<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/NCT01703039</url>
  </required_header>
  <id_info>
    <org_study_id>2012P001841</org_study_id>
    <nct_id>NCT01703039</nct_id>
  </id_info>
  <brief_title>Riluzole Augmentation Pilot in Depression (RAPID) Trial</brief_title>
  <acronym>RAPID</acronym>
  <official_title>Riluzole Augmentation Pilot in Depression (RAPID) Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Brigham and Women's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators are doing a research study to find out if riluzole, when taken along with a&#xD;
      standard antidepressant (sertraline) can help people with major depression.&#xD;
&#xD;
      This research study will compare riluzole + sertraline to placebo + sertraline. The&#xD;
      investigators hypothesize that adding riluzole will lead to a better antidepressant response,&#xD;
      in less time, then sertraline alone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Recent attention has focused on the glutamatergic system as a new, distinct target for&#xD;
      depression treatment. Riluzole (Rilutek, Sanofi), an oral modulator of glutamate activity&#xD;
      with neuroprotective and anticonvulsant properties, is currently approved by the United&#xD;
      States Food and Drug Administration for treatment of amyotrophic lateral sclerosis (ALS).&#xD;
      Preliminary studies using riluzole to treat depression in humans are promising, though&#xD;
      larger, double-blinded controlled trials are needed.&#xD;
&#xD;
      Overall study population:&#xD;
&#xD;
      Adult outpatients with a current, untreated major depressive episode.&#xD;
&#xD;
      Disallowed therapies include: other psychotropic medications, including antipsychotics, mood&#xD;
      stabilizers, benzodiazepines, barbiturates, other sedative-hypnotics, chronic opiates, or&#xD;
      additional antidepressants, psychotherapy, electroconvulsive therapy, vagal nerve&#xD;
      stimulations therapy, transcranial magnetic stimulation therapy, or phototherapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    PI departure, slow recruitment&#xD;
  </why_stopped>
  <start_date type="Actual">January 2013</start_date>
  <completion_date type="Actual">June 2018</completion_date>
  <primary_completion_date type="Actual">June 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Change in Hamilton Depression Rating Scale (HDRS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks</measure>
    <time_frame>0 weeks-8 weeks</time_frame>
    <description>The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Patients Experiencing an Antidepressant Response (&gt;50% Reduction in HDRS) at Endpoint of 8 Weeks</measure>
    <time_frame>0 weeks-8 weeks</time_frame>
    <description>The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Patients Experiencing Remission From Depression (HDRS&lt;7) at Endpoint of 8 Weeks</measure>
    <time_frame>0 weeks-8 weeks</time_frame>
    <description>The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change in Hamilton Anxiety Rating Scale (HARS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks</measure>
    <time_frame>0 weeks-8 weeks</time_frame>
    <description>The HARS scale is a clinician rated interview scale designed to measure the signs and symptoms of anxiety. It has 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) were summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicate less anxiety.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change in Clinical Global Impression (CGI) Scale From Baseline (0 Weeks) to Endpoint at 8 Weeks</measure>
    <time_frame>0 weeks-8 weeks</time_frame>
    <description>The Clinical Global Impression Scale (CGI) is a brief clinician-rated instrument. The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-C scores range from 1 (very much improved) through to 7 (very much worse). Treatment response ratings should take account of both therapeutic efficacy and treatment-related adverse events and range from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects). Each component of the CGI is rated separately; the instrument does not yield a global score.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>sertraline + riluzole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>sertraline 100 mg po daily and riluzole 50 mg po bid</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sertraline + placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>sertraline 100 mg po daily and placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Riluzole</intervention_name>
    <arm_group_label>sertraline + riluzole</arm_group_label>
    <other_name>Rilutek</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sertraline</intervention_name>
    <arm_group_label>sertraline + placebo</arm_group_label>
    <arm_group_label>sertraline + riluzole</arm_group_label>
    <other_name>Zoloft</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>placebo</intervention_name>
    <arm_group_label>sertraline + placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults (ages 18-75) who meet DSM-IV criteria for a major depressive episode,&#xD;
&#xD;
          -  Hamilton Depression Rating Scale (HDRS) &gt;22, and&#xD;
&#xD;
          -  No antidepressant treatment for at least three weeks&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active drug or alcohol disorder in the past 3 months&#xD;
&#xD;
          -  History of psychosis, history of mania or hypomania&#xD;
&#xD;
          -  Epilepsy or history of seizures&#xD;
&#xD;
          -  Hypothyroidism&#xD;
&#xD;
          -  Congenital QTc prolongation&#xD;
&#xD;
          -  Liver disease&#xD;
&#xD;
          -  Lung disease&#xD;
&#xD;
          -  Acute suicide or homicide risk&#xD;
&#xD;
          -  Pregnant women, breastfeeding women, women of childbearing age not using contraception&#xD;
&#xD;
          -  Unstable medical illness&#xD;
&#xD;
          -  Elevated thyroid-stimulating hormone (TSH&gt;5.0mlU/L), or&#xD;
&#xD;
          -  Abnormal liver function tests (ALT&gt;50 U/L or AST&gt;50 U/L)&#xD;
&#xD;
          -  ADD / ADHD (Attention deficit hyperactivity disorder)&#xD;
&#xD;
        Disallowed therapies include: other psychotropic medications, including antipsychotics,&#xD;
        mood stabilizers, benzodiazepines, barbiturates, other sedative-hypnotics, chronic opiates,&#xD;
        or additional antidepressants, psychotherapy, electroconvulsive therapy, vagal nerve&#xD;
        stimulations therapy, transcranial magnetic stimulation therapy, or phototherapy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jessica Harder, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>October 4, 2012</study_first_submitted>
  <study_first_submitted_qc>October 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2012</study_first_posted>
  <results_first_submitted>June 24, 2019</results_first_submitted>
  <results_first_submitted_qc>August 9, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 28, 2019</results_first_posted>
  <last_update_submitted>August 9, 2019</last_update_submitted>
  <last_update_submitted_qc>August 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Jessica Harder</investigator_full_name>
    <investigator_title>Physician</investigator_title>
  </responsible_party>
  <keyword>Major Depression</keyword>
  <keyword>Major Depressive Disorder</keyword>
  <keyword>Depression</keyword>
  <keyword>Riluzole</keyword>
  <keyword>Glutamate</keyword>
  <keyword>Sertraline</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Riluzole</mesh_term>
    <mesh_term>Sertraline</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>May 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/39/NCT01703039/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Sertraline + Riluzole</title>
          <description>sertraline 100 mg po daily and riluzole 50 mg po bid&#xD;
Riluzole&#xD;
Sertraline</description>
        </group>
        <group group_id="P2">
          <title>Sertraline + Placebo</title>
          <description>sertraline 100 mg po daily and placebo&#xD;
Sertraline&#xD;
placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Sertraline + Riluzole</title>
          <description>sertraline 100 mg po daily and riluzole 50 mg po bid&#xD;
Riluzole&#xD;
Sertraline</description>
        </group>
        <group group_id="B2">
          <title>Sertraline + Placebo</title>
          <description>sertraline 100 mg po daily and placebo&#xD;
Sertraline&#xD;
placebo</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="6"/>
            <count group_id="B2" value="7"/>
            <count group_id="B3" value="13"/>
          </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="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </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="53.83" spread="14.88"/>
                    <measurement group_id="B2" value="52.86" spread="7.71"/>
                    <measurement group_id="B3" value="53.31" spread="11.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </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="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hamilton Depression Rating Scale (HDRS)</title>
          <description>Scale measures presence and severity of depression. Scale ranges from a minimum score of 0 to a maximum score of 52. Higher values represent more severe depression and a worse outcome.</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="26" spread="2.53"/>
                    <measurement group_id="B2" value="25.14" spread="2.97"/>
                    <measurement group_id="B3" value="25.54" spread="2.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hamilton Anxiety Rating Scale (HARS)</title>
          <description>Scale measures anxiety. Total highest score is 56. Higher scores indicate worse anxiety.</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="29.83" spread="7.33"/>
                    <measurement group_id="B2" value="27.14" spread="10.12"/>
                    <measurement group_id="B3" value="28.38" spread="8.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Clinical Global Impression Scale (CGI)</title>
          <description>The Clinical Global Impression (CGI) severity of illness scale rates overall severity of illness.&#xD;
CGI scores range from 1 to 7. Higher scores are worse outcomes.</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="5" spread="0.63"/>
                    <measurement group_id="B2" value="5.14" spread="0.90"/>
                    <measurement group_id="B3" value="5.08" spread="0.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Change in Hamilton Depression Rating Scale (HDRS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks</title>
        <description>The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52.</description>
        <time_frame>0 weeks-8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sertraline + Riluzole</title>
            <description>sert 100mg po daily and riluzole...</description>
          </group>
          <group group_id="O2">
            <title>Sertraline + Placebo</title>
            <description>sert 100mg po daily and placebo...</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Hamilton Depression Rating Scale (HDRS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks</title>
          <description>The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.67" spread="7.09"/>
                    <measurement group_id="O2" value="-13.43" spread="6.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.06</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients Experiencing an Antidepressant Response (&gt;50% Reduction in HDRS) at Endpoint of 8 Weeks</title>
        <description>The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52.</description>
        <time_frame>0 weeks-8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sertraline + Riluzole</title>
            <description>sertraline 100 mg po daily and riluzole 50 mg po bid&#xD;
Riluzole&#xD;
Sertraline</description>
          </group>
          <group group_id="O2">
            <title>Sertraline + Placebo</title>
            <description>sertraline 100 mg po daily and placebo&#xD;
Sertraline&#xD;
placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Experiencing an Antidepressant Response (&gt;50% Reduction in HDRS) at Endpoint of 8 Weeks</title>
          <description>The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.31</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients Experiencing Remission From Depression (HDRS&lt;7) at Endpoint of 8 Weeks</title>
        <description>The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52.</description>
        <time_frame>0 weeks-8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sertraline + Riluzole</title>
            <description>sertraline 100 mg po daily and riluzole 50 mg po bid&#xD;
Riluzole&#xD;
Sertraline</description>
          </group>
          <group group_id="O2">
            <title>Sertraline + Placebo</title>
            <description>sertraline 100 mg po daily and placebo&#xD;
Sertraline&#xD;
placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Experiencing Remission From Depression (HDRS&lt;7) at Endpoint of 8 Weeks</title>
          <description>The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.34</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change in Hamilton Anxiety Rating Scale (HARS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks</title>
        <description>The HARS scale is a clinician rated interview scale designed to measure the signs and symptoms of anxiety. It has 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) were summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicate less anxiety.</description>
        <time_frame>0 weeks-8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sertraline + Riluzole</title>
            <description>sertraline 100 mg po daily and riluzole 50 mg po bid&#xD;
Riluzole&#xD;
Sertraline</description>
          </group>
          <group group_id="O2">
            <title>Sertraline + Placebo</title>
            <description>sertraline 100 mg po daily and placebo&#xD;
Sertraline&#xD;
placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Hamilton Anxiety Rating Scale (HARS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks</title>
          <description>The HARS scale is a clinician rated interview scale designed to measure the signs and symptoms of anxiety. It has 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) were summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicate less anxiety.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.50" spread="10.88"/>
                    <measurement group_id="O2" value="-15.57" spread="7.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.27</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change in Clinical Global Impression (CGI) Scale From Baseline (0 Weeks) to Endpoint at 8 Weeks</title>
        <description>The Clinical Global Impression Scale (CGI) is a brief clinician-rated instrument. The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-C scores range from 1 (very much improved) through to 7 (very much worse). Treatment response ratings should take account of both therapeutic efficacy and treatment-related adverse events and range from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects). Each component of the CGI is rated separately; the instrument does not yield a global score.</description>
        <time_frame>0 weeks-8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sertraline + Riluzole</title>
            <description>sertraline 100 mg po daily and riluzole 50 mg po bid&#xD;
Riluzole&#xD;
Sertraline</description>
          </group>
          <group group_id="O2">
            <title>Sertraline + Placebo</title>
            <description>sertraline 100 mg po daily and placebo&#xD;
Sertraline&#xD;
placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Clinical Global Impression (CGI) Scale From Baseline (0 Weeks) to Endpoint at 8 Weeks</title>
          <description>The Clinical Global Impression Scale (CGI) is a brief clinician-rated instrument. The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-C scores range from 1 (very much improved) through to 7 (very much worse). Treatment response ratings should take account of both therapeutic efficacy and treatment-related adverse events and range from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects). Each component of the CGI is rated separately; the instrument does not yield a global score.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.67" spread="0.82"/>
                    <measurement group_id="O2" value="-2.71" spread="1.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.04</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>8 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Sertraline + Riluzole</title>
          <description>sertraline 100 mg po daily and riluzole 50 mg po bid&#xD;
Riluzole&#xD;
Sertraline</description>
        </group>
        <group group_id="E2">
          <title>Sertraline + Placebo</title>
          <description>sertraline 100 mg po daily and placebo&#xD;
Sertraline&#xD;
placebo</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="2" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Elevated Liver Function Tests (LFTs)</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
              </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. Jessica Harder</name_or_title>
      <organization>Brigham and Women's Hospital</organization>
      <phone>617-525-7919</phone>
      <email>jaharder@bwh.harvard.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/NCT01703039
org study id: 2012P001841
nct id: NCT01703039
lead sponsor: 
has dmc: Yes
The investigators are doing a research study to find out if riluzole, when taken along with a
      standard antidepressant (sertraline) can help people with major depression.

      This research study will compare riluzole + sertraline to placebo + sertraline. The
      investigators hypothesize that adding riluzole will lead to a better antidepressant response,
      in less time, then sertraline alone.
Recent attention has focused on the glutamatergic system as a new, distinct target for
      depression treatment. Riluzole (Rilutek, Sanofi), an oral modulator of glutamate activity
      with neuroprotective and anticonvulsant properties, is currently approved by the United
      States Food and Drug Administration for treatment of amyotrophic lateral sclerosis (ALS).
      Preliminary studies using riluzole to treat depression in humans are promising, though
      larger, double-blinded controlled trials are needed.

      Overall study population:

      Adult outpatients with a current, untreated major depressive episode.

      Disallowed therapies include: other psychotropic medications, including antipsychotics, mood
      stabilizers, benzodiazepines, barbiturates, other sedative-hypnotics, chronic opiates, or
      additional antidepressants, psychotherapy, electroconvulsive therapy, vagal nerve
      stimulations therapy, transcranial magnetic stimulation therapy, or phototherapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Mean Change in Hamilton Depression Rating Scale (HDRS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks
time frame: 0 weeks-8 weeks
description: The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52.
measure: Number of Patients Experiencing an Antidepressant Response (>50% Reduction in HDRS) at Endpoint of 8 Weeks
time frame: 0 weeks-8 weeks
description: The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52.
measure: Number of Patients Experiencing Remission From Depression (HDRS<7) at Endpoint of 8 Weeks
time frame: 0 weeks-8 weeks
description: The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52.
measure: Mean Change in Hamilton Anxiety Rating Scale (HARS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks
time frame: 0 weeks-8 weeks
description: The HARS scale is a clinician rated interview scale designed to measure the signs and symptoms of anxiety. It has 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) were summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicate less anxiety.
measure: Mean Change in Clinical Global Impression (CGI) Scale From Baseline (0 Weeks) to Endpoint at 8 Weeks
time frame: 0 weeks-8 weeks
description: The Clinical Global Impression Scale (CGI) is a brief clinician-rated instrument. The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-C scores range from 1 (very much improved) through to 7 (very much worse). Treatment response ratings should take account of both therapeutic efficacy and treatment-related adverse events and range from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects). Each component of the CGI is rated separately; the instrument does not yield a global score.
arm group label: sertraline + riluzole
arm group type: Experimental
description: sertraline 100 mg po daily and riluzole 50 mg po bid
arm group label: sertraline + placebo
arm group type: Active Comparator
description: sertraline 100 mg po daily and placebo
intervention type: Drug
intervention name: Riluzole
arm group label: sertraline + riluzole
other name: Rilutek
intervention type: Drug
intervention name: Sertraline
arm group label: sertraline + placebo
arm group label: sertraline + riluzole
other name: Zoloft
intervention type: Other
intervention name: placebo
arm group label: sertraline + placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jessica Harder, MD
role: Principal Investigator
affiliation: Brigham and Women's Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Jessica Harder
investigator title: Physician
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Riluzole
mesh term: Sertraline
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 