<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/NCT01662297</url>
  </required_header>
  <id_info>
    <org_study_id>Quetiapine-Trazodone Insomnia</org_study_id>
    <secondary_id>VA MIRB #01579</secondary_id>
    <nct_id>NCT01662297</nct_id>
  </id_info>
  <brief_title>Comparison of Quetiapine and Trazodone Treatment for Insomnia in Dually Diagnosed Veterans</brief_title>
  <official_title>Comparison of Quetiapine and Trazodone Treatment for Insomnia in Dually Diagnosed Veterans: an Open (e.g. Unblinded) Randomized Stay-Switch Pilot Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Connecticut Healthcare System</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VA Connecticut Healthcare System</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot comparative effectiveness study designed to determine whether trazodone is as&#xD;
      effective as quetiapine for treatment of insomnia in veterans with a history of addiction and&#xD;
      mental health issues. The study will have two concurrent phases (parts); first an&#xD;
      acceptability determination phase, to determine whether and why (or why not) veterans already&#xD;
      taking quetiapine are willing to try an alternative to quetiapine for sleep; and second, a&#xD;
      randomized trial phase which will test whether staying on quetiapine has any advantage over&#xD;
      switching to trazodone. The purpose of the first phase will be a) to document the proportions&#xD;
      of patients and physicians who are willing to agree to such a switch, b) to characterize&#xD;
      sociodemographic and clinical characteristics of potentially eligible subjects associated&#xD;
      with a willingness to switch from quetiapine to trazodone and c) to record the reasons given&#xD;
      why patients and their prescribers are (or are not) willing to accept a switch from&#xD;
      quetiapine to trazodone. It will also function to provide some educational background to&#xD;
      patients and a reminder to providers about the potential severe side-effects of quetiapine,&#xD;
      and will thus facilitate clinical informed consent for the clinical trial phase of the study.&#xD;
      Completion of the first part of the study will also serve as the screening component for part&#xD;
      II. Part II includes, first, obtaining written informed consent from eligible subjects, and&#xD;
      then randomly assigning them to continue quetiapine or to be switched to trazodone in&#xD;
      open-label &quot;real world&quot; fashion for the duration of 4 weeks, followed by another four weeks&#xD;
      of open, non-randomized follow- up. The purpose of the second part of the study is to&#xD;
      determine if trazodone is an adequate substitute for quetiapine, primarily in terms of&#xD;
      treating insomnia. The investigators hypothesize that trazodone will not be inferior to&#xD;
      quetiapine in maintaining good quality of sleep measured by sleep scales (i.e., scores will&#xD;
      not significantly worsen once switched). This study is open to Veterans in the VA system&#xD;
      only. Eligible subjects must have a history of &quot;dual diagnosis&quot; (i.e., a history of addiction&#xD;
      and mental illness).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Part I of the study involves identification through VA records of subjects eligible for the&#xD;
      study based on their prescription of quetiapine. Potentially eligible subjects will be&#xD;
      contacted by the research team. Subjects will answer a brief questionnaire about their&#xD;
      experience with the medication quetiapine as used for insomnia. If subjects are interested in&#xD;
      participated in part II, the clinical trial portion of the study, they will be further&#xD;
      screened for eligibility.&#xD;
&#xD;
      Part II consists of a 4 week clinical trial in which subjects are randomized to stay on&#xD;
      quetiapine or switch to trazodone, all of which will be open-label. Subjects will be&#xD;
      evaluated for symptoms of sleep quality and excessive daytime sleepiness. subjects will also&#xD;
      be assessed for changes in mood, and alcohol/drug use. After the initial 4 week treatment&#xD;
      period, subjects on trazodone can choose to switch back to quetiapine or continue on&#xD;
      trazodone. Subjects will also be evaluated after an additional 4 weeks (8weeks from start of&#xD;
      the study) on outcome measures.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    it became clear that recruitment was infeasible&#xD;
  </why_stopped>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">October 2015</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Average Pittsburgh Sleep Quality Inventory (PSQI)Score</measure>
    <time_frame>From baseline (week 0) to end of 4 week and end of week 8</time_frame>
    <description>Data analyzed for change from score at baseline, to week 4, to week 8. The range of scores is 0-21 on this scale, with higher scores indicating worse sleep quality. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL PSQI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The first four weeks of treatment is the active acute experiment phase, and this will be the main comparison time period for the endpoint, but the investigators will also analyze change in PSQI until the follow-up point at the end of week 8.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Insomnia Severity Index (ISI) Scores</measure>
    <time_frame>from baseline (week 0) to the end of week 4 and at week 8</time_frame>
    <description>THE RANGE OF SCORES IS FROM 0-28, WITH 28 REPRESENTING SEVERE INSOMNIA SYMPTOMS. Measurements made and reported at baseline, week 2, week 4. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. . This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL ISI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Epworth Sleepiness Scale (ESS) Over Time</measure>
    <time_frame>From baseline (week 0) to end of week 8</time_frame>
    <description>Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. The change from week 4 to week 8 (post-intervention) will also be measured and analyzed, reported. This is a comparison between groups (trazodone versus quetiapine)of the change on ESS scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).The minimum score on ESS is 0-24 units, with higher score representing greater sleepiness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in RAND Short Form 36 Item Health Survey (RAND-SF36) General Health Subscale Over Time</measure>
    <time_frame>from week 0 (baseline) to end of week 8</time_frame>
    <description>Scores range from 0-100 representing percentage, with a higher score representing better functioning. Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. The change from week 4 to week 8 (post-intervention) will also be measured and analyzed, reported. This is a comparison between groups (trazodone versus quetiapine)of the change on RAND-SF36 scores over time. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Brief Symptom Inventory (BSI) Over Time</measure>
    <time_frame>from week 0 (baseline) to end of week 8</time_frame>
    <description>The Brief Symptom Inventory scale measures a broad range of psychiatric symptoms (psychological distress) and is meant to provide an overall measure of mental health symptomatology. The BSI has 53 items that use a 5-item Likert scale response. In general, higher scores correspond to greater symptomatology and distress. Usually, the range of scores goes from 0 - 4, since it is averaged over the number of responses, however, we report the raw total score which is the sum of all responses, thus the range is 0-212. Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups of the change on BSI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Alcohol Urge Questionnaire (AUQ)Scores Over Time</measure>
    <time_frame>from week 0 (baseline) to end of week 8</time_frame>
    <description>The lowest possible score for the AUQ is 8 (representing less urge to drink) and the highest score would be a 56 (more urge to drink). Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups (trazodone versus quetiapine)of the change on AUQ scores over time. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Heavy Drinking Days</measure>
    <time_frame>from week 0 (baseline) to end of week 8</time_frame>
    <description>This is a comparison between groups of the mean percent heavy drinking days during the first 4 weeks, and then through to the follow up point (end of week 8). The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Negative Urine Drug Screens</measure>
    <time_frame>from week 0 (baseline) to end of week 8</time_frame>
    <description>This is a comparison between groups of the mean percent of negative urine drug screens. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8). THIS IS A CUMULATIVE PERCENTAGE. MAXIMUM SCORE IS 100%, MINIMUM 0%.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Medical Outcomes Study Sleep Scale- Sleep Index (Short)</measure>
    <time_frame>from baseline (week 0) to the end of week 8 sample</time_frame>
    <description>THE RANGE OF SCORES IS FROM 0-100, WITH 100 REPRESENTING SEVERE INSOMNIA SYMPTOMS. Measurements made and reported at baseline, week 2, week 4. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. . This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL MOS-SS scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Insomnia</condition>
  <condition>Mental Health Disorder</condition>
  <condition>Substance Use Disorder</condition>
  <arm_group>
    <arm_group_label>Quetiapine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Veterans remaining on quetiapine for insomnia.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Trazodone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Veterans switching from quetiapine to trazodone for the treatment of insomnia.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Quetiapine</intervention_name>
    <description>Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.</description>
    <arm_group_label>Quetiapine</arm_group_label>
    <other_name>Seroquel</other_name>
    <other_name>Quetiapine Fumarate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trazodone</intervention_name>
    <description>Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.</description>
    <arm_group_label>Trazodone</arm_group_label>
    <other_name>Desyrel</other_name>
    <other_name>Oleptro</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion/Exclusion Criteria (PHASE 1):&#xD;
&#xD;
          -  Identified by their VA prescribing provider as taking quetiapine primarily as a&#xD;
             sedative/hypnotic agent for some form of insomnia for at least 1 month&#xD;
&#xD;
          -  Identified by their VA prescribing provider as having dual diagnosis; a lifetime&#xD;
             history of substance use disorder and a mental disorder&#xD;
&#xD;
          -  Willing to meet with a research assistant to answer several questions regarding their&#xD;
             use of and experience with quetiapine.&#xD;
&#xD;
          -  Appear not to be regularly on any medication which would be an exclusion for Part II&#xD;
             (see Part II exclusion criteria).&#xD;
&#xD;
        Inclusion Criteria (PHASE 2):&#xD;
&#xD;
          -  Willing to provide written informed consent.&#xD;
&#xD;
          -  Provider reports that primary use of quetiapine is for insomnia for at least one month&#xD;
             and not primary or augmentation treatment of mood, anxiety disorder, psychosis, or&#xD;
             mood stabilization.&#xD;
&#xD;
          -  Have a self-identified and provider confirmed lifetime history of mental health and&#xD;
             substance use disorder (dual diagnosis).&#xD;
&#xD;
          -  Currently taking Quetiapine up to 300mg daily for the primary purpose of treating&#xD;
             insomnia, and have been taking it for at least 1 month (30 days).&#xD;
&#xD;
          -  Use of an acceptable method of birth control by female patients who have a possibility&#xD;
             of becoming pregnant.&#xD;
&#xD;
          -  The provider should review the patients from the identified charts, and fill out&#xD;
             information about the patient and why they are on the drug, and provider should&#xD;
             consent to us approaching the client and potentially switching them; the investigators&#xD;
             will not approach and begin enrollment for part II on subjects if their provider feels&#xD;
             it is not appropriate for them for any reason.&#xD;
&#xD;
        Exclusion Criteria (PHASE 2):&#xD;
&#xD;
          -  Physiologic substance dependence requiring detoxification in the past 30 days&#xD;
             (substance abuse is not an exclusion).&#xD;
&#xD;
          -  Concomitant administration of: other sedative hypnotics, benzodiazepines, prazosin,&#xD;
             other atypical antipsychotics, stimulants, ketoconazole and other inhibitors of&#xD;
             cytochrome P450 3A (e.g., itraconazole, fluconazole, erythromycin, and protease&#xD;
             inhibitors), phenytoin or other strong inducers of cytochrome P450 enzymes.&#xD;
&#xD;
          -  Intolerance or hypersensitivity to trazodone.&#xD;
&#xD;
          -  Pregnant or lactating women or women planning to become pregnant.&#xD;
&#xD;
          -  Hepatic or renal problems AST or ALT (&gt;3 times upper limit of normal);&#xD;
&#xD;
          -  Elevated bilirubin (&gt;1.2), BUN (&gt;24), creatinine (&gt;1.7).&#xD;
&#xD;
          -  Unstable, serious medical condition or one requiring acute medical treatment, or&#xD;
             anticipation of hospitalization for extended care.&#xD;
&#xD;
          -  Dementia, epilepsy, insulin-dependent diabetes, anticoagulation with coumadin.&#xD;
&#xD;
          -  Legal entanglements or pending legal charges with potential of incarceration.&#xD;
&#xD;
          -  Recent (i.e., past 3 months) assault or suicide gesture currently needing acute&#xD;
             intervention.&#xD;
&#xD;
          -  Concurrent participation in another clinical trial with an investigational drug during&#xD;
             the last 30 days.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Albert J Arias, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University/Veterans Affairs CT</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Elizabeth Ralevski, Ph.D.</last_name>
    <role>Study Director</role>
    <affiliation>Yale University/Veterans Affairs CT</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>VA Connecticut Healthcare System</name>
      <address>
        <city>West Haven</city>
        <state>Connecticut</state>
        <zip>06516</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>July 16, 2012</study_first_submitted>
  <study_first_submitted_qc>August 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 10, 2012</study_first_posted>
  <results_first_submitted>October 19, 2015</results_first_submitted>
  <results_first_submitted_qc>October 14, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">October 16, 2018</results_first_posted>
  <last_update_submitted>October 14, 2018</last_update_submitted>
  <last_update_submitted_qc>October 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 16, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Quetiapine</keyword>
  <keyword>Trazodone</keyword>
  <keyword>Insomnia</keyword>
  <keyword>Dual Diagnosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sleep Initiation and Maintenance Disorders</mesh_term>
    <mesh_term>Substance-Related Disorders</mesh_term>
    <mesh_term>Mental Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Quetiapine Fumarate</mesh_term>
    <mesh_term>Trazodone</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Quetiapine</title>
          <description>Veterans remaining on quetiapine for insomnia.&#xD;
Quetiapine: Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.</description>
        </group>
        <group group_id="P2">
          <title>Trazodone</title>
          <description>Veterans switching from quetiapine to trazodone for the treatment of insomnia.&#xD;
Trazodone: Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Quetiapine</title>
          <description>Veterans remaining on quetiapine for insomnia.&#xD;
Quetiapine: Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.</description>
        </group>
        <group group_id="B2">
          <title>Trazodone</title>
          <description>Veterans switching from quetiapine to trazodone for the treatment of insomnia.&#xD;
Trazodone: Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.</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="0"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="1"/>
          </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="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B2" value="60" lower_limit="60" upper_limit="60"/>
                    <measurement group_id="B3" value="60" lower_limit="60" upper_limit="60"/>
                  </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="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </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="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Average Pittsburgh Sleep Quality Inventory (PSQI)Score</title>
        <description>Data analyzed for change from score at baseline, to week 4, to week 8. The range of scores is 0-21 on this scale, with higher scores indicating worse sleep quality. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL PSQI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The first four weeks of treatment is the active acute experiment phase, and this will be the main comparison time period for the endpoint, but the investigators will also analyze change in PSQI until the follow-up point at the end of week 8.</description>
        <time_frame>From baseline (week 0) to end of 4 week and end of week 8</time_frame>
        <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Quetiapine</title>
            <description>Veterans remaining on quetiapine for insomnia.&#xD;
Quetiapine: Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.</description>
          </group>
          <group group_id="O2">
            <title>Trazodone</title>
            <description>Veterans switching from quetiapine to trazodone for the treatment of insomnia.&#xD;
Trazodone: Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Average Pittsburgh Sleep Quality Inventory (PSQI)Score</title>
          <description>Data analyzed for change from score at baseline, to week 4, to week 8. The range of scores is 0-21 on this scale, with higher scores indicating worse sleep quality. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL PSQI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The first four weeks of treatment is the active acute experiment phase, and this will be the main comparison time period for the endpoint, but the investigators will also analyze change in PSQI until the follow-up point at the end of week 8.</description>
          <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
          <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="0"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>change at week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="-11" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>change at week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="-11" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Insomnia Severity Index (ISI) Scores</title>
        <description>THE RANGE OF SCORES IS FROM 0-28, WITH 28 REPRESENTING SEVERE INSOMNIA SYMPTOMS. Measurements made and reported at baseline, week 2, week 4. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. . This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL ISI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).</description>
        <time_frame>from baseline (week 0) to the end of week 4 and at week 8</time_frame>
        <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Quetiapine</title>
            <description>Veterans remaining on quetiapine for insomnia.&#xD;
Quetiapine: Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.</description>
          </group>
          <group group_id="O2">
            <title>Trazodone</title>
            <description>Veterans switching from quetiapine to trazodone for the treatment of insomnia.&#xD;
Trazodone: Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Insomnia Severity Index (ISI) Scores</title>
          <description>THE RANGE OF SCORES IS FROM 0-28, WITH 28 REPRESENTING SEVERE INSOMNIA SYMPTOMS. Measurements made and reported at baseline, week 2, week 4. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. . This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL ISI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).</description>
          <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
          <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="0"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>change at week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="-14" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>change at week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="-16" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Epworth Sleepiness Scale (ESS) Over Time</title>
        <description>Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. The change from week 4 to week 8 (post-intervention) will also be measured and analyzed, reported. This is a comparison between groups (trazodone versus quetiapine)of the change on ESS scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).The minimum score on ESS is 0-24 units, with higher score representing greater sleepiness.</description>
        <time_frame>From baseline (week 0) to end of week 8</time_frame>
        <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Quetiapine</title>
            <description>Veterans remaining on quetiapine for insomnia.&#xD;
Quetiapine: Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.</description>
          </group>
          <group group_id="O2">
            <title>Trazodone</title>
            <description>Veterans switching from quetiapine to trazodone for the treatment of insomnia.&#xD;
Trazodone: Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Epworth Sleepiness Scale (ESS) Over Time</title>
          <description>Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. The change from week 4 to week 8 (post-intervention) will also be measured and analyzed, reported. This is a comparison between groups (trazodone versus quetiapine)of the change on ESS scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).The minimum score on ESS is 0-24 units, with higher score representing greater sleepiness.</description>
          <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
          <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="0"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>change at week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="-3" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>change at week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="-4" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in RAND Short Form 36 Item Health Survey (RAND-SF36) General Health Subscale Over Time</title>
        <description>Scores range from 0-100 representing percentage, with a higher score representing better functioning. Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. The change from week 4 to week 8 (post-intervention) will also be measured and analyzed, reported. This is a comparison between groups (trazodone versus quetiapine)of the change on RAND-SF36 scores over time. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).</description>
        <time_frame>from week 0 (baseline) to end of week 8</time_frame>
        <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Quetiapine</title>
            <description>Veterans remaining on quetiapine for insomnia.&#xD;
Quetiapine: Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.</description>
          </group>
          <group group_id="O2">
            <title>Trazodone</title>
            <description>Veterans switching from quetiapine to trazodone for the treatment of insomnia.&#xD;
Trazodone: Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in RAND Short Form 36 Item Health Survey (RAND-SF36) General Health Subscale Over Time</title>
          <description>Scores range from 0-100 representing percentage, with a higher score representing better functioning. Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. The change from week 4 to week 8 (post-intervention) will also be measured and analyzed, reported. This is a comparison between groups (trazodone versus quetiapine)of the change on RAND-SF36 scores over time. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).</description>
          <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
          <units>percentage of total points possible</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>change at week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="15" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>change at week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="0" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Brief Symptom Inventory (BSI) Over Time</title>
        <description>The Brief Symptom Inventory scale measures a broad range of psychiatric symptoms (psychological distress) and is meant to provide an overall measure of mental health symptomatology. The BSI has 53 items that use a 5-item Likert scale response. In general, higher scores correspond to greater symptomatology and distress. Usually, the range of scores goes from 0 - 4, since it is averaged over the number of responses, however, we report the raw total score which is the sum of all responses, thus the range is 0-212. Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups of the change on BSI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments.</description>
        <time_frame>from week 0 (baseline) to end of week 8</time_frame>
        <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Quetiapine</title>
            <description>Veterans remaining on quetiapine for insomnia.&#xD;
Quetiapine: Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.</description>
          </group>
          <group group_id="O2">
            <title>Trazodone</title>
            <description>Veterans switching from quetiapine to trazodone for the treatment of insomnia.&#xD;
Trazodone: Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Brief Symptom Inventory (BSI) Over Time</title>
          <description>The Brief Symptom Inventory scale measures a broad range of psychiatric symptoms (psychological distress) and is meant to provide an overall measure of mental health symptomatology. The BSI has 53 items that use a 5-item Likert scale response. In general, higher scores correspond to greater symptomatology and distress. Usually, the range of scores goes from 0 - 4, since it is averaged over the number of responses, however, we report the raw total score which is the sum of all responses, thus the range is 0-212. Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups of the change on BSI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments.</description>
          <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
          <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="0"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>change at week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="-48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>change at week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="-48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Alcohol Urge Questionnaire (AUQ)Scores Over Time</title>
        <description>The lowest possible score for the AUQ is 8 (representing less urge to drink) and the highest score would be a 56 (more urge to drink). Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups (trazodone versus quetiapine)of the change on AUQ scores over time. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).</description>
        <time_frame>from week 0 (baseline) to end of week 8</time_frame>
        <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Quetiapine</title>
            <description>Veterans remaining on quetiapine for insomnia.&#xD;
Quetiapine: Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.</description>
          </group>
          <group group_id="O2">
            <title>Trazodone</title>
            <description>Veterans switching from quetiapine to trazodone for the treatment of insomnia.&#xD;
Trazodone: Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Alcohol Urge Questionnaire (AUQ)Scores Over Time</title>
          <description>The lowest possible score for the AUQ is 8 (representing less urge to drink) and the highest score would be a 56 (more urge to drink). Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups (trazodone versus quetiapine)of the change on AUQ scores over time. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).</description>
          <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
          <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="0"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>change after week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="-1" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>change after week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="-12" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Heavy Drinking Days</title>
        <description>This is a comparison between groups of the mean percent heavy drinking days during the first 4 weeks, and then through to the follow up point (end of week 8). The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).</description>
        <time_frame>from week 0 (baseline) to end of week 8</time_frame>
        <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Quetiapine</title>
            <description>Veterans remaining on quetiapine for insomnia.&#xD;
Quetiapine: Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.</description>
          </group>
          <group group_id="O2">
            <title>Trazodone</title>
            <description>Veterans switching from quetiapine to trazodone for the treatment of insomnia.&#xD;
Trazodone: Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Heavy Drinking Days</title>
          <description>This is a comparison between groups of the mean percent heavy drinking days during the first 4 weeks, and then through to the follow up point (end of week 8). The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).</description>
          <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
          <units>percentage of heavy drinking days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>percentage at week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="0" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>percentage at week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="0" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Negative Urine Drug Screens</title>
        <description>This is a comparison between groups of the mean percent of negative urine drug screens. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8). THIS IS A CUMULATIVE PERCENTAGE. MAXIMUM SCORE IS 100%, MINIMUM 0%.</description>
        <time_frame>from week 0 (baseline) to end of week 8</time_frame>
        <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Quetiapine</title>
            <description>Veterans remaining on quetiapine for insomnia.&#xD;
Quetiapine: Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.</description>
          </group>
          <group group_id="O2">
            <title>Trazodone</title>
            <description>Veterans switching from quetiapine to trazodone for the treatment of insomnia.&#xD;
Trazodone: Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Negative Urine Drug Screens</title>
          <description>This is a comparison between groups of the mean percent of negative urine drug screens. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8). THIS IS A CUMULATIVE PERCENTAGE. MAXIMUM SCORE IS 100%, MINIMUM 0%.</description>
          <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
          <units>percentage of tests</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>cumulative percentage at week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="0" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cumulative percentage at week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="0" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Medical Outcomes Study Sleep Scale- Sleep Index (Short)</title>
        <description>THE RANGE OF SCORES IS FROM 0-100, WITH 100 REPRESENTING SEVERE INSOMNIA SYMPTOMS. Measurements made and reported at baseline, week 2, week 4. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. . This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL MOS-SS scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).</description>
        <time_frame>from baseline (week 0) to the end of week 8 sample</time_frame>
        <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Quetiapine</title>
            <description>Veterans remaining on quetiapine for insomnia.&#xD;
Quetiapine: Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.</description>
          </group>
          <group group_id="O2">
            <title>Trazodone</title>
            <description>Veterans switching from quetiapine to trazodone for the treatment of insomnia.&#xD;
Trazodone: Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Medical Outcomes Study Sleep Scale- Sleep Index (Short)</title>
          <description>THE RANGE OF SCORES IS FROM 0-100, WITH 100 REPRESENTING SEVERE INSOMNIA SYMPTOMS. Measurements made and reported at baseline, week 2, week 4. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. . This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL MOS-SS scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).</description>
          <population>We had difficulty recruiting and retaining subjects for this study. 3 subjects were randomized and only 1 provided data beyond baseline.</population>
          <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="0"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>change at 4 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="-13.33" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>change at 8 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="-26.66" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>8 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Quetiapine</title>
          <description>Veterans remaining on quetiapine for insomnia.&#xD;
Quetiapine: Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.</description>
        </group>
        <group group_id="E2">
          <title>Trazodone</title>
          <description>Veterans switching from quetiapine to trazodone for the treatment of insomnia.&#xD;
Trazodone: Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="0"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <description>This patient died after completing the study and the 8 week follow up session. Subject died on 4/30/2013, several weeks after completing the follow up period for the study (4/8/13). The death was clearly unrelated to study participation.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea/Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </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. Albert Arias</name_or_title>
      <organization>Yale University/West Haven VAMC</organization>
      <phone>2039325711 ext 8155</phone>
      <email>albert.arias@va.gov</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/NCT01662297
org study id: Quetiapine-Trazodone Insomnia
secondary id: VA MIRB #01579
nct id: NCT01662297
lead sponsor: 
has dmc: Yes
This is a pilot comparative effectiveness study designed to determine whether trazodone is as
      effective as quetiapine for treatment of insomnia in veterans with a history of addiction and
      mental health issues. The study will have two concurrent phases (parts); first an
      acceptability determination phase, to determine whether and why (or why not) veterans already
      taking quetiapine are willing to try an alternative to quetiapine for sleep; and second, a
      randomized trial phase which will test whether staying on quetiapine has any advantage over
      switching to trazodone. The purpose of the first phase will be a) to document the proportions
      of patients and physicians who are willing to agree to such a switch, b) to characterize
      sociodemographic and clinical characteristics of potentially eligible subjects associated
      with a willingness to switch from quetiapine to trazodone and c) to record the reasons given
      why patients and their prescribers are (or are not) willing to accept a switch from
      quetiapine to trazodone. It will also function to provide some educational background to
      patients and a reminder to providers about the potential severe side-effects of quetiapine,
      and will thus facilitate clinical informed consent for the clinical trial phase of the study.
      Completion of the first part of the study will also serve as the screening component for part
      II. Part II includes, first, obtaining written informed consent from eligible subjects, and
      then randomly assigning them to continue quetiapine or to be switched to trazodone in
      open-label "real world" fashion for the duration of 4 weeks, followed by another four weeks
      of open, non-randomized follow- up. The purpose of the second part of the study is to
      determine if trazodone is an adequate substitute for quetiapine, primarily in terms of
      treating insomnia. The investigators hypothesize that trazodone will not be inferior to
      quetiapine in maintaining good quality of sleep measured by sleep scales (i.e., scores will
      not significantly worsen once switched). This study is open to Veterans in the VA system
      only. Eligible subjects must have a history of "dual diagnosis" (i.e., a history of addiction
      and mental illness).
Part I of the study involves identification through VA records of subjects eligible for the
      study based on their prescription of quetiapine. Potentially eligible subjects will be
      contacted by the research team. Subjects will answer a brief questionnaire about their
      experience with the medication quetiapine as used for insomnia. If subjects are interested in
      participated in part II, the clinical trial portion of the study, they will be further
      screened for eligibility.

      Part II consists of a 4 week clinical trial in which subjects are randomized to stay on
      quetiapine or switch to trazodone, all of which will be open-label. Subjects will be
      evaluated for symptoms of sleep quality and excessive daytime sleepiness. subjects will also
      be assessed for changes in mood, and alcohol/drug use. After the initial 4 week treatment
      period, subjects on trazodone can choose to switch back to quetiapine or continue on
      trazodone. Subjects will also be evaluated after an additional 4 weeks (8weeks from start of
      the study) on outcome measures.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Average Pittsburgh Sleep Quality Inventory (PSQI)Score
time frame: From baseline (week 0) to end of 4 week and end of week 8
description: Data analyzed for change from score at baseline, to week 4, to week 8. The range of scores is 0-21 on this scale, with higher scores indicating worse sleep quality. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL PSQI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The first four weeks of treatment is the active acute experiment phase, and this will be the main comparison time period for the endpoint, but the investigators will also analyze change in PSQI until the follow-up point at the end of week 8.
measure: Change in Insomnia Severity Index (ISI) Scores
time frame: from baseline (week 0) to the end of week 4 and at week 8
description: THE RANGE OF SCORES IS FROM 0-28, WITH 28 REPRESENTING SEVERE INSOMNIA SYMPTOMS. Measurements made and reported at baseline, week 2, week 4. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. . This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL ISI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).
measure: Change in Epworth Sleepiness Scale (ESS) Over Time
time frame: From baseline (week 0) to end of week 8
description: Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. The change from week 4 to week 8 (post-intervention) will also be measured and analyzed, reported. This is a comparison between groups (trazodone versus quetiapine)of the change on ESS scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).The minimum score on ESS is 0-24 units, with higher score representing greater sleepiness.
measure: Change in RAND Short Form 36 Item Health Survey (RAND-SF36) General Health Subscale Over Time
time frame: from week 0 (baseline) to end of week 8
description: Scores range from 0-100 representing percentage, with a higher score representing better functioning. Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. The change from week 4 to week 8 (post-intervention) will also be measured and analyzed, reported. This is a comparison between groups (trazodone versus quetiapine)of the change on RAND-SF36 scores over time. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).
measure: Change in Brief Symptom Inventory (BSI) Over Time
time frame: from week 0 (baseline) to end of week 8
description: The Brief Symptom Inventory scale measures a broad range of psychiatric symptoms (psychological distress) and is meant to provide an overall measure of mental health symptomatology. The BSI has 53 items that use a 5-item Likert scale response. In general, higher scores correspond to greater symptomatology and distress. Usually, the range of scores goes from 0 - 4, since it is averaged over the number of responses, however, we report the raw total score which is the sum of all responses, thus the range is 0-212. Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups of the change on BSI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments.
measure: Change in Alcohol Urge Questionnaire (AUQ)Scores Over Time
time frame: from week 0 (baseline) to end of week 8
description: The lowest possible score for the AUQ is 8 (representing less urge to drink) and the highest score would be a 56 (more urge to drink). Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups (trazodone versus quetiapine)of the change on AUQ scores over time. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).
measure: Percentage of Heavy Drinking Days
time frame: from week 0 (baseline) to end of week 8
description: This is a comparison between groups of the mean percent heavy drinking days during the first 4 weeks, and then through to the follow up point (end of week 8). The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).
measure: Percentage of Negative Urine Drug Screens
time frame: from week 0 (baseline) to end of week 8
description: This is a comparison between groups of the mean percent of negative urine drug screens. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8). THIS IS A CUMULATIVE PERCENTAGE. MAXIMUM SCORE IS 100%, MINIMUM 0%.
measure: Medical Outcomes Study Sleep Scale- Sleep Index (Short)
time frame: from baseline (week 0) to the end of week 8 sample
description: THE RANGE OF SCORES IS FROM 0-100, WITH 100 REPRESENTING SEVERE INSOMNIA SYMPTOMS. Measurements made and reported at baseline, week 2, week 4. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. . This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL MOS-SS scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).
arm group label: Quetiapine
arm group type: Active Comparator
description: Veterans remaining on quetiapine for insomnia.
arm group label: Trazodone
arm group type: Active Comparator
description: Veterans switching from quetiapine to trazodone for the treatment of insomnia.
intervention type: Drug
intervention name: Quetiapine
description: Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.
arm group label: Quetiapine
other name: Seroquel
other name: Quetiapine Fumarate
intervention type: Drug
intervention name: Trazodone
description: Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.
arm group label: Trazodone
other name: Desyrel
other name: Oleptro
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Albert J Arias, MD, MS
role: Principal Investigator
affiliation: Yale University/Veterans Affairs CT
last name: Elizabeth Ralevski, Ph.D.
role: Study Director
affiliation: Yale University/Veterans Affairs CT
facility: 
country: United States
responsible party type: Sponsor
mesh term: Sleep Initiation and Maintenance Disorders
mesh term: Substance-Related Disorders
mesh term: Mental Disorders
mesh term: Quetiapine Fumarate
mesh term: Trazodone
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 