<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/NCT02185131</url>
  </required_header>
  <id_info>
    <org_study_id>R21AA022123</org_study_id>
    <secondary_id>5R21AA022123-02</secondary_id>
    <nct_id>NCT02185131</nct_id>
  </id_info>
  <brief_title>Double-blind Pilot Trial of Mirtazapine for the Treatment of Co-occurring AD/MDD.</brief_title>
  <acronym>PT-MAD</acronym>
  <official_title>Double-blind Pilot Trial of Mirtazapine for the Treatment of Co-occurring AD/MDD.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Mirtazapine is a non-SSRI (selective serotonin reuptake inhibitor) medication with a unique&#xD;
      structure and mechanism of action. Recent study results suggest that mirtazapine may be more&#xD;
      effective and faster acting than other antidepressants. Levels of alcohol use have been shown&#xD;
      to be associated with levels of depressive symptoms among comorbid populations. Our own&#xD;
      recent open label pilot study suggested robust within-group efficacy for mirtazapine for&#xD;
      decreasing both the drinking and the depressive symptoms of persons with co-occurring alcohol&#xD;
      dependence/major depressive disorder (AD/MDD). However, no placebo control group was employed&#xD;
      in that study, so between-group efficacy versus placebo could not be assessed. The current&#xD;
      grant submission proposes to conduct a first double-blind, placebo-controlled study to&#xD;
      evaluate the efficacy of mirtazapine versus placebo for decreasing the alcohol use and&#xD;
      depressive symptoms of persons with comorbid AD/MDD. If the results of this proposed&#xD;
      double-blind pilot trial are promising, then the effect sizes found in this proposed study&#xD;
      will be used to help design an adequately-powered R01 treatment trial to definitively test&#xD;
      the efficacy of mirtazapine in this comorbid population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Alcohol dependence (AD) and Major Depressive Disorder (MDD) are among the most frequent&#xD;
      psychiatric disorders in the general population, and the co-occurrence of those disorders&#xD;
      represents a significant public health problem. Levels of alcohol use have been shown to be&#xD;
      associated with levels of depressive symptoms among comorbid populations. Previous medication&#xD;
      trials with SSRI antidepressants in this comorbid population have produced disappointing&#xD;
      results. Mirtazapine is a non-SSRI medication with a unique structure and mechanism of&#xD;
      action. Recent study results suggest that mirtazapine may be more effective and faster acting&#xD;
      than other antidepressants. Our own recent open label pilot study suggested robust&#xD;
      within-group efficacy for mirtazapine for decreasing both the drinking and the depressive&#xD;
      symptoms of AD/MDD subjects. However, no placebo control group was employed in that study, so&#xD;
      between-group efficacy versus placebo could not be assessed. The current grant submission&#xD;
      proposes to conduct a first double-blind, placebo-controlled pilot study to provide a&#xD;
      preliminary assessment of the efficacy of mirtazapine versus placebo for decreasing the&#xD;
      alcohol use and depressive symptoms of persons with comorbid AD/MDD. If the results of this&#xD;
      proposed double-blind pilot study are promising, then the effect sizes found in this proposed&#xD;
      study will be used to help design an adequately-powered R01 treatment trial to definitively&#xD;
      test the efficacy of mirtazapine versus placebo in this comorbid population.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2013</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">July 2016</primary_completion_date>
  <phase>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>Drinks Per Drinking Day</measure>
    <time_frame>12 Weeks</time_frame>
    <description>Level of drinking, as indicated by the number of drinks per day as recorded on the Timeline Follow-Back calendar.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Level of Depressive Symptoms</measure>
    <time_frame>12 Weeks</time_frame>
    <description>Level of depressive symptoms, as indicated by the score on the Beck Depression Inventory. The Beck Depression Inventory II scoring range is as follows: 0-13 minimal depressive symptoms, 14-19 mild depressive symptoms, 20-28 moderate depressive symptoms and 29-63 severe depressive symptoms.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Major Depressive Disorder</condition>
  <condition>Alcohol Use Disorder</condition>
  <arm_group>
    <arm_group_label>Mirtazapine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mirtazapine</intervention_name>
    <description>Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.</description>
    <arm_group_label>Mirtazapine</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Remeron</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.</description>
    <arm_group_label>Mirtazapine</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  DSM-IV-TR diagnosis of current alcohol dependence, confirmed by the Mini International&#xD;
             Neuropsychiatric Interview (MINI)&#xD;
&#xD;
          -  DSM-IV-TR diagnosis of current major depressive disorder, confirmed by the Mini&#xD;
             International Neuropsychiatric Interview (MINI)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any person who meets criteria for alcohol-induced depression&#xD;
&#xD;
          -  Any psychotic disorder bipolar disorder, mental retardation, impaired cognitive&#xD;
             functioning, or use of any psychotropic medication in the previous month&#xD;
&#xD;
          -  Current Diagnostic and Statistical Manual (DSM-IV) criteria for dependence on&#xD;
             substances other than alcohol, cannabis, nicotine, or caffeine&#xD;
&#xD;
          -  Significant neurological conditions or medical conditions&#xD;
&#xD;
          -  Persistent elevation of liver function enzymes indicating active liver disease&#xD;
             (elevated t. bilirubin or elevation to three-time normal range of liver enzymes, SGOT,&#xD;
             SGPT, or g-GTP)&#xD;
&#xD;
          -  The presence of renal function impairment defined as serum creatinine &gt;2x upper limit&#xD;
             of normal&#xD;
&#xD;
          -  Pregnancy, inability or unwillingness to use contraceptive methods&#xD;
&#xD;
          -  Use of any antidepressant medication in the prior two months, or any lifetime use of&#xD;
             mirtazapine&#xD;
&#xD;
          -  Inability to read or understand study forms and agree to informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jack R Cornelius, M.D., M.P.H.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Western Psychiatric Institute and Clinic</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Cornelius JR, Douaihy AB, Clark DB, Chung T, Wood DS, Daley D. Mirtazapine in Comorbid Major Depression and Alcohol Dependence: An Open-Label Trial. J Dual Diagn. 2012 Sep 1;8(3):200-204. doi: 10.1080/15504263.2012.696527. Epub 2012 Aug 8.</citation>
    <PMID>23230395</PMID>
  </reference>
  <reference>
    <citation>Cornelius JR, Chung T, Douaihy AB, Kirisci L, Glance J, Kmiec J, FitzGerald D, Wesesky MA, Salloum I. Mirtazapine in comorbid major depression and an alcohol use disorder: A double-blind placebo-controlled pilot trial. Psychiatry Res. 2016 Aug 30;242:326-330. doi: 10.1016/j.psychres.2016.06.005. Epub 2016 Jun 15.</citation>
    <PMID>27327217</PMID>
  </reference>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>June 26, 2014</study_first_submitted>
  <study_first_submitted_qc>July 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 2014</study_first_posted>
  <results_first_submitted>August 17, 2016</results_first_submitted>
  <results_first_submitted_qc>March 24, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 5, 2017</results_first_posted>
  <last_update_submitted>March 24, 2017</last_update_submitted>
  <last_update_submitted_qc>March 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Jack Cornelius</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Major Depressive Disorder</keyword>
  <keyword>Alcohol Use Disorder</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
    <mesh_term>Alcohol Drinking</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mirtazapine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No individual subject data will be shared.</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Mirtazapine</title>
          <description>Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.&#xD;
Mirtazapine: Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.&#xD;
Placebo: Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.&#xD;
Mirtazapine: Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.&#xD;
Placebo: Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Mirtazapine</title>
          <description>Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.&#xD;
Mirtazapine: Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.&#xD;
Placebo: Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.&#xD;
Mirtazapine: Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.&#xD;
Placebo: Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.</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="7"/>
            <count group_id="B2" value="9"/>
            <count group_id="B3" value="16"/>
          </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="45.2" spread="5.9"/>
                    <measurement group_id="B2" value="37.4" spread="9.8"/>
                    <measurement group_id="B3" value="41.3" spread="8.8"/>
                  </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="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Drinks Per Drinking Day</title>
        <description>Level of drinking, as indicated by the number of drinks per day as recorded on the Timeline Follow-Back calendar.</description>
        <time_frame>12 Weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Mirtazapine</title>
            <description>Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.&#xD;
Mirtazapine: Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.&#xD;
Placebo: Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.&#xD;
Mirtazapine: Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.&#xD;
Placebo: Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.</description>
          </group>
        </group_list>
        <measure>
          <title>Drinks Per Drinking Day</title>
          <description>Level of drinking, as indicated by the number of drinks per day as recorded on the Timeline Follow-Back calendar.</description>
          <units>Drinks per drinking day</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" spread="1.6"/>
                    <measurement group_id="O2" value="4.4" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Level of Depressive Symptoms</title>
        <description>Level of depressive symptoms, as indicated by the score on the Beck Depression Inventory. The Beck Depression Inventory II scoring range is as follows: 0-13 minimal depressive symptoms, 14-19 mild depressive symptoms, 20-28 moderate depressive symptoms and 29-63 severe depressive symptoms.</description>
        <time_frame>12 Weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Mirtazapine</title>
            <description>Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.&#xD;
Mirtazapine: Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.&#xD;
Placebo: Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.&#xD;
Mirtazapine: Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.&#xD;
Placebo: Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Depressive Symptoms</title>
          <description>Level of depressive symptoms, as indicated by the score on the Beck Depression Inventory. The Beck Depression Inventory II scoring range is as follows: 0-13 minimal depressive symptoms, 14-19 mild depressive symptoms, 20-28 moderate depressive symptoms and 29-63 severe depressive symptoms.</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="6"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.6" spread="7.7"/>
                    <measurement group_id="O2" value="26.1" spread="11.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected from Baseline Visit through Week 12.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Mirtazapine</title>
          <description>Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.&#xD;
Mirtazapine: Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.&#xD;
Placebo: Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.&#xD;
Mirtazapine: Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.&#xD;
Placebo: Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <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="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
              </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>Jack R. Cornelius, M.D., M.P.H.</name_or_title>
      <organization>University of Pittsburgh</organization>
      <phone>412-246-5149</phone>
      <email>corneliusjr@upmc.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/NCT02185131
org study id: R21AA022123
secondary id: 5R21AA022123-02
nct id: NCT02185131
lead sponsor: 
collaborator: 
has dmc: No
Mirtazapine is a non-SSRI (selective serotonin reuptake inhibitor) medication with a unique
      structure and mechanism of action. Recent study results suggest that mirtazapine may be more
      effective and faster acting than other antidepressants. Levels of alcohol use have been shown
      to be associated with levels of depressive symptoms among comorbid populations. Our own
      recent open label pilot study suggested robust within-group efficacy for mirtazapine for
      decreasing both the drinking and the depressive symptoms of persons with co-occurring alcohol
      dependence/major depressive disorder (AD/MDD). However, no placebo control group was employed
      in that study, so between-group efficacy versus placebo could not be assessed. The current
      grant submission proposes to conduct a first double-blind, placebo-controlled study to
      evaluate the efficacy of mirtazapine versus placebo for decreasing the alcohol use and
      depressive symptoms of persons with comorbid AD/MDD. If the results of this proposed
      double-blind pilot trial are promising, then the effect sizes found in this proposed study
      will be used to help design an adequately-powered R01 treatment trial to definitively test
      the efficacy of mirtazapine in this comorbid population.
Alcohol dependence (AD) and Major Depressive Disorder (MDD) are among the most frequent
      psychiatric disorders in the general population, and the co-occurrence of those disorders
      represents a significant public health problem. Levels of alcohol use have been shown to be
      associated with levels of depressive symptoms among comorbid populations. Previous medication
      trials with SSRI antidepressants in this comorbid population have produced disappointing
      results. Mirtazapine is a non-SSRI medication with a unique structure and mechanism of
      action. Recent study results suggest that mirtazapine may be more effective and faster acting
      than other antidepressants. Our own recent open label pilot study suggested robust
      within-group efficacy for mirtazapine for decreasing both the drinking and the depressive
      symptoms of AD/MDD subjects. However, no placebo control group was employed in that study, so
      between-group efficacy versus placebo could not be assessed. The current grant submission
      proposes to conduct a first double-blind, placebo-controlled pilot study to provide a
      preliminary assessment of the efficacy of mirtazapine versus placebo for decreasing the
      alcohol use and depressive symptoms of persons with comorbid AD/MDD. If the results of this
      proposed double-blind pilot study are promising, then the effect sizes found in this proposed
      study will be used to help design an adequately-powered R01 treatment trial to definitively
      test the efficacy of mirtazapine versus placebo in this comorbid population.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Drinks Per Drinking Day
time frame: 12 Weeks
description: Level of drinking, as indicated by the number of drinks per day as recorded on the Timeline Follow-Back calendar.
measure: Level of Depressive Symptoms
time frame: 12 Weeks
description: Level of depressive symptoms, as indicated by the score on the Beck Depression Inventory. The Beck Depression Inventory II scoring range is as follows: 0-13 minimal depressive symptoms, 14-19 mild depressive symptoms, 20-28 moderate depressive symptoms and 29-63 severe depressive symptoms.
arm group label: Mirtazapine
arm group type: Active Comparator
description: Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.
arm group label: Placebo
arm group type: Active Comparator
description: Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.
intervention type: Drug
intervention name: Mirtazapine
description: Gelatin capsules mirtazapine 15 mg, 1 capsule every a.m. Medication will be increased by one capsule, to a dose of 2 capsules barring side effects, at Week 2.
arm group label: Mirtazapine
arm group label: Placebo
other name: Remeron
intervention type: Drug
intervention name: Placebo
description: Gelatin capsules Placebo capsules, identical to mirtazapine capsules, 1 capsule every a.m. Medication will be increased by one capsule to 2 capsules at Week 2, barring any side effects.
arm group label: Mirtazapine
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Jack R Cornelius, M.D., M.P.H.
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: United States
citation: Cornelius JR, Douaihy AB, Clark DB, Chung T, Wood DS, Daley D. Mirtazapine in Comorbid Major Depression and Alcohol Dependence: An Open-Label Trial. J Dual Diagn. 2012 Sep 1;8(3):200-204. doi: 10.1080/15504263.2012.696527. Epub 2012 Aug 8.
PMID: 23230395
citation: Cornelius JR, Chung T, Douaihy AB, Kirisci L, Glance J, Kmiec J, FitzGerald D, Wesesky MA, Salloum I. Mirtazapine in comorbid major depression and an alcohol use disorder: A double-blind placebo-controlled pilot trial. Psychiatry Res. 2016 Aug 30;242:326-330. doi: 10.1016/j.psychres.2016.06.005. Epub 2016 Jun 15.
PMID: 27327217
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Jack Cornelius
investigator title: MD, PhD
mesh term: Alcoholism
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
mesh term: Alcohol Drinking
mesh term: Mirtazapine
sharing ipd: No
ipd description: No individual subject data will be shared.
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 