<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/NCT01689909</url>
  </required_header>
  <id_info>
    <org_study_id>1R01MH095776-01A1</org_study_id>
    <secondary_id>1R01MH095776</secondary_id>
    <nct_id>NCT01689909</nct_id>
  </id_info>
  <brief_title>Reducing Suicidal Ideation Through Insomnia Treatment</brief_title>
  <acronym>REST-IT</acronym>
  <official_title>Reducing Suicidal Ideation Through Insomnia Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Augusta University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Augusta University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Epidemiologic reports have linked insomnia to suicidal ideation and suicide death. However,&#xD;
      no studies have determined whether treating insomnia decreases the risk of suicidality. We&#xD;
      have new data indicating that (1) the link between insomnia and suicidal ideation holds true&#xD;
      in clinical trials of depressed insomniacs, (2) dysfunctional cognitions about sleep are&#xD;
      related to suicidal ideas, and (3) treatment of insomnia with hypnotics leads to a reduction&#xD;
      of suicidal ideation. We now propose to test whether cautious use of hypnotics in suicidal,&#xD;
      depressed insomniacs may reduce suicide risk in a multi-site clinical trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Aim: We will assess the effect of treating insomnia with hypnotic medication on the&#xD;
      intensity of suicidal ideation in depressed outpatients with insomnia and suicidal ideation.&#xD;
&#xD;
      -Hypothesis 1. Treatment of depressed, insomniac and suicidal outpatients with open-label&#xD;
      fluoxetine (FLX) and blinded zolpidem controlled release (ZOL) will reduce suicidal ideation&#xD;
      more than treatment with FLX and blinded placebo.&#xD;
&#xD;
      Secondary Aim: We will examine whether reduced suicidal ideation in depressed insomniacs is&#xD;
      mediated through reduced dysfunctional beliefs about sleep, reduced hopelessness, or fewer&#xD;
      nightmares.&#xD;
&#xD;
        -  Hypothesis 2a. Reduction in suicidal ideation will be mediated through reductions in&#xD;
           dysfunctional beliefs about sleep.&#xD;
&#xD;
        -  Hypothesis 2b. Reduction in suicidal ideation will be mediated through reductions in&#xD;
           hopelessness.&#xD;
&#xD;
        -  Hypothesis 2c. Reduction in suicidal ideation is mediated through fewer nightmares.&#xD;
&#xD;
      Tertiary Aim: We will confirm findings from our prior pilot studies that treatment of&#xD;
      insomnia in depressed insomniacs leads to improvements in health-related quality of life,&#xD;
      especially in women.&#xD;
&#xD;
      Exploratory Aim: We will archive actigraphy data to permit future examination to confirm our&#xD;
      preliminary data that actigraphic activity decreases as suicidal ideation resolves.&#xD;
&#xD;
      Overview of the Need for and Management of a Collaborative Application: The sample sizes&#xD;
      required to satisfy the Aims are relatively large, necessitating the pooled recruiting&#xD;
      resources of 3 sites. Georgia Regents University (GRU) will serve both as the&#xD;
      coordinating/data management site, as well as a recruiting site, with Duke and Wisconsin as&#xD;
      recruiting sites. Project management will be coordinated through an Executive Committee of&#xD;
      site principal investigators, under the supervision of a Data and Safety Monitoring Board.&#xD;
&#xD;
      Impact on the Field: This application has the potential to change providers' practice in the&#xD;
      approach to treating insomnia in depressed patients with mild-moderate suicidal ideation. It&#xD;
      may also reveal the mechanisms whereby insomnia increases the risk for suicidal ideation and&#xD;
      behavior, and begin to examine whether there is an actigraphic &quot;signature&quot; for reductions in&#xD;
      suicidal ideation. When these lessons are applied to the clinical world, they can be applied&#xD;
      with low cost.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 6, 2012</start_date>
  <completion_date type="Actual">January 1, 2018</completion_date>
  <primary_completion_date type="Actual">June 2017</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Scale for Suicide Ideation Index (SSI)</measure>
    <time_frame>Over 8 weeks of treatment</time_frame>
    <description>This is the total score for the Scale for Suicide Ideation. It has 19 items, each scored 0-2, for a maximum of 38 points. Higher scores indicate worse suicidal ideation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Columbia Suicide Severity Rating Scale (C-SSRS): the Suicidal Ideation Scale</measure>
    <time_frame>8 weeks of treatment</time_frame>
    <description>The suicide ideation scale of the C-SSRS is rated 0-5, with &quot;0&quot; meaning no suicidal ideation, &quot;1&quot; meaning a wish t be dead, &quot;2&quot; meaning non-specific active suicidal thoughts, &quot;3&quot; meaning active suicidal ideation with any methods but no plan or intent, &quot;4&quot; meaning active suicidal ideation with some intent but no specific plan, and &quot;5&quot; meaning active suicidal ideation with intent and a specific plan</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Dysfunctional Beliefs and Attitudes About Sleep</measure>
    <time_frame>8 weeks of treatment</time_frame>
    <description>The Dysfunctional Beliefs and Attitudes About Sleep scale has 16 items and is self administered. Each item is scored 0-10. The total score is an average of the scores of the 16 items. Hence the range of the total score is also 0-10, with higher scores indicating greater dysfunctional beliefs about sleep</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disturbing Dreams and Nightmares Severity Index (DDNSI)</measure>
    <time_frame>8 weeks of treatment</time_frame>
    <description>This self-rated scale has 5 items, with asymmetric weighting of each item. The range of the total score is 0-37, with higher scores indicating worse nightmares</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Beck Hopelessness Scale (BHS)</measure>
    <time_frame>8 weeks of treatment</time_frame>
    <description>The Beck Hopelessness Scale is self administered and has 20 'true/false' choices. Some items are reversed scored. The range of scores for the total is 0-20, with higher scores indicating greater hopelessness</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hamilton Rating Scale for Depression (HAM-D)</measure>
    <time_frame>8 weeks of treatment</time_frame>
    <description>This version of the Hamilton Rating Scale for Depression uses 24 items, with a possible total score ranging from 0-74, with higher scores indicating worse depression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insomnia Severity Index (ISI)</measure>
    <time_frame>8 weeks of treatment</time_frame>
    <description>The Insomnia Severity Index is self rated. It has 7 items, each scored 0-4. Therefore the range of scores is 0-28, with higher scores indicating worse insomnia</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Basis-32 - the Daily Living and Role Functioning (DLRF) Subscale</measure>
    <time_frame>8 weeks of treatment</time_frame>
    <description>This is one of the subscales of the Basis 32. It is self-administered. This subscale has 7 items, each scored 0-4. The totals score is an average of the scores of these 7 items. Higher scores indicate more difficulty with daily living and role functioning.</description>
  </other_outcome>
  <other_outcome>
    <measure>Actigraphy</measure>
    <time_frame>8 weeks of treatment</time_frame>
    <description>This device measures arm motion over time, reported as &quot;average actigraphic activity Level&quot;. The scale is reported as a continuous measure ranging from 0-200, and reported as the average score for each hour for all 24-hours of the day. Higher score represent greater c=activity at that point in time</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">103</enrollment>
  <condition>Insomnia</condition>
  <condition>Depression</condition>
  <condition>Suicidal Ideation</condition>
  <arm_group>
    <arm_group_label>Zolpidem-CR</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zolpidem-CR</intervention_name>
    <description>Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
    <arm_group_label>Zolpidem-CR</arm_group_label>
    <other_name>Ambien CR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Persons 18-65 years of age&#xD;
&#xD;
          -  Persons with confirmed DSM-IV diagnosis of MDE by SCID&#xD;
&#xD;
          -  Persons with Research Diagnostic Criteria diagnosis of insomnia&#xD;
&#xD;
          -  Persons free of all psychotropic medications for one week before baseline assessment,&#xD;
             except that prior FLX treatment will require 4 weeks of abstinence, and MAOIs will&#xD;
             require 2 weeks of abstinence.&#xD;
&#xD;
          -  Persons with Scale for Suicide Ideation (SSI) scores &gt;2&#xD;
&#xD;
          -  Persons with Hamilton Rating Scale for Depression (HRSD24) score &gt;20&#xD;
&#xD;
          -  Persons with Mini Mental State Exam (MMSE) score &gt;24&#xD;
&#xD;
          -  Persons with Insomnia Severity Index (ISI) score &gt; 7&#xD;
&#xD;
          -  Persons with habitual sleep latency &gt; or = 30 minutes or wake time in the middle of&#xD;
             the night of &gt; or = 30 minutes, and sleep efficiency &lt; 85%&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-English speaking, reading, writing persons&#xD;
&#xD;
          -  Persons who pose imminent danger to self or others&#xD;
&#xD;
          -  Persons with severe suicidal ideation (C-SSRS Suicidal Ideation Score &gt;3)&#xD;
&#xD;
          -  Persons with clinical diagnosis of dementia&#xD;
&#xD;
          -  Persons with active or past diagnosis of alcohol or substance abuse, bipolar disorder,&#xD;
             schizophrenia per the SCID&#xD;
&#xD;
          -  Persons who screen positive for moderate-severe sleep apnea (AHI &gt;10) or a prior sleep&#xD;
             laboratory-confirmed diagnosis of a primary sleep disorder, such as sleep apnea or&#xD;
             periodic limb movement disorder.&#xD;
&#xD;
          -  Persons with BMI &gt; 50&#xD;
&#xD;
          -  Persons with a self-reported history of napping &gt; 2 times per week (as these are&#xD;
             associated with sleep apnea and periodic limb movement disorder in depressed&#xD;
             insomniacs)&#xD;
&#xD;
          -  Persons who might be harmed by exposure to hypnotics, including pregnant women and&#xD;
             patients with respiratory conditions&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>William V McCall, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Augusta University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Georgia Regents University</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University School of Medicine</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest University School of Medicine</name>
      <address>
        <city>Wake Forest</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin- Madison</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53719</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>September 18, 2012</study_first_submitted>
  <study_first_submitted_qc>September 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <results_first_submitted>April 13, 2018</results_first_submitted>
  <results_first_submitted_qc>June 19, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">June 20, 2018</results_first_posted>
  <last_update_submitted>February 14, 2022</last_update_submitted>
  <last_update_submitted_qc>February 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Insomnia</keyword>
  <keyword>Depression</keyword>
  <keyword>Suicidal ideation</keyword>
  <keyword>Zolpidem CR</keyword>
  <keyword>Placebo</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>Depression</mesh_term>
    <mesh_term>Suicidal Ideation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Zolpidem</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 8, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/09/NCT01689909/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Zolpidem-CR</title>
          <description>Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="51"/>
                <participants group_id="P2" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="51"/>
                <participants group_id="P2" count="52"/>
              </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>Zolpidem-CR</title>
          <description>Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks</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="51"/>
            <count group_id="B2" value="52"/>
            <count group_id="B3" value="103"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="103"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="39.7" spread="14.5"/>
                    <measurement group_id="B2" value="41.2" spread="12.0"/>
                    <measurement group_id="B3" value="40.5" spread="13.2"/>
                  </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="32"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="64"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="47"/>
                    <measurement group_id="B2" value="51"/>
                    <measurement group_id="B3" value="98"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="68"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="103"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Scale for Suicide Ideation</title>
          <description>This is the total score for the Scale for Suicide Ideation. It has 19 items, each scored 0-2, for a maximum of 38 points. Higher scores indicate worse suicidal ideation</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12.2" spread="5.3"/>
                    <measurement group_id="B2" value="11.8" spread="5.3"/>
                    <measurement group_id="B3" value="12.0" spread="5.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Columbia Suicide Severity Rating Scale (C-SSRS) - suicide ideation scale</title>
          <description>The suicide ideation scale of the C-SSRS is rated 0-5, with &quot;0&quot; meaning no suicidal ideation, &quot;1&quot; meaning a wish to be dead, &quot;2&quot; meaning non-specific active suicidal thoughts, &quot;3&quot; meaning active suicidal ideation with any methods but no plan or intent, &quot;4&quot; meaning active suicidal ideation with some intent but no specific plan, and &quot;5&quot; meaning active suicidal ideation with intent and a specific plan.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.71" spread="10.3"/>
                    <measurement group_id="B2" value="1.58" spread="10.2"/>
                    <measurement group_id="B3" value="1.64" spread="1.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hamilton Rating Scale for Depression -24</title>
          <description>This version of the Hamilton Rating Scale for Depression uses 24 items, with a possible total score ranging from 0-74, with higher scores indicating worse depression</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28.7" spread="4.7"/>
                    <measurement group_id="B2" value="29.6" spread="7.0"/>
                    <measurement group_id="B3" value="29.1" spread="5.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Disturbing Dreams Nightmare Severity Index</title>
          <description>This self-rated scale has 5 items, with asymmetric weighting of each item. The range of the total score is 0-37, with higher scores indicating worse nightmares</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10.5" spread="8.8"/>
                    <measurement group_id="B2" value="10.2" spread="7.7"/>
                    <measurement group_id="B3" value="10.3" spread="8.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Insomnia Severity Index</title>
          <description>The Insomnia Severity Index is self rated. It has 7 items, each scored 0-4. Therefore the range of scores is 0-28, with higher scores indicating worse insomnia</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20.6" spread="3.9"/>
                    <measurement group_id="B2" value="21.1" spread="4.3"/>
                    <measurement group_id="B3" value="20.8" spread="4.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Scale for Suicide Ideation Index (SSI)</title>
        <description>This is the total score for the Scale for Suicide Ideation. It has 19 items, each scored 0-2, for a maximum of 38 points. Higher scores indicate worse suicidal ideation</description>
        <time_frame>Over 8 weeks of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Zolpidem-CR</title>
            <description>Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Scale for Suicide Ideation Index (SSI)</title>
          <description>This is the total score for the Scale for Suicide Ideation. It has 19 items, each scored 0-2, for a maximum of 38 points. Higher scores indicate worse suicidal ideation</description>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.66" spread="0.58"/>
                    <measurement group_id="O2" value="5.25" spread="0.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Columbia Suicide Severity Rating Scale (C-SSRS): the Suicidal Ideation Scale</title>
        <description>The suicide ideation scale of the C-SSRS is rated 0-5, with &quot;0&quot; meaning no suicidal ideation, &quot;1&quot; meaning a wish t be dead, &quot;2&quot; meaning non-specific active suicidal thoughts, &quot;3&quot; meaning active suicidal ideation with any methods but no plan or intent, &quot;4&quot; meaning active suicidal ideation with some intent but no specific plan, and &quot;5&quot; meaning active suicidal ideation with intent and a specific plan</description>
        <time_frame>8 weeks of treatment</time_frame>
        <population>all evaluable randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>Zolpidem-CR</title>
            <description>Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Columbia Suicide Severity Rating Scale (C-SSRS): the Suicidal Ideation Scale</title>
          <description>The suicide ideation scale of the C-SSRS is rated 0-5, with &quot;0&quot; meaning no suicidal ideation, &quot;1&quot; meaning a wish t be dead, &quot;2&quot; meaning non-specific active suicidal thoughts, &quot;3&quot; meaning active suicidal ideation with any methods but no plan or intent, &quot;4&quot; meaning active suicidal ideation with some intent but no specific plan, and &quot;5&quot; meaning active suicidal ideation with intent and a specific plan</description>
          <population>all evaluable randomized participants</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5447" spread="0.0869"/>
                    <measurement group_id="O2" value="0.8067" spread="0.0875"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Dysfunctional Beliefs and Attitudes About Sleep</title>
        <description>The Dysfunctional Beliefs and Attitudes About Sleep scale has 16 items and is self administered. Each item is scored 0-10. The total score is an average of the scores of the 16 items. Hence the range of the total score is also 0-10, with higher scores indicating greater dysfunctional beliefs about sleep</description>
        <time_frame>8 weeks of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Zolpidem-CR</title>
            <description>Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Dysfunctional Beliefs and Attitudes About Sleep</title>
          <description>The Dysfunctional Beliefs and Attitudes About Sleep scale has 16 items and is self administered. Each item is scored 0-10. The total score is an average of the scores of the 16 items. Hence the range of the total score is also 0-10, with higher scores indicating greater dysfunctional beliefs about sleep</description>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.03" spread="0.171"/>
                    <measurement group_id="O2" value="6.07" spread="0.171"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disturbing Dreams and Nightmares Severity Index (DDNSI)</title>
        <description>This self-rated scale has 5 items, with asymmetric weighting of each item. The range of the total score is 0-37, with higher scores indicating worse nightmares</description>
        <time_frame>8 weeks of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Zolpidem-CR</title>
            <description>Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Disturbing Dreams and Nightmares Severity Index (DDNSI)</title>
          <description>This self-rated scale has 5 items, with asymmetric weighting of each item. The range of the total score is 0-37, with higher scores indicating worse nightmares</description>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.74" spread="0.710"/>
                    <measurement group_id="O2" value="6.44" spread="0.718"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Beck Hopelessness Scale (BHS)</title>
        <description>The Beck Hopelessness Scale is self administered and has 20 'true/false' choices. Some items are reversed scored. The range of scores for the total is 0-20, with higher scores indicating greater hopelessness</description>
        <time_frame>8 weeks of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Zolpidem-CR</title>
            <description>Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Beck Hopelessness Scale (BHS)</title>
          <description>The Beck Hopelessness Scale is self administered and has 20 'true/false' choices. Some items are reversed scored. The range of scores for the total is 0-20, with higher scores indicating greater hopelessness</description>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.40" spread="0.58"/>
                    <measurement group_id="O2" value="9.63" spread="0.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hamilton Rating Scale for Depression (HAM-D)</title>
        <description>This version of the Hamilton Rating Scale for Depression uses 24 items, with a possible total score ranging from 0-74, with higher scores indicating worse depression</description>
        <time_frame>8 weeks of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Zolpidem-CR</title>
            <description>Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Hamilton Rating Scale for Depression (HAM-D)</title>
          <description>This version of the Hamilton Rating Scale for Depression uses 24 items, with a possible total score ranging from 0-74, with higher scores indicating worse depression</description>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.93" spread="0.87"/>
                    <measurement group_id="O2" value="15.89" spread="0.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Insomnia Severity Index (ISI)</title>
        <description>The Insomnia Severity Index is self rated. It has 7 items, each scored 0-4. Therefore the range of scores is 0-28, with higher scores indicating worse insomnia</description>
        <time_frame>8 weeks of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Zolpidem-CR</title>
            <description>Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Insomnia Severity Index (ISI)</title>
          <description>The Insomnia Severity Index is self rated. It has 7 items, each scored 0-4. Therefore the range of scores is 0-28, with higher scores indicating worse insomnia</description>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.28" spread="0.62"/>
                    <measurement group_id="O2" value="13.72" spread="0.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Basis-32 - the Daily Living and Role Functioning (DLRF) Subscale</title>
        <description>This is one of the subscales of the Basis 32. It is self-administered. This subscale has 7 items, each scored 0-4. The totals score is an average of the scores of these 7 items. Higher scores indicate more difficulty with daily living and role functioning.</description>
        <time_frame>8 weeks of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Zolpidem-CR</title>
            <description>Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Basis-32 - the Daily Living and Role Functioning (DLRF) Subscale</title>
          <description>This is one of the subscales of the Basis 32. It is self-administered. This subscale has 7 items, each scored 0-4. The totals score is an average of the scores of these 7 items. Higher scores indicate more difficulty with daily living and role functioning.</description>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.51" spread="0.102"/>
                    <measurement group_id="O2" value="1.60" spread="0.102"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Actigraphy</title>
        <description>This device measures arm motion over time, reported as &quot;average actigraphic activity Level&quot;. The scale is reported as a continuous measure ranging from 0-200, and reported as the average score for each hour for all 24-hours of the day. Higher score represent greater c=activity at that point in time</description>
        <time_frame>8 weeks of treatment</time_frame>
        <population>participants with depression, insomnia, and suicidality</population>
        <group_list>
          <group group_id="O1">
            <title>Scale for Suicide Ideation Score Greater Than or Equal to 6</title>
            <description>Participants with a baseline Scale for Suicide Ideation Score Greater than or Equal to 6</description>
          </group>
          <group group_id="O2">
            <title>Scale for Suicide Ideation Score Less Than 6</title>
            <description>Participants with Scale for Suicide Ideation Score less than 6</description>
          </group>
        </group_list>
        <measure>
          <title>Actigraphy</title>
          <description>This device measures arm motion over time, reported as &quot;average actigraphic activity Level&quot;. The scale is reported as a continuous measure ranging from 0-200, and reported as the average score for each hour for all 24-hours of the day. Higher score represent greater c=activity at that point in time</description>
          <population>participants with depression, insomnia, and suicidality</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="150" spread="30"/>
                    <measurement group_id="O2" value="170" spread="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>8 weeks randomized care and 2 weeks of follow up after the end of randomized care</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Zolpidem-CR</title>
          <description>Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks&#xD;
Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>pregnancy then miscarriage</sub_title>
                <description>Despite being cautioned about the need for birth-control, a female participant nevertheless became pregnant (by her report), and shortly thereafter miscarried (by her report). She had a history of multiple prior miscarriages.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="31" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="37" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>nausea and diarrhea</sub_title>
                <counts group_id="E1" events="14" subjects_affected="9" subjects_at_risk="51"/>
                <counts group_id="E2" events="14" subjects_affected="9" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Other</sub_title>
                <counts group_id="E1" events="14" subjects_affected="4" subjects_at_risk="51"/>
                <counts group_id="E2" events="28" subjects_affected="13" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="9" subjects_affected="6" subjects_at_risk="51"/>
                <counts group_id="E2" events="11" subjects_affected="6" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>cold symptoms and flu</sub_title>
                <counts group_id="E1" events="21" subjects_affected="12" subjects_at_risk="51"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="52"/>
              </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>William Vaughn McCall</name_or_title>
      <organization>Medical College of Georgia; Augusta University</organization>
      <phone>706-721-6719</phone>
      <email>WMCCALL@augusta.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/NCT01689909
org study id: 1R01MH095776-01A1
secondary id: 1R01MH095776
nct id: NCT01689909
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Epidemiologic reports have linked insomnia to suicidal ideation and suicide death. However,
      no studies have determined whether treating insomnia decreases the risk of suicidality. We
      have new data indicating that (1) the link between insomnia and suicidal ideation holds true
      in clinical trials of depressed insomniacs, (2) dysfunctional cognitions about sleep are
      related to suicidal ideas, and (3) treatment of insomnia with hypnotics leads to a reduction
      of suicidal ideation. We now propose to test whether cautious use of hypnotics in suicidal,
      depressed insomniacs may reduce suicide risk in a multi-site clinical trial.
Primary Aim: We will assess the effect of treating insomnia with hypnotic medication on the
      intensity of suicidal ideation in depressed outpatients with insomnia and suicidal ideation.

      -Hypothesis 1. Treatment of depressed, insomniac and suicidal outpatients with open-label
      fluoxetine (FLX) and blinded zolpidem controlled release (ZOL) will reduce suicidal ideation
      more than treatment with FLX and blinded placebo.

      Secondary Aim: We will examine whether reduced suicidal ideation in depressed insomniacs is
      mediated through reduced dysfunctional beliefs about sleep, reduced hopelessness, or fewer
      nightmares.

        -  Hypothesis 2a. Reduction in suicidal ideation will be mediated through reductions in
           dysfunctional beliefs about sleep.

        -  Hypothesis 2b. Reduction in suicidal ideation will be mediated through reductions in
           hopelessness.

        -  Hypothesis 2c. Reduction in suicidal ideation is mediated through fewer nightmares.

      Tertiary Aim: We will confirm findings from our prior pilot studies that treatment of
      insomnia in depressed insomniacs leads to improvements in health-related quality of life,
      especially in women.

      Exploratory Aim: We will archive actigraphy data to permit future examination to confirm our
      preliminary data that actigraphic activity decreases as suicidal ideation resolves.

      Overview of the Need for and Management of a Collaborative Application: The sample sizes
      required to satisfy the Aims are relatively large, necessitating the pooled recruiting
      resources of 3 sites. Georgia Regents University (GRU) will serve both as the
      coordinating/data management site, as well as a recruiting site, with Duke and Wisconsin as
      recruiting sites. Project management will be coordinated through an Executive Committee of
      site principal investigators, under the supervision of a Data and Safety Monitoring Board.

      Impact on the Field: This application has the potential to change providers' practice in the
      approach to treating insomnia in depressed patients with mild-moderate suicidal ideation. It
      may also reveal the mechanisms whereby insomnia increases the risk for suicidal ideation and
      behavior, and begin to examine whether there is an actigraphic "signature" for reductions in
      suicidal ideation. When these lessons are applied to the clinical world, they can be applied
      with low cost.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Scale for Suicide Ideation Index (SSI)
time frame: Over 8 weeks of treatment
description: This is the total score for the Scale for Suicide Ideation. It has 19 items, each scored 0-2, for a maximum of 38 points. Higher scores indicate worse suicidal ideation
measure: Columbia Suicide Severity Rating Scale (C-SSRS): the Suicidal Ideation Scale
time frame: 8 weeks of treatment
description: The suicide ideation scale of the C-SSRS is rated 0-5, with "0" meaning no suicidal ideation, "1" meaning a wish t be dead, "2" meaning non-specific active suicidal thoughts, "3" meaning active suicidal ideation with any methods but no plan or intent, "4" meaning active suicidal ideation with some intent but no specific plan, and "5" meaning active suicidal ideation with intent and a specific plan
measure: Dysfunctional Beliefs and Attitudes About Sleep
time frame: 8 weeks of treatment
description: The Dysfunctional Beliefs and Attitudes About Sleep scale has 16 items and is self administered. Each item is scored 0-10. The total score is an average of the scores of the 16 items. Hence the range of the total score is also 0-10, with higher scores indicating greater dysfunctional beliefs about sleep
measure: Disturbing Dreams and Nightmares Severity Index (DDNSI)
time frame: 8 weeks of treatment
description: This self-rated scale has 5 items, with asymmetric weighting of each item. The range of the total score is 0-37, with higher scores indicating worse nightmares
measure: Beck Hopelessness Scale (BHS)
time frame: 8 weeks of treatment
description: The Beck Hopelessness Scale is self administered and has 20 'true/false' choices. Some items are reversed scored. The range of scores for the total is 0-20, with higher scores indicating greater hopelessness
measure: Hamilton Rating Scale for Depression (HAM-D)
time frame: 8 weeks of treatment
description: This version of the Hamilton Rating Scale for Depression uses 24 items, with a possible total score ranging from 0-74, with higher scores indicating worse depression
measure: Insomnia Severity Index (ISI)
time frame: 8 weeks of treatment
description: The Insomnia Severity Index is self rated. It has 7 items, each scored 0-4. Therefore the range of scores is 0-28, with higher scores indicating worse insomnia
measure: Basis-32 - the Daily Living and Role Functioning (DLRF) Subscale
time frame: 8 weeks of treatment
description: This is one of the subscales of the Basis 32. It is self-administered. This subscale has 7 items, each scored 0-4. The totals score is an average of the scores of these 7 items. Higher scores indicate more difficulty with daily living and role functioning.
measure: Actigraphy
time frame: 8 weeks of treatment
description: This device measures arm motion over time, reported as "average actigraphic activity Level". The scale is reported as a continuous measure ranging from 0-200, and reported as the average score for each hour for all 24-hours of the day. Higher score represent greater c=activity at that point in time
arm group label: Zolpidem-CR
arm group type: Active Comparator
description: Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks
intervention type: Drug
intervention name: Zolpidem-CR
description: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks
arm group label: Zolpidem-CR
other name: Ambien CR
intervention type: Drug
intervention name: Placebo
description: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: William V McCall, MD, MS
role: Principal Investigator
affiliation: Augusta University
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Sleep Initiation and Maintenance Disorders
mesh term: Depression
mesh term: Suicidal Ideation
mesh term: Zolpidem
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 