<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/NCT01685996</url>
  </required_header>
  <id_info>
    <org_study_id>NA_00074143</org_study_id>
    <secondary_id>R21DA034164</secondary_id>
    <nct_id>NCT01685996</nct_id>
  </id_info>
  <brief_title>Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation</brief_title>
  <acronym>1207</acronym>
  <official_title>Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation</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>
      Randomized trial to evaluate whether zonisamide can enhance varenicline-induced smoking&#xD;
      cessation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      About 20.6 % of the US population smokes cigarettes. This group includes nicotine dependent&#xD;
      smokers who are resistant to current smoking cessation treatments. Varenicline is a smoking&#xD;
      cessation medication found in meta-analytic reviews to be superior to other smoking cessation&#xD;
      treatments, but 56% of patients who take varenicline do not quit. One strategy to increase&#xD;
      quit rates may be to administer a second medication to augment the efficacy of varenicline.&#xD;
      The anti-epileptic medication zonisamide is a good candidate for adjunct treatment as it&#xD;
      increases dopaminergic tone, normalizes glutamate homeostasis, potentiates Gamma-Aminobutyric&#xD;
      Acid (GABA) release. Zonisamide improves sleep and promotes weight loss, two prominent issues&#xD;
      not addressed by varenicline. Finally, the PI of this proposal has documented unpleasant&#xD;
      changes in the taste of cigarettes and reductions in nicotine withdrawal among smokers&#xD;
      receiving zonisamide as part of another clinical trial. The proposed study will explore the&#xD;
      efficacy of varenicline + zonisamide for smoking cessation in a controlled, clinical trial.&#xD;
      Eligible participants (n=60) will be smokers (&gt;10 cig/day for &gt;1 year) seeking treatment.&#xD;
      They will be randomly assigned to receive varenicline + double-blind zonisamide or placebo&#xD;
      for a 10-weeks. Participants will visit the clinic weekly to receive medications and smoking&#xD;
      cessation counseling and to complete self-report questionnaires. Smoking status will be&#xD;
      assessed via weekly urinalysis testing for cotinine (abstinence: &lt;200ng/ml). Cotinine is a&#xD;
      sensitive indicator of smoking status with a longer half-life then carbon monoxide (CO) and&#xD;
      is more likely to detect low or intermittent smoking. The study hypothesis is that&#xD;
      participants who receive the combination zonisamide + varenicline will achieve greater&#xD;
      smoking abstinence compared to varenicline alone. The primary outcome measure will be the&#xD;
      4-week rate of biochemically-confirmed continuous smoking abstinence during weeks 7-10.&#xD;
      Secondary outcomes will include self-reported rates of smoking, subjective effects of&#xD;
      cigarettes, weight change from baseline to week 10, sleep quality, and nicotine withdrawal&#xD;
      severity. This study will advance the science and clinical treatment of smoking cessation,&#xD;
      and will provide the prerequisite data to develop a larger scale clinical trial evaluation of&#xD;
      the combination zonisamide + varenicline for smoking cessation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">May 2014</completion_date>
  <primary_completion_date type="Actual">May 2014</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Participants Abstinent From Smoking During Study Weeks 7-10</measure>
    <time_frame>weeks 7-10</time_frame>
    <description>Biochemically-verified continuous smoking abstinence during weeks 7-10 of the study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Nicotine Withdrawal Symptom Severity</measure>
    <time_frame>Past 24 hours</time_frame>
    <description>Total Score from the Minnesota Nicotine Withdrawal Questionnaire (MNWQ), assessed at weekly visits. The MNWQ is a commonly-used 12-item Likert scale self-report measure of nicotine symptoms. Individual symptoms were rated from 0 (none) to 4 (severe) for each item and the Total score range was 0 - 48. Ratings were collected once weekly during study visits.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">74</enrollment>
  <condition>Nicotine Dependence</condition>
  <arm_group>
    <arm_group_label>zonisamide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>participants will receive zonisamide capsules (up to 300 mg) to take once a day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive placebo capsules to take once a day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>zonisamide</intervention_name>
    <description>In addition to zonisamide vs placebo treatment, varenicline tablets will be dispensed with specific instructions to take at the recommended doses for smoking cessation Participants will receive brief smoking cessation counseling and referral to a quitline</description>
    <arm_group_label>zonisamide</arm_group_label>
    <other_name>zonegran®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ages 18 - 65 years old; smoking &gt; 10 cigarettes per day for &gt; 1 year&#xD;
&#xD;
          -  Desire to quit smoking&#xD;
&#xD;
          -  Provide a cotinine positive urine sample&#xD;
&#xD;
          -  Commitment to come to the clinic once a week for the 10-week study duration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy to varenicline or sulfonamide drugs (e.g., trimethoprim/sulfamethoxazole,&#xD;
             zonisamide or topiramate);&#xD;
&#xD;
          -  Renal insufficiency (eGFR &lt; 60 mL)&#xD;
&#xD;
          -  Renal tubular acidosis&#xD;
&#xD;
          -  History of nephrolithiasis&#xD;
&#xD;
          -  Unexplained hematuria&#xD;
&#xD;
          -  Transaminase elevations &gt; 3 times the Upper Limit of Normal (ULN)&#xD;
&#xD;
          -  BMI &lt; 19&#xD;
&#xD;
          -  Diabetes mellitus&#xD;
&#xD;
          -  Respiratory insufficiency&#xD;
&#xD;
          -  Asthma requiring medication&#xD;
&#xD;
          -  Heart failure&#xD;
&#xD;
          -  Chronic diarrhea predisposing to acidosis&#xD;
&#xD;
          -  Glaucoma, family history of glaucoma, one-sided blindness&#xD;
&#xD;
          -  History of seizures or use of anticonvulsant medications (not including sedatives)&#xD;
&#xD;
          -  HIV infection on HAART medication (or CD4 T cell count &lt; 200 /mL)&#xD;
&#xD;
          -  History of serious psychiatric disorder: psychosis, dementia, depression requiring&#xD;
             medication in last 6 months, suicidal or homicidal ideation, evidence of violent&#xD;
             behavior in the last 6 months.&#xD;
&#xD;
          -  Recent use (last 30 days) of bupropion, nortriptyline, or clonidine&#xD;
&#xD;
          -  Recent use (last 30 days) of Nicotine Replacement Products that would interfere with&#xD;
             urine cotinine testing&#xD;
&#xD;
          -  Use of tobacco products other than cigarettes&#xD;
&#xD;
          -  For female participants, pregnancy, lactation, or refusal to use an effective method&#xD;
             of contraception.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Annie Umbricht, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistant Professor Behavioral Pharmacology Research Unit The Johns Hopkins University School of Medicine 5510 Nathan Shock Drive Baltimore, MD 21224 tel: 410-550-1917 fax:410-550-0011 annieumbricht@jhu.edu</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Behavioral Pharmacology Research Unit</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>September 12, 2012</study_first_submitted>
  <study_first_submitted_qc>September 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 17, 2012</study_first_posted>
  <results_first_submitted>April 17, 2017</results_first_submitted>
  <results_first_submitted_qc>May 30, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">June 5, 2017</results_first_posted>
  <last_update_submitted>January 22, 2018</last_update_submitted>
  <last_update_submitted_qc>January 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 24, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>tobacco</keyword>
  <keyword>smoking cessation</keyword>
  <keyword>nicotine</keyword>
  <keyword>cigarettes</keyword>
  <keyword>nicotine withdrawal</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>Zonisamide</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Zonisamide</title>
          <description>participants will receive zonisamide capsules (up to 300 mg) to take once a day.&#xD;
zonisamide: In addition to zonisamide vs placebo treatment, varenicline tablets will be dispensed with specific instructions to take at the recommended doses for smoking cessation Participants will receive brief smoking cessation counseling and referral to a quitline</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Participants will receive placebo capsules to take once a day&#xD;
placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="40"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Zonisamide</title>
          <description>Participants receive zonisamide + varenicline for smoking cessation</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Participants receive placebo + varenicline for smoking cessation</description>
        </group>
        <group group_id="B3">
          <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="34"/>
            <count group_id="B2" value="40"/>
            <count group_id="B3" value="74"/>
          </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="45.3" spread="9.8"/>
                    <measurement group_id="B2" value="45.9" spread="9.7"/>
                    <measurement group_id="B3" value="45.6" spread="9.8"/>
                  </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="8"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="53"/>
                  </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="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="73"/>
                  </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_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_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_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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="24"/>
                  </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_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_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="34"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Participants Abstinent From Smoking During Study Weeks 7-10</title>
        <description>Biochemically-verified continuous smoking abstinence during weeks 7-10 of the study.</description>
        <time_frame>weeks 7-10</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Zonisamide</title>
            <description>participants will receive zonisamide capsules (up to 300 mg) to take once a day.&#xD;
zonisamide: In addition to zonisamide vs placebo treatment, varenicline tablets will be dispensed with specific instructions to take at the recommended doses for smoking cessation Participants will receive brief smoking cessation counseling and referral to a quitline</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants will receive placebo capsules to take once a day&#xD;
placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Participants Abstinent From Smoking During Study Weeks 7-10</title>
          <description>Biochemically-verified continuous smoking abstinence during weeks 7-10 of the study.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Nicotine Withdrawal Symptom Severity</title>
        <description>Total Score from the Minnesota Nicotine Withdrawal Questionnaire (MNWQ), assessed at weekly visits. The MNWQ is a commonly-used 12-item Likert scale self-report measure of nicotine symptoms. Individual symptoms were rated from 0 (none) to 4 (severe) for each item and the Total score range was 0 - 48. Ratings were collected once weekly during study visits.</description>
        <time_frame>Past 24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Zonisamide</title>
            <description>participants will receive zonisamide capsules (up to 300 mg) to take once a day.&#xD;
zonisamide: In addition to zonisamide vs placebo treatment, varenicline tablets will be dispensed with specific instructions to take at the recommended doses for smoking cessation Participants will receive brief smoking cessation counseling and referral to a quitline</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants will receive placebo capsules to take once a day&#xD;
placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Nicotine Withdrawal Symptom Severity</title>
          <description>Total Score from the Minnesota Nicotine Withdrawal Questionnaire (MNWQ), assessed at weekly visits. The MNWQ is a commonly-used 12-item Likert scale self-report measure of nicotine symptoms. Individual symptoms were rated from 0 (none) to 4 (severe) for each item and the Total score range was 0 - 48. Ratings were collected once weekly during study visits.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Screening Visit</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" spread="6.0"/>
                    <measurement group_id="O2" value="5.6" spread="5.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Admission Visit</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1" spread="5.3"/>
                    <measurement group_id="O2" value="7.0" spread="6.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 1 (pre-quit day)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.3" spread="6."/>
                    <measurement group_id="O2" value="6.2" spread="7.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2 (pre-quit day)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.8" spread="6.0"/>
                    <measurement group_id="O2" value="5.7" spread="6.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3 (target quit day)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7" spread="5.4"/>
                    <measurement group_id="O2" value="6.6" spread="7.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8" spread="5.1"/>
                    <measurement group_id="O2" value="5.9" spread="7.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8" spread="3.7"/>
                    <measurement group_id="O2" value="4.7" spread="5.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.4" spread="4.3"/>
                    <measurement group_id="O2" value="4.0" spread="5.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.8" spread="4.7"/>
                    <measurement group_id="O2" value="4.4" spread="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.7" spread="3.3"/>
                    <measurement group_id="O2" value="4.0" spread="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 9</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.1" spread="3.0"/>
                    <measurement group_id="O2" value="4.1" spread="4.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6" spread="4.9"/>
                    <measurement group_id="O2" value="4.8" spread="5.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected systematically during each study visit for the duration of the 10-week study. All events that were rated as being possibly, probably, or definitely related to study participation are reported. Events can represent nicotine withdrawal symptoms (e.g. all events were documented and nicotine withdrawal symptoms were not excluded from Adverse Events (AE) reporting).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Zonisamide</title>
          <description>participants will receive zonisamide capsules (up to 300 mg) to take once a day.&#xD;
zonisamide: In addition to zonisamide vs placebo treatment, varenicline tablets will be dispensed with specific instructions to take at the recommended doses for smoking cessation Participants will receive brief smoking cessation counseling and referral to a quitline</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants will receive placebo capsules to take once a day&#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="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="14" subjects_affected="11" subjects_at_risk="34"/>
                <counts group_id="E2" events="14" subjects_affected="11" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Sore Throat</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="34"/>
                <counts group_id="E2" events="6" subjects_affected="4" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Chemistry Abnormal</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Jaw Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Pain Lower Extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Adjustment Disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Difficulty Concentrating</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Dream Abnormal</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="34"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Drowsiness</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="34"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="34"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="34"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Paranoid</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Change in Mental Status</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin Rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Pruritis (itching)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Sweating Increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Hot Flashes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Itching Eyes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Pain- Eye</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Annie Umbricht, M.D.</name_or_title>
      <organization>Johns Hopkins University School of Medicine</organization>
      <phone>410-550-1917</phone>
      <email>annieumbricht@jhu.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/NCT01685996
org study id: NA_00074143
secondary id: R21DA034164
nct id: NCT01685996
lead sponsor: 
collaborator: 
has dmc: Yes
Randomized trial to evaluate whether zonisamide can enhance varenicline-induced smoking
      cessation.
About 20.6 % of the US population smokes cigarettes. This group includes nicotine dependent
      smokers who are resistant to current smoking cessation treatments. Varenicline is a smoking
      cessation medication found in meta-analytic reviews to be superior to other smoking cessation
      treatments, but 56% of patients who take varenicline do not quit. One strategy to increase
      quit rates may be to administer a second medication to augment the efficacy of varenicline.
      The anti-epileptic medication zonisamide is a good candidate for adjunct treatment as it
      increases dopaminergic tone, normalizes glutamate homeostasis, potentiates Gamma-Aminobutyric
      Acid (GABA) release. Zonisamide improves sleep and promotes weight loss, two prominent issues
      not addressed by varenicline. Finally, the PI of this proposal has documented unpleasant
      changes in the taste of cigarettes and reductions in nicotine withdrawal among smokers
      receiving zonisamide as part of another clinical trial. The proposed study will explore the
      efficacy of varenicline + zonisamide for smoking cessation in a controlled, clinical trial.
      Eligible participants (n=60) will be smokers (>10 cig/day for >1 year) seeking treatment.
      They will be randomly assigned to receive varenicline + double-blind zonisamide or placebo
      for a 10-weeks. Participants will visit the clinic weekly to receive medications and smoking
      cessation counseling and to complete self-report questionnaires. Smoking status will be
      assessed via weekly urinalysis testing for cotinine (abstinence: <200ng/ml). Cotinine is a
      sensitive indicator of smoking status with a longer half-life then carbon monoxide (CO) and
      is more likely to detect low or intermittent smoking. The study hypothesis is that
      participants who receive the combination zonisamide + varenicline will achieve greater
      smoking abstinence compared to varenicline alone. The primary outcome measure will be the
      4-week rate of biochemically-confirmed continuous smoking abstinence during weeks 7-10.
      Secondary outcomes will include self-reported rates of smoking, subjective effects of
      cigarettes, weight change from baseline to week 10, sleep quality, and nicotine withdrawal
      severity. This study will advance the science and clinical treatment of smoking cessation,
      and will provide the prerequisite data to develop a larger scale clinical trial evaluation of
      the combination zonisamide + varenicline for smoking cessation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Percent Participants Abstinent From Smoking During Study Weeks 7-10
time frame: weeks 7-10
description: Biochemically-verified continuous smoking abstinence during weeks 7-10 of the study.
measure: Nicotine Withdrawal Symptom Severity
time frame: Past 24 hours
description: Total Score from the Minnesota Nicotine Withdrawal Questionnaire (MNWQ), assessed at weekly visits. The MNWQ is a commonly-used 12-item Likert scale self-report measure of nicotine symptoms. Individual symptoms were rated from 0 (none) to 4 (severe) for each item and the Total score range was 0 - 48. Ratings were collected once weekly during study visits.
arm group label: zonisamide
arm group type: Experimental
description: participants will receive zonisamide capsules (up to 300 mg) to take once a day.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will receive placebo capsules to take once a day
intervention type: Drug
intervention name: zonisamide
description: In addition to zonisamide vs placebo treatment, varenicline tablets will be dispensed with specific instructions to take at the recommended doses for smoking cessation Participants will receive brief smoking cessation counseling and referral to a quitline
arm group label: zonisamide
other name: zonegran®
intervention type: Drug
intervention name: placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Annie Umbricht, M.D.
role: Principal Investigator
affiliation: Assistant Professor Behavioral Pharmacology Research Unit The Johns Hopkins University School of Medicine 5510 Nathan Shock Drive Baltimore, MD 21224 tel: 410-550-1917 fax:410-550-0011 annieumbricht@jhu.edu
facility: 
country: United States
responsible party type: Sponsor
mesh term: Tobacco Use Disorder
mesh term: Zonisamide
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 