<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/NCT01700829</url>
  </required_header>
  <id_info>
    <org_study_id>#6598</org_study_id>
    <secondary_id>R01MH096784</secondary_id>
    <nct_id>NCT01700829</nct_id>
  </id_info>
  <brief_title>Ketamine in the Treatment of Suicidal Depression</brief_title>
  <official_title>Ketamine vs. Midazolam: Testing Rapid Relief of Suicide Risk in Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>New York State Psychiatric Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>New York State Psychiatric Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to compare the effectiveness of two medications, Ketamine and&#xD;
      Midazolam, for rapidly relieving suicidal thoughts in people suffering from depression.&#xD;
&#xD;
      The first drug, Ketamine, is an experimental antidepressant that early studies have shown may&#xD;
      quickly reduce suicidal thoughts, but we are not sure how well it may work. Midazolam, the&#xD;
      comparison drug, is not thought to reduce depression or suicidal thoughts.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients currently taking psychiatric medications may continue them during the study.&#xD;
      However, if a patient is taking a benzodiazepine (such as Ativan, Klonopin, or Xanax), they&#xD;
      will be able to take up to 2mg per day of Lorazepam during the week before the infusion, but&#xD;
      none will be permitted in the 24 hours pre-infusion. Also, Zolpidem (Ambien) will not be&#xD;
      permitted in the 24 hours pre-infusion. If a person chooses to participate, their dose of&#xD;
      benzodiazepine may need to be reduced so that they can do without it during the 24 hours&#xD;
      pre-infusion.&#xD;
&#xD;
      Depressed participants are randomly assigned to receive a single dose of Ketamine(0.5 mg/kg)&#xD;
      or Midazolam (0.02 mg/kg), which is given slowly, in a vein, over about 40 minutes. The study&#xD;
      is &quot;double-blind,&quot; meaning patients and study staff will not know which medication is in the&#xD;
      infusion.&#xD;
&#xD;
      If a patient does not respond to the first infusion, and s/he received Midazolam, then s/he&#xD;
      will be offered the option of a second infusion, this time with Ketamine (0.5 mg/kg). S/he&#xD;
      will then start treatment with a standard antidepressant, unless s/he is not already taking&#xD;
      one.&#xD;
&#xD;
      After the infusion(s), participants will have weekly research interviews for 6 weeks to&#xD;
      monitor response.&#xD;
&#xD;
      If a patient does have a sufficient infusion response, and s/he is not already taking an&#xD;
      antidepressant, then s/he will receive 6-weeks antidepressant research treatment with&#xD;
      Sertraline, Fluoxetine, Paroxetine, or Escitalopram, followed by open clinical treatment.&#xD;
      However, if s/he is already taking an antidepressant, then s/he will receive open treatment.&#xD;
      If s/he does not have a sufficient infusion response, then s/he will receive open treatment.&#xD;
&#xD;
      Participation in this study requires a brief inpatient stay, at no cost, at the New York&#xD;
      State Psychiatric Institute (NYSPI).&#xD;
&#xD;
      Eligible participants enrolled in this study will be offered medication management visits at&#xD;
      no cost for a total of up to 6 months from the date of enrollment combining inpatient and&#xD;
      outpatient treatment. Study medications (Sertraline, Fluoxetine, Paroxetine, Escitalopram,&#xD;
      Lorazepam, Zolpidem) will be at no cost during the 6 months. The study will not provide other&#xD;
      medications at no cost.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2012</start_date>
  <completion_date type="Actual">July 31, 2017</completion_date>
  <primary_completion_date type="Actual">January 12, 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>Change in Scale for Suicidal Ideation</measure>
    <time_frame>Day 1 (24 hours) post-treatment</time_frame>
    <description>Change in suicidal ideation in depressed patients with moderate to severe suicidal thoughts from the pre-infusion baseline to 24 hours after the infusion with ketamine or midazolam, a sedative not known to reduce suicidal ideation, measured with Beck Scale for Suicidal Ideation - clinician rated version. This scale has 19 items scaled 0 (least severe) to 2 (most severe) and a potential score ranging from 0 to 38, with higher score indicating greater severity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Saliva Cortisol Awakening Response (CAR).</measure>
    <time_frame>Cort2 - Cort1 = (Day 1 30-mins post-awakening cortisol) - (Day 1 awakening cortisol)</time_frame>
    <description>On the mornings of an infusion day and on post-treatment day1, participants used salivettes (Sarstedt AG &amp; Co.) to provide saliva samples upon awakening (Cort1) and 30 minutes later (Cort2) to measure cortisol awakening response (CAR) = (Cort2 - Cort1).&#xD;
Differences between the midazolam and ketamine groups were tested using an analysis of covariance (ANCOVA) model of the change in CAR from baseline to day1, with treatment group and baseline measurement of the outcome variable as predictors.&#xD;
Range from 0.1 to 12.5 ng/ml and lower means less stress response, higher means greater stress response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropsychological Effects</measure>
    <time_frame>Baseline and Day 1</time_frame>
    <description>The average Z-scores reported below are the average of the Z-scores for all tests administered. The Z-scores for each test were based on published normative data and normative data available in our laboratory. The population mean for a Z-score is zero, with a SD of 1, thus scores below zero would indicate performance below the population norm; a score close to zero indicates performance close to the population norm (or a normalizing of performance).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">82</enrollment>
  <condition>Major Depressive Disorder</condition>
  <condition>Suicidal Ideation</condition>
  <arm_group>
    <arm_group_label>Midazolam</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>0.02 mg/kg, I.V. (in the vein)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ketamine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>0.5 mg/kg, I.V. (in the vein)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>Single dose of 0.5 mg/kg of ketamine given intravenously (in the vein) over 40 minutes</description>
    <arm_group_label>Ketamine</arm_group_label>
    <other_name>Ketalar</other_name>
    <other_name>Ketamine Hydrochloride Injection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam</intervention_name>
    <description>Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes</description>
    <arm_group_label>Midazolam</arm_group_label>
    <other_name>Midazolam Injection</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        INCLUSION CRITERIA:&#xD;
&#xD;
          -  Unipolar depression with current major depressive episode (MDE). Participants may be&#xD;
             psychiatric medication-free, or if on psychiatric medication, not responding&#xD;
             adequately given current MDE with suicidal ideation (See 2).&#xD;
&#xD;
          -  Moderate to severe suicidal ideation&#xD;
&#xD;
          -  18-65 years old&#xD;
&#xD;
          -  Participants must agree to a voluntary admission to an inpatient research unit at the&#xD;
             New York State Psychiatric Institute (NYSPI)for the infusion(s), for a brief stay, or&#xD;
             longer if clinically necessary.&#xD;
&#xD;
          -  Pre-menopausal female participants of child-bearing potential must be willing to use&#xD;
             an acceptable form of birth control during study participation such as condoms,&#xD;
             diaphragm, or oral contraceptive pills.&#xD;
&#xD;
          -  Able to provide informed consent&#xD;
&#xD;
          -  Participants 61-65 years old must score a 25 or higher on the Mini-Mental State&#xD;
             Examination (MMSE) at screening.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Unstable medical condition or neurological illness, including baseline hypertension&#xD;
             (BP&gt;140/90) or significant history of cardiovascular illness.&#xD;
&#xD;
          -  Significant ECG abnormality&#xD;
&#xD;
          -  Pregnant or lactating&#xD;
&#xD;
          -  Diagnosis of bipolar disorder or psychotic disorder&#xD;
&#xD;
          -  Contraindication to any study treatment.&#xD;
&#xD;
          -  Inadequate understanding of English.&#xD;
&#xD;
          -  Prior ineffective trial of or adverse reaction to Ketamine or Midazolam.&#xD;
&#xD;
          -  Opiate use greater than total daily dose of 20mg Oxycodone or equivalent during the 3&#xD;
             days pre-infusion.&#xD;
&#xD;
          -  A diagnosis of sleep apnea.&#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>Michael F. Grunebaum, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia University/New York State Psychiatric Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Columbia University/New York State Psychiatric Institute</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://sites.google.com/site/ketamineinsuicidaldepression/</url>
    <description>Additional Information</description>
  </link>
  <link>
    <url>http://abclocal.go.com/wabc/story?section=news/health&amp;id=8975642</url>
    <description>Channel 7 NYC Story about Ketamine Research at Columbia University Medical Center</description>
  </link>
  <link>
    <url>http://www.columbiapsychiatry.org/mind/</url>
    <description>MIND Clinic for Mood and Personality Disorders</description>
  </link>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>October 2, 2012</study_first_submitted>
  <study_first_submitted_qc>October 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 4, 2012</study_first_posted>
  <results_first_submitted>March 12, 2019</results_first_submitted>
  <results_first_submitted_qc>March 10, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 11, 2020</results_first_posted>
  <last_update_submitted>March 10, 2020</last_update_submitted>
  <last_update_submitted_qc>March 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>New York State Psychiatric Institute</investigator_affiliation>
    <investigator_full_name>Michael Grunebaum, MD</investigator_full_name>
    <investigator_title>Assistant Professor of Clinical Psychiatry</investigator_title>
  </responsible_party>
  <keyword>Ketamine</keyword>
  <keyword>Midazolam</keyword>
  <keyword>Major Depressive Disorder</keyword>
  <keyword>Suicidal ideation</keyword>
  <keyword>Suicide</keyword>
  <keyword>Depression</keyword>
  <keyword>Treatment</keyword>
  <keyword>Ketamine Treatment</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>
    <mesh_term>Suicidal Ideation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>Ketamine</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 6, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/29/NCT01700829/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Midazolam</title>
          <description>0.02 mg/kg, I.V. (in the vein)&#xD;
Midazolam: Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes</description>
        </group>
        <group group_id="P2">
          <title>Ketamine</title>
          <description>0.5 mg/kg, I.V. (in the vein)&#xD;
Ketamine: Single dose of 0.5 mg/kg of ketamine given intravenously (in the vein) over 40 minutes</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="41"/>
                <participants group_id="P2" count="41"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="40"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Midazolam</title>
          <description>0.02 mg/kg, I.V. (in the vein)&#xD;
Midazolam: Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes</description>
        </group>
        <group group_id="B2">
          <title>Ketamine</title>
          <description>0.5 mg/kg, I.V. (in the vein)&#xD;
Ketamine: Single dose of 0.5 mg/kg of ketamine given intravenously (in the vein) over 40 minutes</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="40"/>
            <count group_id="B2" value="40"/>
            <count group_id="B3" value="80"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40.7" spread="13.1"/>
                    <measurement group_id="B2" value="38.4" spread="13.2"/>
                    <measurement group_id="B3" value="39.5" spread="13.1"/>
                  </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="26"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="32"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="79"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                  </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="39"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="74"/>
                  </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="40"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Scale for Suicidal Ideation</title>
          <description>The clinician-rated version of the Beck Scale for Suicidal Ideation was used to assess current severity of suicidal ideation and planning with 19 items scaled from 0 (least severe) to 2 (most severe), and a possible total score ranging from 0 to 38..</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="15.7" spread="6.9"/>
                    <measurement group_id="B2" value="14.3" spread="6.3"/>
                    <measurement group_id="B3" value="14.98" spread="6.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Scale for Suicidal Ideation</title>
        <description>Change in suicidal ideation in depressed patients with moderate to severe suicidal thoughts from the pre-infusion baseline to 24 hours after the infusion with ketamine or midazolam, a sedative not known to reduce suicidal ideation, measured with Beck Scale for Suicidal Ideation - clinician rated version. This scale has 19 items scaled 0 (least severe) to 2 (most severe) and a potential score ranging from 0 to 38, with higher score indicating greater severity.</description>
        <time_frame>Day 1 (24 hours) post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Midazolam</title>
            <description>Midazolam: Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes</description>
          </group>
          <group group_id="O2">
            <title>Ketamine</title>
            <description>Ketamine: Single dose of 0.5 mg/kg of ketamine given intravenously (in the vein) over 40 minutes</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Scale for Suicidal Ideation</title>
          <description>Change in suicidal ideation in depressed patients with moderate to severe suicidal thoughts from the pre-infusion baseline to 24 hours after the infusion with ketamine or midazolam, a sedative not known to reduce suicidal ideation, measured with Beck Scale for Suicidal Ideation - clinician rated version. This scale has 19 items scaled 0 (least severe) to 2 (most severe) and a potential score ranging from 0 to 38, with higher score indicating greater severity.</description>
          <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="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.66" spread="0.93"/>
                    <measurement group_id="O2" value="-8.62" spread="0.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Saliva Cortisol Awakening Response (CAR).</title>
        <description>On the mornings of an infusion day and on post-treatment day1, participants used salivettes (Sarstedt AG &amp; Co.) to provide saliva samples upon awakening (Cort1) and 30 minutes later (Cort2) to measure cortisol awakening response (CAR) = (Cort2 - Cort1).&#xD;
Differences between the midazolam and ketamine groups were tested using an analysis of covariance (ANCOVA) model of the change in CAR from baseline to day1, with treatment group and baseline measurement of the outcome variable as predictors.&#xD;
Range from 0.1 to 12.5 ng/ml and lower means less stress response, higher means greater stress response.</description>
        <time_frame>Cort2 - Cort1 = (Day 1 30-mins post-awakening cortisol) - (Day 1 awakening cortisol)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Midazolam</title>
            <description>Midazolam: Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes</description>
          </group>
          <group group_id="O2">
            <title>Ketamine</title>
            <description>Ketamine: Single dose of 0.5 mg/kg of ketamine given intravenously (in the vein) over 40 minutes</description>
          </group>
        </group_list>
        <measure>
          <title>Saliva Cortisol Awakening Response (CAR).</title>
          <description>On the mornings of an infusion day and on post-treatment day1, participants used salivettes (Sarstedt AG &amp; Co.) to provide saliva samples upon awakening (Cort1) and 30 minutes later (Cort2) to measure cortisol awakening response (CAR) = (Cort2 - Cort1).&#xD;
Differences between the midazolam and ketamine groups were tested using an analysis of covariance (ANCOVA) model of the change in CAR from baseline to day1, with treatment group and baseline measurement of the outcome variable as predictors.&#xD;
Range from 0.1 to 12.5 ng/ml and lower means less stress response, higher means greater stress response.</description>
          <units>log(ng/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline awakening</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.94" spread="0.61"/>
                    <measurement group_id="O2" value="0.47" spread="1.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline 30 mins post-awakening</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.29" spread="0.53"/>
                    <measurement group_id="O2" value="0.88" spread="1.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day1 awakening</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.77" spread="0.76"/>
                    <measurement group_id="O2" value="0.74" spread="0.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day1 30 minutes post-awakening</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.19" spread="0.74"/>
                    <measurement group_id="O2" value="1.06" spread="0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Neuropsychological Effects</title>
        <description>The average Z-scores reported below are the average of the Z-scores for all tests administered. The Z-scores for each test were based on published normative data and normative data available in our laboratory. The population mean for a Z-score is zero, with a SD of 1, thus scores below zero would indicate performance below the population norm; a score close to zero indicates performance close to the population norm (or a normalizing of performance).</description>
        <time_frame>Baseline and Day 1</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Midazolam</title>
            <description>Midazolam: Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes</description>
          </group>
          <group group_id="O2">
            <title>Ketamine</title>
            <description>Ketamine: Single dose of 0.5 mg/kg of ketamine given intravenously (in the vein) over 40 minutes</description>
          </group>
        </group_list>
        <measure>
          <title>Neuropsychological Effects</title>
          <description>The average Z-scores reported below are the average of the Z-scores for all tests administered. The Z-scores for each test were based on published normative data and normative data available in our laboratory. The population mean for a Z-score is zero, with a SD of 1, thus scores below zero would indicate performance below the population norm; a score close to zero indicates performance close to the population norm (or a normalizing of performance).</description>
          <units>score 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="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-infusion overall neuropsych performance</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.252" spread="0.096"/>
                    <measurement group_id="O2" value="-0.306" spread="0.096"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day1 post-infusion overall neuropsych performance</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.146" spread="0.106"/>
                    <measurement group_id="O2" value="-0.01" spread="0.106"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected for the 24 hour primary outcome study period.</time_frame>
      <desc>For the other (not including serious) adverse events, the total numbers without specific types, are reported here, with further detail available in the published paper.</desc>
      <group_list>
        <group group_id="E1">
          <title>Midazolam</title>
          <description>0.02 mg/kg, I.V. (in the vein)&#xD;
Midazolam: Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes</description>
        </group>
        <group group_id="E2">
          <title>Ketamine</title>
          <description>0.5 mg/kg, I.V. (in the vein)&#xD;
Ketamine: Single dose of 0.5 mg/kg of ketamine given intravenously (in the vein) over 40 minutes</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>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="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>medical illness unrelated to study</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Inpatient admission for suicidal ideation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>overdose</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="40"/>
              </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="12" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Subjects with any event</sub_title>
                <counts group_id="E1" events="13" subjects_affected="12" subjects_at_risk="40"/>
                <counts group_id="E2" events="11" subjects_affected="10" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Michael Grunebaum, MD</name_or_title>
      <organization>NY State Psychiatric Institute-Columbia University Medical Center</organization>
      <phone>646-774-7573</phone>
      <email>michael.grunebaum@nyspi.columbia.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/NCT01700829
org study id: #6598
secondary id: R01MH096784
nct id: NCT01700829
lead sponsor: 
collaborator: 
has dmc: Yes
This study is designed to compare the effectiveness of two medications, Ketamine and
      Midazolam, for rapidly relieving suicidal thoughts in people suffering from depression.

      The first drug, Ketamine, is an experimental antidepressant that early studies have shown may
      quickly reduce suicidal thoughts, but we are not sure how well it may work. Midazolam, the
      comparison drug, is not thought to reduce depression or suicidal thoughts.
Patients currently taking psychiatric medications may continue them during the study.
      However, if a patient is taking a benzodiazepine (such as Ativan, Klonopin, or Xanax), they
      will be able to take up to 2mg per day of Lorazepam during the week before the infusion, but
      none will be permitted in the 24 hours pre-infusion. Also, Zolpidem (Ambien) will not be
      permitted in the 24 hours pre-infusion. If a person chooses to participate, their dose of
      benzodiazepine may need to be reduced so that they can do without it during the 24 hours
      pre-infusion.

      Depressed participants are randomly assigned to receive a single dose of Ketamine(0.5 mg/kg)
      or Midazolam (0.02 mg/kg), which is given slowly, in a vein, over about 40 minutes. The study
      is "double-blind," meaning patients and study staff will not know which medication is in the
      infusion.

      If a patient does not respond to the first infusion, and s/he received Midazolam, then s/he
      will be offered the option of a second infusion, this time with Ketamine (0.5 mg/kg). S/he
      will then start treatment with a standard antidepressant, unless s/he is not already taking
      one.

      After the infusion(s), participants will have weekly research interviews for 6 weeks to
      monitor response.

      If a patient does have a sufficient infusion response, and s/he is not already taking an
      antidepressant, then s/he will receive 6-weeks antidepressant research treatment with
      Sertraline, Fluoxetine, Paroxetine, or Escitalopram, followed by open clinical treatment.
      However, if s/he is already taking an antidepressant, then s/he will receive open treatment.
      If s/he does not have a sufficient infusion response, then s/he will receive open treatment.

      Participation in this study requires a brief inpatient stay, at no cost, at the New York
      State Psychiatric Institute (NYSPI).

      Eligible participants enrolled in this study will be offered medication management visits at
      no cost for a total of up to 6 months from the date of enrollment combining inpatient and
      outpatient treatment. Study medications (Sertraline, Fluoxetine, Paroxetine, Escitalopram,
      Lorazepam, Zolpidem) will be at no cost during the 6 months. The study will not provide other
      medications at no cost.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Scale for Suicidal Ideation
time frame: Day 1 (24 hours) post-treatment
description: Change in suicidal ideation in depressed patients with moderate to severe suicidal thoughts from the pre-infusion baseline to 24 hours after the infusion with ketamine or midazolam, a sedative not known to reduce suicidal ideation, measured with Beck Scale for Suicidal Ideation - clinician rated version. This scale has 19 items scaled 0 (least severe) to 2 (most severe) and a potential score ranging from 0 to 38, with higher score indicating greater severity.
measure: Saliva Cortisol Awakening Response (CAR).
time frame: Cort2 - Cort1 = (Day 1 30-mins post-awakening cortisol) - (Day 1 awakening cortisol)
description: On the mornings of an infusion day and on post-treatment day1, participants used salivettes (Sarstedt AG & Co.) to provide saliva samples upon awakening (Cort1) and 30 minutes later (Cort2) to measure cortisol awakening response (CAR) = (Cort2 - Cort1).
Differences between the midazolam and ketamine groups were tested using an analysis of covariance (ANCOVA) model of the change in CAR from baseline to day1, with treatment group and baseline measurement of the outcome variable as predictors.
Range from 0.1 to 12.5 ng/ml and lower means less stress response, higher means greater stress response.
measure: Neuropsychological Effects
time frame: Baseline and Day 1
description: The average Z-scores reported below are the average of the Z-scores for all tests administered. The Z-scores for each test were based on published normative data and normative data available in our laboratory. The population mean for a Z-score is zero, with a SD of 1, thus scores below zero would indicate performance below the population norm; a score close to zero indicates performance close to the population norm (or a normalizing of performance).
arm group label: Midazolam
arm group type: Active Comparator
description: 0.02 mg/kg, I.V. (in the vein)
arm group label: Ketamine
arm group type: Active Comparator
description: 0.5 mg/kg, I.V. (in the vein)
intervention type: Drug
intervention name: Ketamine
description: Single dose of 0.5 mg/kg of ketamine given intravenously (in the vein) over 40 minutes
arm group label: Ketamine
other name: Ketalar
other name: Ketamine Hydrochloride Injection
intervention type: Drug
intervention name: Midazolam
description: Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes
arm group label: Midazolam
other name: Midazolam Injection
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Michael F. Grunebaum, M.D.
role: Principal Investigator
affiliation: Columbia University/New York State Psychiatric Institute
facility: 
country: United States
url: https://sites.google.com/site/ketamineinsuicidaldepression/
description: Additional Information
url: http://abclocal.go.com/wabc/story?section=news/health&id=8975642
description: Channel 7 NYC Story about Ketamine Research at Columbia University Medical Center
url: http://www.columbiapsychiatry.org/mind/
description: MIND Clinic for Mood and Personality Disorders
responsible party type: Principal Investigator
investigator affiliation: New York State Psychiatric Institute
investigator full name: Michael Grunebaum, MD
investigator title: Assistant Professor of Clinical Psychiatry
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Suicidal Ideation
mesh term: Midazolam
mesh term: Ketamine
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 