </id_info>
  <brief_title>Stress Neuroadaptation in Tobacco Dependence</brief_title>
  <official_title>Clinical Relevance of Stress Neuroadaptation in Tobacco Dependence</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Wisconsin, Madison</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of the current study is to evaluate the validity of the No Shock, Predictable&#xD;
      Shock, Unpredictable Shock (NPU) stressor task for use as a surrogate endpoint to predict&#xD;
      short-term clinical outcomes among smokers during a smoking cessation attempt.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Smokers recruited for this study are randomly assigned at a screening session to complete the&#xD;
      NPU stressor task pre-quit or post-quit (i.e., nicotine deprived or non-deprived).&#xD;
      Participants are also randomized to receive either placebo or active combination nicotine&#xD;
      replacement therapy (NRT; patches and lozenges) for a two week smoking cessation period. The&#xD;
      NPU stressor task measures stressor reactivity to predictable and unpredictable stressors&#xD;
      (i.e., electric shock). Startle potentiation during predictable and unpredictable stressors&#xD;
      (relative to no-shock) provides the primary measures of stressor reactivity in this task.&#xD;
      Predictable and unpredictable startle potentiation are used to calculate overall stressor&#xD;
      reactivity and selective unpredictable stressor reactivity. Further detail on these&#xD;
      reactivity measures is provided in the Independent Variables section. Detail on the&#xD;
      quantification of startle potentiation is provided at the end of this registration.&#xD;
&#xD;
      Smokers provide three weeks (1 week pre-quit, 2 weeks post-quit) of brief 4x daily, real-time&#xD;
      web-survey reports of recent cigarette use, NRT use, and other measures not relevant to this&#xD;
      study's purpose on the participants' smartphones. At two weeks post-quit, smokers are&#xD;
      scheduled for a laboratory visit where participants provide an additional report via staff&#xD;
      interview of any smoking during the two-week smoking cessation period.&#xD;
&#xD;
      The stressor reactivity measures from the NPU task will be tested as predictors of clinical&#xD;
      outcome (i.e., continuous abstinence during the two-week cessation period) to evaluate the&#xD;
      validity of each as surrogate endpoints for use in research on stress mechanisms in smoking&#xD;
      relapse. Deprivation status at the time of the NPU stressor task will be examined as a&#xD;
      moderator of the effect of stressor reactivity to determine if the surrogate endpoints&#xD;
      predict clinical outcome generally or only as deprivation increases.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2015</start_date>
  <completion_date type="Actual">February 20, 2018</completion_date>
  <primary_completion_date type="Actual">February 20, 2018</primary_completion_date>
  <phase>Phase 4</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>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Stressor Reactivity</measure>
    <time_frame>up to 24 hours after start of cessation attempt (deprived groups); during normal smoking prior to quit attempt, ie. Baseline (non-deprived groups)</time_frame>
    <description>The average of unpredictable startle potentiation and predictable startle potentiation during the first administration of the NPU stressor task.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Relative Unpredictable Stressor Reactivity</measure>
    <time_frame>up to 24 hours post cessation attempt (deprived groups); during normal smoking prior to quit attempt, ie. Baseline (non-deprived groups)</time_frame>
    <description>Unpredictable startle potentiation minus predictable startle potentiation during the first administration of the NPU stressor task</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Overall Stressor Reactivity</measure>
    <time_frame>baseline and up to 14 days post cessation attempt (non-deprived groups); baseline and up to 24 hours post quit attempt (deprived groups)</time_frame>
    <description>A difference score of overall stressor reactivity during the second administration of the NPU stressor task relative to the first NPU stressor task</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Relative Unpredictable Stressor Reactivity</measure>
    <time_frame>baseline and up to 14 days post cessation attempt (non-deprived groups); baseline and up to 24 hours post quit attempt (deprived groups)</time_frame>
    <description>A difference score of relative unpredictable stressor reactivity during the second administration of the NPU stressor task relative to the first NPU stressor task</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">226</enrollment>
  <condition>Nicotine Dependence</condition>
  <arm_group>
    <arm_group_label>Active Deprived</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>21 mg nicotine patches and 2 mg nicotine lozenges&#xD;
+ First NPU task takes place 24 hours after start of quit attempt</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active Non-deprived</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>21 mg nicotine patches and 2 mg nicotine lozenges&#xD;
+ First NPU task takes place during normal smoking prior to quit attempt</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Deprived</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Placebo patches and placebo lozenges&#xD;
+ First NPU task takes place 24 hours after start of quit attempt</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Non-deprived</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Placebo patches and placebo lozenges&#xD;
+ First NPU task takes place during normal smoking prior to quit attempt</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>nicotine</intervention_name>
    <arm_group_label>Active Deprived</arm_group_label>
    <arm_group_label>Active Non-deprived</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>placebo</intervention_name>
    <arm_group_label>Placebo Deprived</arm_group_label>
    <arm_group_label>Placebo Non-deprived</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  cigarette use over 10 cigarettes/day for over two years;&#xD;
&#xD;
          -  smoking within the first 30 minutes of waking up&#xD;
&#xD;
          -  expired air carbon monoxide (CO) level &gt;6 ppm&#xD;
&#xD;
          -  self-reported motivation to quit smoking&#xD;
&#xD;
          -  and an agreement to respond to ecological momentary assessment prompts (via SMS)&#xD;
             throughout the day for three weeks.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Health screening are performed by questionnaire and reviewed by study staff (RA or&#xD;
             Research Specialist) to ensure that smokers can safely use the nicotine patch and&#xD;
             lozenge. Specifically, smokers will be excluded for FDA contraindications for nicotine&#xD;
             replacement therapy (i.e., no uncontrolled hypertension, recent myocardial infarction,&#xD;
             diabetes, heart disease, asthma, stomach ulcers).&#xD;
&#xD;
          -  All women of child-bearing potential will be required to agree to use an approved&#xD;
             method of birth control to prevent pregnancy during the course of the study.&#xD;
&#xD;
          -  All participants will report no medical or psychiatric condition that would&#xD;
             contraindicate exposure to electric shock.&#xD;
&#xD;
          -  Participants with uncorrected auditory or visual problems will be excluded.&#xD;
&#xD;
        Additional Data Exclusions&#xD;
&#xD;
          1. As part of the NPU stressor task, smokers are asked to indicate if the participant&#xD;
             &quot;can be shocked in the next 5 seconds&quot; at various points during the task. Responses to&#xD;
             these questions are used to verify that the participant understands the cue-shock&#xD;
             contingencies. Smokers who answer &lt; 10 out of 14 questions correctly the NPU stressor&#xD;
             task during the experimental session will be excluded from all analyses and replaced.&#xD;
&#xD;
          2. Smokers with 20% of cue trials identified as artifact in the NPU task will be excluded&#xD;
             from all analyses and replaced.&#xD;
&#xD;
          3. The analysis will NOT exclude smokers who are startle non-responders given that the&#xD;
             use of these surrogate endpoints in practice would likely need to include these&#xD;
             individuals to avoid unnecessary data loss.&#xD;
&#xD;
          4. Smokers who do not report a complete abstinence between quit date/time and final&#xD;
             laboratory visit (which occurs 12-36 hours later) will be considered to not have quit&#xD;
             and will be excluded from all analyses and replaced.&#xD;
&#xD;
          5. Smokers for whom the investigators cannot definitively quantify an outcome with&#xD;
             respect to continuous abstinence will be excluded from all analyses and replaced. Any&#xD;
             report of smoking during the two-week cessation period (reported either during the 4x&#xD;
             daily web surveys or the laboratory visit at 2 weeks) is sufficient to code the smoker&#xD;
             to have lapsed (i.e., not continuously abstinent), even if the participants do not&#xD;
             complete the full two weeks of web surveys and/or the 2-week laboratory visit.&#xD;
             However, the status of smokers who report no smoking during the cessation attempt but&#xD;
             have both a high level of missing data from the web surveys (&gt; 25% of reports) and no&#xD;
             two-week laboratory visit report will be deemed uncertain. These smokers will be&#xD;
             excluded and replaced.&#xD;
&#xD;
          6. The investigators will conduct case analyses to identify participants who are model&#xD;
             outliers with Bonferroni-corrected studentized residuals p &lt; 0.05. These model&#xD;
             outliers will be excluded but NOT replaced (because the participants are not&#xD;
             identified until after data collection has been completed).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Wisconsin</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53706</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>August 23, 2017</study_first_submitted>
  <study_first_submitted_qc>August 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 25, 2017</study_first_posted>
  <results_first_submitted>March 1, 2019</results_first_submitted>
  <results_first_submitted_qc>April 1, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">April 23, 2019</results_first_posted>
  <last_update_submitted>April 1, 2019</last_update_submitted>
  <last_update_submitted_qc>April 1, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tobacco Use Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nicotine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>IPD will be shared on the data repository at Open Science Foundation</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>Data will be available on submission of first manuscript based on study</ipd_time_frame>
    <ipd_access_criteria>Data are completely open</ipd_access_criteria>
    <ipd_url>https://osf.io/dz9yu/</ipd_url>
  </patient_data>
  <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>May 30, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/33/NCT03262233/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Active Deprived</title>
          <description>21 mg nicotine patches and 2 mg nicotine lozenges&#xD;
+ First NPU task takes place 24 hours after start of quit attempt</description>
        </group>
        <group group_id="P2">
          <title>Active Non-Deprived</title>
          <description>21 mg nicotine patches and 2 mg nicotine lozenges&#xD;
+ First NPU task takes place during normal smoking prior to quit attempt</description>
        </group>
        <group group_id="P3">
          <title>Placebo Deprived</title>
          <description>Placebo patches and placebo lozenges&#xD;
+ First NPU task takes place 24 hours after start of quit attempt</description>
        </group>
        <group group_id="P4">
          <title>Placebo Non-deprived</title>
          <description>Placebo patches and placebo lozenges&#xD;
+ First NPU task takes place during normal smoking prior to quit attempt</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="53"/>
                <participants group_id="P2" count="53"/>
                <participants group_id="P3" count="59"/>
                <participants group_id="P4" count="61"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="32"/>
                <participants group_id="P3" count="34"/>
                <participants group_id="P4" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="21"/>
                <participants group_id="P3" count="25"/>
                <participants group_id="P4" count="29"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="21"/>
                <participants group_id="P4" count="13"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Declined due to shock</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="13"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>data collection artifact</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Active Deprived</title>
          <description>21 mg nicotine patches and 2 mg nicotine lozenges&#xD;
+ First NPU task takes place 24 hours after start of quit attempt</description>
        </group>
        <group group_id="B2">
          <title>Active Non-Deprived</title>
          <description>21 mg nicotine patches and 2 mg nicotine lozenges&#xD;
+ First NPU task takes place during normal smoking prior to quit attempt</description>
        </group>
        <group group_id="B3">
          <title>Placebo Deprived</title>
          <description>Placebo patches and placebo lozenges&#xD;
+ First NPU task takes place 24 hours after start of quit attempt</description>
        </group>
        <group group_id="B4">
          <title>Placebo Non-Deprived</title>
          <description>Placebo patches and placebo lozenges&#xD;
+ First NPU task takes place during normal smoking prior to quit attempt</description>
        </group>
        <group group_id="B5">
          <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="35"/>
            <count group_id="B2" value="32"/>
            <count group_id="B3" value="34"/>
            <count group_id="B4" value="32"/>
            <count group_id="B5" value="133"/>
          </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="38.1" spread="10.7"/>
                    <measurement group_id="B2" value="39.7" spread="12.4"/>
                    <measurement group_id="B3" value="40.6" spread="12.3"/>
                    <measurement group_id="B4" value="42" spread="11.3"/>
                    <measurement group_id="B5" value="40" spread="11.65"/>
                  </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="14"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="11"/>
                    <measurement group_id="B5" value="50"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="22"/>
                    <measurement group_id="B4" value="21"/>
                    <measurement group_id="B5" value="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="33"/>
                    <measurement group_id="B4" value="32"/>
                    <measurement group_id="B5" value="131"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </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="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="01"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="21"/>
                    <measurement group_id="B4" value="21"/>
                    <measurement group_id="B5" value="89"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </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="35"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="34"/>
                    <measurement group_id="B4" value="32"/>
                    <measurement group_id="B5" value="133"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Stressor Reactivity</title>
        <description>The average of unpredictable startle potentiation and predictable startle potentiation during the first administration of the NPU stressor task.</description>
        <time_frame>up to 24 hours after start of cessation attempt (deprived groups); during normal smoking prior to quit attempt, ie. Baseline (non-deprived groups)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Active Deprived</title>
            <description>21 mg nicotine patches and 2 mg nicotine lozenges&#xD;
+ First NPU task takes place 24 hours after start of quit attempt</description>
          </group>
          <group group_id="O2">
            <title>Active Non-deprived</title>
            <description>21 mg nicotine patches and 2 mg nicotine lozenges&#xD;
+ First NPU task takes place during normal smoking prior to quit attempt</description>
          </group>
          <group group_id="O3">
            <title>Placebo Deprived</title>
            <description>Placebo patches and placebo lozenges&#xD;
+ First NPU task takes place 24 hours after start of quit attempt</description>
          </group>
          <group group_id="O4">
            <title>Placebo Non-deprived</title>
            <description>Placebo patches and placebo lozenges&#xD;
+ First NPU task takes place during normal smoking prior to quit attempt</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Stressor Reactivity</title>
          <description>The average of unpredictable startle potentiation and predictable startle potentiation during the first administration of the NPU stressor task.</description>
          <units>microvolts</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.1" spread="23.0"/>
                    <measurement group_id="O2" value="22.5" spread="24.4"/>
                    <measurement group_id="O3" value="32.3" spread="29.6"/>
                    <measurement group_id="O4" value="16.9" spread="17.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Relative Unpredictable Stressor Reactivity</title>
        <description>Unpredictable startle potentiation minus predictable startle potentiation during the first administration of the NPU stressor task</description>
        <time_frame>up to 24 hours post cessation attempt (deprived groups); during normal smoking prior to quit attempt, ie. Baseline (non-deprived groups)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Active Deprived</title>
            <description>21 mg nicotine patches and 2 mg nicotine lozenges&#xD;
+ First NPU task takes place 24 hours after start of quit attempt</description>
          </group>
          <group group_id="O2">
            <title>Active Non-Deprived</title>
            <description>21 mg nicotine patches and 2 mg nicotine lozenges&#xD;
+ First NPU task takes place during normal smoking prior to quit attempt</description>
          </group>
          <group group_id="O3">
            <title>Placebo Deprived</title>
            <description>Placebo patches and placebo lozenges&#xD;
+ First NPU task takes place 24 hours after start of quit attempt</description>
          </group>
          <group group_id="O4">
            <title>Placebo Non-deprived</title>
            <description>Placebo patches and placebo lozenges&#xD;
+ First NPU task takes place during normal smoking prior to quit attempt</description>
          </group>
        </group_list>
        <measure>
          <title>Relative Unpredictable Stressor Reactivity</title>
          <description>Unpredictable startle potentiation minus predictable startle potentiation during the first administration of the NPU stressor task</description>
          <units>microvolts</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.77" spread="14.0"/>
                    <measurement group_id="O2" value="-7.91" spread="14.4"/>
                    <measurement group_id="O3" value="-6.06" spread="12.3"/>
                    <measurement group_id="O4" value="-4.99" spread="14.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Overall Stressor Reactivity</title>
        <description>A difference score of overall stressor reactivity during the second administration of the NPU stressor task relative to the first NPU stressor task</description>
        <time_frame>baseline and up to 14 days post cessation attempt (non-deprived groups); baseline and up to 24 hours post quit attempt (deprived groups)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Active Deprived</title>
            <description>21 mg nicotine patches and 2 mg nicotine lozenges&#xD;
+ First NPU task takes place 24 hours after start of quit attempt</description>
          </group>
          <group group_id="O2">
            <title>Active Non-Deprived</title>
            <description>21 mg nicotine patches and 2 mg nicotine lozenges&#xD;
+ First NPU task takes place during normal smoking prior to quit attempt</description>
          </group>
          <group group_id="O3">
            <title>Placebo Deprived</title>
            <description>Placebo patches and placebo lozenges&#xD;
+ First NPU task takes place 24 hours after start of quit attempt</description>
          </group>
          <group group_id="O4">
            <title>Placebo Non-deprived</title>
            <description>Placebo patches and placebo lozenges&#xD;
+ First NPU task takes place during normal smoking prior to quit attempt</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Overall Stressor Reactivity</title>
          <description>A difference score of overall stressor reactivity during the second administration of the NPU stressor task relative to the first NPU stressor task</description>
          <units>change in microvolts</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.94" spread="16.3"/>
                    <measurement group_id="O2" value="0.929" spread="13.0"/>
                    <measurement group_id="O3" value="-10.3" spread="24.0"/>
                    <measurement group_id="O4" value="4.78" spread="13.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Relative Unpredictable Stressor Reactivity</title>
        <description>A difference score of relative unpredictable stressor reactivity during the second administration of the NPU stressor task relative to the first NPU stressor task</description>
        <time_frame>baseline and up to 14 days post cessation attempt (non-deprived groups); baseline and up to 24 hours post quit attempt (deprived groups)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Active Deprived</title>
            <description>21 mg nicotine patches and 2 mg nicotine lozenges&#xD;
+ First NPU task takes place 24 hours after start of quit attempt</description>
          </group>
          <group group_id="O2">
            <title>Active Non-Deprived</title>
            <description>21 mg nicotine patches and 2 mg nicotine lozenges&#xD;
+ First NPU task takes place during normal smoking prior to quit attempt</description>
          </group>
          <group group_id="O3">
            <title>Placebo Deprived</title>
            <description>Placebo patches and placebo lozenges&#xD;
+ First NPU task takes place 24 hours after start of quit attempt</description>
          </group>
          <group group_id="O4">
            <title>Placebo Non-deprived</title>
            <description>Placebo patches and placebo lozenges&#xD;
+ First NPU task takes place during normal smoking prior to quit attempt</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Relative Unpredictable Stressor Reactivity</title>
          <description>A difference score of relative unpredictable stressor reactivity during the second administration of the NPU stressor task relative to the first NPU stressor task</description>
          <units>change in microvolts</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="32"/>
                <count group_id="O3" value="34"/>
                <count group_id="O4" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.95" spread="15.5"/>
                    <measurement group_id="O2" value="3.99" spread="14.8"/>
                    <measurement group_id="O3" value="0.889" spread="16.0"/>
                    <measurement group_id="O4" value="-1.35" spread="11.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>through 14 days post quit</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Active Deprived</title>
          <description>21 mg nicotine patches and 2 mg nicotine lozenges&#xD;
+ First NPU task takes place 24 hours after start of quit attempt</description>
        </group>
        <group group_id="E2">
          <title>Active Non-deprived</title>
          <description>21 mg nicotine patches and 2 mg nicotine lozenges&#xD;
+ First NPU task takes place during normal smoking prior to quit attempt</description>
        </group>
        <group group_id="E3">
          <title>Placebo Deprived</title>
          <description>Placebo patches and placebo lozenges&#xD;
+ First NPU task takes place 24 hours after start of quit attempt</description>
        </group>
        <group group_id="E4">
          <title>Placebo Non-deprived</title>
          <description>Placebo patches and placebo lozenges&#xD;
+ First NPU task takes place during normal smoking prior to quit attempt</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="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>John Curtin</name_or_title>
      <organization>UW-Madison</organization>
      <phone>608-262-0387</phone>
      <email>jjcurtin@wisc.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/NCT03262233
org study id: 2017-0433
nct id: NCT03262233
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The objective of the current study is to evaluate the validity of the No Shock, Predictable
      Shock, Unpredictable Shock (NPU) stressor task for use as a surrogate endpoint to predict
      short-term clinical outcomes among smokers during a smoking cessation attempt.
Smokers recruited for this study are randomly assigned at a screening session to complete the
      NPU stressor task pre-quit or post-quit (i.e., nicotine deprived or non-deprived).
      Participants are also randomized to receive either placebo or active combination nicotine
      replacement therapy (NRT; patches and lozenges) for a two week smoking cessation period. The
      NPU stressor task measures stressor reactivity to predictable and unpredictable stressors
      (i.e., electric shock). Startle potentiation during predictable and unpredictable stressors
      (relative to no-shock) provides the primary measures of stressor reactivity in this task.
      Predictable and unpredictable startle potentiation are used to calculate overall stressor
      reactivity and selective unpredictable stressor reactivity. Further detail on these
      reactivity measures is provided in the Independent Variables section. Detail on the
      quantification of startle potentiation is provided at the end of this registration.

      Smokers provide three weeks (1 week pre-quit, 2 weeks post-quit) of brief 4x daily, real-time
      web-survey reports of recent cigarette use, NRT use, and other measures not relevant to this
      study's purpose on the participants' smartphones. At two weeks post-quit, smokers are
      scheduled for a laboratory visit where participants provide an additional report via staff
      interview of any smoking during the two-week smoking cessation period.

      The stressor reactivity measures from the NPU task will be tested as predictors of clinical
      outcome (i.e., continuous abstinence during the two-week cessation period) to evaluate the
      validity of each as surrogate endpoints for use in research on stress mechanisms in smoking
      relapse. Deprivation status at the time of the NPU stressor task will be examined as a
      moderator of the effect of stressor reactivity to determine if the surrogate endpoints
      predict clinical outcome generally or only as deprivation increases.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Health Services Research
masking: Single (Participant)
measure: Overall Stressor Reactivity
time frame: up to 24 hours after start of cessation attempt (deprived groups); during normal smoking prior to quit attempt, ie. Baseline (non-deprived groups)
description: The average of unpredictable startle potentiation and predictable startle potentiation during the first administration of the NPU stressor task.
measure: Relative Unpredictable Stressor Reactivity
time frame: up to 24 hours post cessation attempt (deprived groups); during normal smoking prior to quit attempt, ie. Baseline (non-deprived groups)
description: Unpredictable startle potentiation minus predictable startle potentiation during the first administration of the NPU stressor task
measure: Change in Overall Stressor Reactivity
time frame: baseline and up to 14 days post cessation attempt (non-deprived groups); baseline and up to 24 hours post quit attempt (deprived groups)
description: A difference score of overall stressor reactivity during the second administration of the NPU stressor task relative to the first NPU stressor task
measure: Change in Relative Unpredictable Stressor Reactivity
time frame: baseline and up to 14 days post cessation attempt (non-deprived groups); baseline and up to 24 hours post quit attempt (deprived groups)
description: A difference score of relative unpredictable stressor reactivity during the second administration of the NPU stressor task relative to the first NPU stressor task
arm group label: Active Deprived
arm group type: Experimental
description: 21 mg nicotine patches and 2 mg nicotine lozenges
+ First NPU task takes place 24 hours after start of quit attempt
arm group label: Active Non-deprived
arm group type: Experimental
description: 21 mg nicotine patches and 2 mg nicotine lozenges
+ First NPU task takes place during normal smoking prior to quit attempt
arm group label: Placebo Deprived
arm group type: Active Comparator
description: Placebo patches and placebo lozenges
+ First NPU task takes place 24 hours after start of quit attempt
arm group label: Placebo Non-deprived
arm group type: Active Comparator
description: Placebo patches and placebo lozenges
+ First NPU task takes place during normal smoking prior to quit attempt
intervention type: Combination Product
intervention name: nicotine
arm group label: Active Deprived
arm group label: Active Non-deprived
intervention type: Other
intervention name: placebo
arm group label: Placebo Deprived
arm group label: Placebo Non-deprived
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Tobacco Use Disorder
mesh term: Nicotine
sharing ipd: Yes
ipd description: IPD will be shared on the data repository at Open Science Foundation
ipd info type: Study Protocol
ipd info type: Analytic Code
ipd time frame: Data will be available on submission of first manuscript based on study
ipd access criteria: Data are completely open
ipd url: https://osf.io/dz9yu/
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 