<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/NCT01664741</url>
  </required_header>
  <id_info>
    <org_study_id>NA_00036996</org_study_id>
    <secondary_id>R01DA026823</secondary_id>
    <nct_id>NCT01664741</nct_id>
  </id_info>
  <brief_title>Nicotine Dependence, Withdrawal and Replacement Therapy Assessed by PET Imaging</brief_title>
  <official_title>Nicotine Dependence, Withdrawal and Replacement Therapy Assessed by PET Imaging</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The proposed research will provide significant new gender-specific information of scientific&#xD;
      and clinical relevance on the function of the mu-opioid system in nicotine dependence and&#xD;
      therapeutic effectiveness of nicotine replacement therapy (NRT). The studies will help to&#xD;
      explain the differences in the prevalence of smoking in men and women, sex-specific&#xD;
      differences in nicotine craving and withdrawal as well as the poorer therapeutic response to&#xD;
      NRT. This work may pave the way to the design of improved pharmacotherapies that can more&#xD;
      effectively target the endogenous opioid system in the treatment of nicotine dependence.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      While smoking prevalence has declined for both men and women over the last two decades, rates&#xD;
      among women have shown a much shallower decrease and, in recent years, prevalence of&#xD;
      cigarette initiation has been higher for girls than boys. Smoking among women of&#xD;
      child-bearing age has significant negative health consequences for mother and child,&#xD;
      increasing fetal and infant morbidity and mortality. Women are both less likely to initiate a&#xD;
      quit attempt and more likely to relapse if these women do quit. Nicotine replacement therapy&#xD;
      (NRT), still the most widely used smoking treatment intervention in the United States, is&#xD;
      less effective for women compared with men, and women report less craving reduction on NRT.&#xD;
      The endogenous opioid system is involved in smoking initiation, nicotine craving and reward&#xD;
      as well as nicotine withdrawal symptoms. Interestingly, research suggests that sexual&#xD;
      dimorphic features of the endogenous mu-opioid system may in part explain gender differences&#xD;
      in nicotine effects. To better understand the role of the mu-opioid system in poorer NRT&#xD;
      responses in women, this proposal will examine NRT effects on mu opioid receptor binding&#xD;
      potential (MOR BP) in female compared to male smokers during active versus placebo NRT.&#xD;
      Specifically, nicotine dependent women and men in active smoking status will undergo PET&#xD;
      imaging for MOR BP measurement using 11C-carfentanil. Following baseline PET measurement in&#xD;
      active smoking (scan 1), smokers will be randomized to active or placebo nicotine replacement&#xD;
      therapy ((A-NRT or P-NRT); 72 hours later, a second scan will be obtained. As a reference&#xD;
      group, demographically-matched women and men who have never smoked will undergo two scans as&#xD;
      well. Behavioral measurements of nicotine reward, craving and withdrawal will be obtained&#xD;
      repeatedly across the protocol. The proposed research will provide significant new,&#xD;
      gender-specific information of scientific and clinical relevance on the function of the&#xD;
      mu-opioid system in nicotine dependence and therapeutic effectiveness of nicotine replacement&#xD;
      therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 2012</start_date>
  <completion_date type="Actual">December 2018</completion_date>
  <primary_completion_date type="Actual">May 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>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Mu-opioid Receptor Binding Potential (BP) Between Baseline and Post-patch Scans</measure>
    <time_frame>90 minutes</time_frame>
    <description>BP provides an estimate of the product of the density of available receptors (Bmax' or the receptor density Bmax less those occupied by endogenous transmitters) and the affinity [1/equilibrium dissociation constant (KD)]. We use reference tissue graphical analysis (RTGA) to obtain regional BP values using occipital lobe as a reference region. Negative BP change means means a decrease in the BP and positive BP change means an increase in the BP.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Relationship Between Change in Mu-opioid Receptor Binding Potential and Visual Analog Craving Scale Score</measure>
    <time_frame>72 hours</time_frame>
    <description>Regression measure (β) between change in mu-opioid receptor binding potential between baseline scan and post-treatment scan in the left amygdala and mean Craving Visual Analog Scale score on Days 2 - 4 of the Clinical Research Unit stay. Craving visual analog scale ranges from 0 (not at all) to 20 (worst ever).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relationship Between Change in Mu-opioid Receptor Binding Potential and Minnesota Nicotine Withdrawal Scale Score</measure>
    <time_frame>72 hours</time_frame>
    <description>Regression measure (β) between change in mu-opioid receptor binding potential between baseline scan and post-treatment scan and mean Minnesota Nicotine Withdrawal Scale (MNWS) score on Days 2 - 4 of the Clinical Research Unit stay. The MNWS is a self-report measure that consists of 14 nicotine withdrawal symptoms each rated on a 0 - 4 response scale for severity over the past 24 hours. Higher scores are indicative of greater nicotine withdrawal severity.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">127</enrollment>
  <condition>Nicotine Dependence</condition>
  <arm_group>
    <arm_group_label>Nicotine patch - transdermal</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>21 mg nicotine patch</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo NRT</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching placebo patch</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy non-smoker comparison</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Demographically-matched women and men who have never smoked</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nicotine patch - transdermal</intervention_name>
    <description>21 mg patch</description>
    <arm_group_label>Nicotine patch - transdermal</arm_group_label>
    <other_name>Nicotine Replacement Therapy (NRT)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <arm_group_label>Placebo NRT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  21 - 60 years old&#xD;
&#xD;
          -  must meet DSM-IV criteria for nicotine dependence and be actively smoking&#xD;
&#xD;
        Exclusion Criteria: subjects must meet study guidelines for medical and mental health&#xD;
        status.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mary E McCaul, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Johns Hopkins University School of Medicine</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</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 10, 2012</study_first_submitted>
  <study_first_submitted_qc>August 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 14, 2012</study_first_posted>
  <results_first_submitted>March 27, 2019</results_first_submitted>
  <results_first_submitted_qc>April 18, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">May 9, 2019</results_first_posted>
  <last_update_submitted>April 18, 2019</last_update_submitted>
  <last_update_submitted_qc>April 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Nicotine dependence</keyword>
  <keyword>cigarette</keyword>
  <keyword>smoking</keyword>
  <keyword>nicotine replacement therapy</keyword>
  <keyword>positron emission tomography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tobacco Use Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nicotine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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>October 19, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/41/NCT01664741/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>102 of the participants who passed the on-phone screen came in and signed the consent form to be enrolled in the study. Baseline characteristics data was collected from them but they however failed an assessment done prior to getting the PET scan and so could not start the study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Nicotine Patch - Transdermal</title>
          <description>21 mg nicotine patch&#xD;
Nicotine patch - transdermal</description>
        </group>
        <group group_id="P2">
          <title>Placebo NRT</title>
          <description>Matching placebo patch&#xD;
placebo</description>
        </group>
        <group group_id="P3">
          <title>Healthy Non-smoker Comparison</title>
          <description>Demographically-matched women and men who have never smoked</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>102 of the participants who passed the on-phone screen came in and signed the consent form to be enrolled in the study. Baseline characteristics data was collected from them but they however failed an assessment done prior to getting the PET scan and so could not start the study.</population>
      <group_list>
        <group group_id="B1">
          <title>Nicotine Patch - Transdermal</title>
          <description>21 mg nicotine patch&#xD;
Nicotine patch - transdermal</description>
        </group>
        <group group_id="B2">
          <title>Placebo NRT</title>
          <description>Matching placebo patch&#xD;
placebo</description>
        </group>
        <group group_id="B3">
          <title>Healthy Non-smoker Comparison</title>
          <description>Demographically-matched women and men who have never smoked</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="42"/>
            <count group_id="B2" value="42"/>
            <count group_id="B3" value="43"/>
            <count group_id="B4" value="127"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="43"/>
                    <measurement group_id="B4" value="127"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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_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="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="18"/>
                    <measurement group_id="B4" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="25"/>
                    <measurement group_id="B4" value="79"/>
                  </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="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="42"/>
                    <measurement group_id="B4" value="117"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="4"/>
                  </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="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</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_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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="18"/>
                    <measurement group_id="B4" value="52"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="25"/>
                    <measurement group_id="B4" value="73"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="43"/>
                    <measurement group_id="B4" value="127"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Years of regular smoking</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22.2" spread="12.8"/>
                    <measurement group_id="B2" value="22.2" spread="12.8"/>
                    <measurement group_id="B3" value="0" spread="0"/>
                    <measurement group_id="B4" value="22.2" spread="12.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cigarettes per day</title>
          <units>number of cigarettes/day</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17.0" spread="6.9"/>
                    <measurement group_id="B2" value="17.0" spread="6.9"/>
                    <measurement group_id="B3" value="0" spread="0"/>
                    <measurement group_id="B4" value="17.0" spread="6.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Mu-opioid Receptor Binding Potential (BP) Between Baseline and Post-patch Scans</title>
        <description>BP provides an estimate of the product of the density of available receptors (Bmax' or the receptor density Bmax less those occupied by endogenous transmitters) and the affinity [1/equilibrium dissociation constant (KD)]. We use reference tissue graphical analysis (RTGA) to obtain regional BP values using occipital lobe as a reference region. Negative BP change means means a decrease in the BP and positive BP change means an increase in the BP.</description>
        <time_frame>90 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Nicotine Patch - Transdermal</title>
            <description>21 mg nicotine patch&#xD;
Nicotine patch - transdermal</description>
          </group>
          <group group_id="O2">
            <title>Placebo NRT</title>
            <description>Matching placebo patch&#xD;
placebo</description>
          </group>
          <group group_id="O3">
            <title>Healthy Non-smoker Comparison</title>
            <description>Demographically-matched women and men who have never smoked</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mu-opioid Receptor Binding Potential (BP) Between Baseline and Post-patch Scans</title>
          <description>BP provides an estimate of the product of the density of available receptors (Bmax' or the receptor density Bmax less those occupied by endogenous transmitters) and the affinity [1/equilibrium dissociation constant (KD)]. We use reference tissue graphical analysis (RTGA) to obtain regional BP values using occipital lobe as a reference region. Negative BP change means means a decrease in the BP and positive BP change means an increase in the BP.</description>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>BP Change - Left Amygdala</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.47" spread="3.91"/>
                    <measurement group_id="O2" value="-5.94" spread="3.91"/>
                    <measurement group_id="O3" value="5.60" spread="2.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BP Change - Ventral Striatum</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.24" spread="3.50"/>
                    <measurement group_id="O2" value="-9.25" spread="3.50"/>
                    <measurement group_id="O3" value="0.59" spread="2.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Relationship Between Change in Mu-opioid Receptor Binding Potential and Visual Analog Craving Scale Score</title>
        <description>Regression measure (β) between change in mu-opioid receptor binding potential between baseline scan and post-treatment scan in the left amygdala and mean Craving Visual Analog Scale score on Days 2 - 4 of the Clinical Research Unit stay. Craving visual analog scale ranges from 0 (not at all) to 20 (worst ever).</description>
        <time_frame>72 hours</time_frame>
        <population>This assessment was not done on the healthy non-smokers because they didn't have any nicotine craving.</population>
        <group_list>
          <group group_id="O1">
            <title>Nicotine Patch - Transdermal</title>
            <description>21 mg nicotine patch&#xD;
Nicotine patch - transdermal</description>
          </group>
          <group group_id="O2">
            <title>Placebo NRT</title>
            <description>Matching placebo patch&#xD;
placebo</description>
          </group>
          <group group_id="O3">
            <title>Healthy Non-smoker Comparison</title>
            <description>Demographically-matched women and men who have never smoked</description>
          </group>
        </group_list>
        <measure>
          <title>Relationship Between Change in Mu-opioid Receptor Binding Potential and Visual Analog Craving Scale Score</title>
          <description>Regression measure (β) between change in mu-opioid receptor binding potential between baseline scan and post-treatment scan in the left amygdala and mean Craving Visual Analog Scale score on Days 2 - 4 of the Clinical Research Unit stay. Craving visual analog scale ranges from 0 (not at all) to 20 (worst ever).</description>
          <population>This assessment was not done on the healthy non-smokers because they didn't have any nicotine craving.</population>
          <units>unitless</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.556"/>
                    <measurement group_id="O2" value="-0.550"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Relationship Between Change in Mu-opioid Receptor Binding Potential and Minnesota Nicotine Withdrawal Scale Score</title>
        <description>Regression measure (β) between change in mu-opioid receptor binding potential between baseline scan and post-treatment scan and mean Minnesota Nicotine Withdrawal Scale (MNWS) score on Days 2 - 4 of the Clinical Research Unit stay. The MNWS is a self-report measure that consists of 14 nicotine withdrawal symptoms each rated on a 0 - 4 response scale for severity over the past 24 hours. Higher scores are indicative of greater nicotine withdrawal severity.</description>
        <time_frame>72 hours</time_frame>
        <population>This assessment was not done on the healthy non-smokers because they didn't have any nicotine craving.</population>
        <group_list>
          <group group_id="O1">
            <title>Nicotine Patch - Transdermal</title>
            <description>21 mg nicotine patch&#xD;
Nicotine patch - transdermal</description>
          </group>
          <group group_id="O2">
            <title>Placebo NRT</title>
            <description>Matching placebo patch&#xD;
placebo</description>
          </group>
          <group group_id="O3">
            <title>Healthy Non-smoker Comparison</title>
            <description>Demographically-matched women and men who have never smoked</description>
          </group>
        </group_list>
        <measure>
          <title>Relationship Between Change in Mu-opioid Receptor Binding Potential and Minnesota Nicotine Withdrawal Scale Score</title>
          <description>Regression measure (β) between change in mu-opioid receptor binding potential between baseline scan and post-treatment scan and mean Minnesota Nicotine Withdrawal Scale (MNWS) score on Days 2 - 4 of the Clinical Research Unit stay. The MNWS is a self-report measure that consists of 14 nicotine withdrawal symptoms each rated on a 0 - 4 response scale for severity over the past 24 hours. Higher scores are indicative of greater nicotine withdrawal severity.</description>
          <population>This assessment was not done on the healthy non-smokers because they didn't have any nicotine craving.</population>
          <units>unitless</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Left Amygdala</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.087"/>
                    <measurement group_id="O2" value="-0.836"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ventral Striatum</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.419"/>
                    <measurement group_id="O2" value="-0.794"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>During 4 day Clinical Research Unit stay</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Nicotine Patch - Transdermal</title>
          <description>21 mg nicotine patch&#xD;
Nicotine patch - transdermal</description>
        </group>
        <group group_id="E2">
          <title>Placebo NRT</title>
          <description>Matching placebo patch&#xD;
placebo</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="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </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="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </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>Mary E McCaul</name_or_title>
      <organization>Johns Hopkins School of Medicine</organization>
      <phone>410-955-9526</phone>
      <email>mmccaul1@jhmi.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/NCT01664741
org study id: NA_00036996
secondary id: R01DA026823
nct id: NCT01664741
lead sponsor: 
collaborator: 
has dmc: Yes
The proposed research will provide significant new gender-specific information of scientific
      and clinical relevance on the function of the mu-opioid system in nicotine dependence and
      therapeutic effectiveness of nicotine replacement therapy (NRT). The studies will help to
      explain the differences in the prevalence of smoking in men and women, sex-specific
      differences in nicotine craving and withdrawal as well as the poorer therapeutic response to
      NRT. This work may pave the way to the design of improved pharmacotherapies that can more
      effectively target the endogenous opioid system in the treatment of nicotine dependence.
While smoking prevalence has declined for both men and women over the last two decades, rates
      among women have shown a much shallower decrease and, in recent years, prevalence of
      cigarette initiation has been higher for girls than boys. Smoking among women of
      child-bearing age has significant negative health consequences for mother and child,
      increasing fetal and infant morbidity and mortality. Women are both less likely to initiate a
      quit attempt and more likely to relapse if these women do quit. Nicotine replacement therapy
      (NRT), still the most widely used smoking treatment intervention in the United States, is
      less effective for women compared with men, and women report less craving reduction on NRT.
      The endogenous opioid system is involved in smoking initiation, nicotine craving and reward
      as well as nicotine withdrawal symptoms. Interestingly, research suggests that sexual
      dimorphic features of the endogenous mu-opioid system may in part explain gender differences
      in nicotine effects. To better understand the role of the mu-opioid system in poorer NRT
      responses in women, this proposal will examine NRT effects on mu opioid receptor binding
      potential (MOR BP) in female compared to male smokers during active versus placebo NRT.
      Specifically, nicotine dependent women and men in active smoking status will undergo PET
      imaging for MOR BP measurement using 11C-carfentanil. Following baseline PET measurement in
      active smoking (scan 1), smokers will be randomized to active or placebo nicotine replacement
      therapy ((A-NRT or P-NRT); 72 hours later, a second scan will be obtained. As a reference
      group, demographically-matched women and men who have never smoked will undergo two scans as
      well. Behavioral measurements of nicotine reward, craving and withdrawal will be obtained
      repeatedly across the protocol. The proposed research will provide significant new,
      gender-specific information of scientific and clinical relevance on the function of the
      mu-opioid system in nicotine dependence and therapeutic effectiveness of nicotine replacement
      therapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in Mu-opioid Receptor Binding Potential (BP) Between Baseline and Post-patch Scans
time frame: 90 minutes
description: BP provides an estimate of the product of the density of available receptors (Bmax' or the receptor density Bmax less those occupied by endogenous transmitters) and the affinity [1/equilibrium dissociation constant (KD)]. We use reference tissue graphical analysis (RTGA) to obtain regional BP values using occipital lobe as a reference region. Negative BP change means means a decrease in the BP and positive BP change means an increase in the BP.
measure: Relationship Between Change in Mu-opioid Receptor Binding Potential and Visual Analog Craving Scale Score
time frame: 72 hours
description: Regression measure (β) between change in mu-opioid receptor binding potential between baseline scan and post-treatment scan in the left amygdala and mean Craving Visual Analog Scale score on Days 2 - 4 of the Clinical Research Unit stay. Craving visual analog scale ranges from 0 (not at all) to 20 (worst ever).
measure: Relationship Between Change in Mu-opioid Receptor Binding Potential and Minnesota Nicotine Withdrawal Scale Score
time frame: 72 hours
description: Regression measure (β) between change in mu-opioid receptor binding potential between baseline scan and post-treatment scan and mean Minnesota Nicotine Withdrawal Scale (MNWS) score on Days 2 - 4 of the Clinical Research Unit stay. The MNWS is a self-report measure that consists of 14 nicotine withdrawal symptoms each rated on a 0 - 4 response scale for severity over the past 24 hours. Higher scores are indicative of greater nicotine withdrawal severity.
arm group label: Nicotine patch - transdermal
arm group type: Active Comparator
description: 21 mg nicotine patch
arm group label: Placebo NRT
arm group type: Placebo Comparator
description: Matching placebo patch
arm group label: Healthy non-smoker comparison
arm group type: No Intervention
description: Demographically-matched women and men who have never smoked
intervention type: Drug
intervention name: Nicotine patch - transdermal
description: 21 mg patch
arm group label: Nicotine patch - transdermal
other name: Nicotine Replacement Therapy (NRT)
intervention type: Drug
intervention name: placebo
arm group label: Placebo NRT
criteria: 
gender: All
minimum age: 21 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mary E McCaul, Ph.D.
role: Principal Investigator
affiliation: Johns Hopkins University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Tobacco Use Disorder
mesh term: Nicotine
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 