<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/NCT03256162</url>
  </required_header>
  <id_info>
    <org_study_id>01/17</org_study_id>
    <secondary_id>2016-004764-18</secondary_id>
    <nct_id>NCT03256162</nct_id>
  </id_info>
  <brief_title>Ketamine as an Adjunctive Therapy for Major Depression</brief_title>
  <acronym>KARMA-dep</acronym>
  <official_title>Ketamine as an Adjunctive Therapy for Major Depression - a Randomised Controlled Pilot Trial: The KARMA-Dep Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St Patrick's Hospital, Ireland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>St Patrick's Hospital, Ireland</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Randomised, controlled, parallel-group, pilot clinical trial of ketamine vs. midazolam as an&#xD;
      adjunctive therapy for depression. The main purpose of the pilot study is to assess trial&#xD;
      processes to help inform a future definitive trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pragmatic, randomised, controlled, parallel-group, pilot trial. Trial participants will be&#xD;
      patients admitted to St Patrick's University Hospital for treatment of a depressive episode.&#xD;
      The investigators aim to recruit up to 20 participants who will be eligible for this study&#xD;
      and randomly allocate 10 patients to each group. The participants will undergo usual&#xD;
      inpatient care as prescribed by their treating team for the index acute depressive episode.&#xD;
      Both participants and assessors will be blind to treatment allocation. Consented participants&#xD;
      will be randomly allocated in a 1:1 ratio to a four week course of either once-weekly&#xD;
      ketamine or midazolam infusions. Block randomisation will be independently performed.&#xD;
      Physical, psychotomimetic and cognitive outcomes will be monitored before, during and after&#xD;
      infusions. Blood samples will be taken at four time-points in the first infusion session and&#xD;
      before the final infusion for neuroplasticity biomarker studies. Both groups will continue&#xD;
      treatment as usual. Participates will also be followed up over a three month period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 7, 2017</start_date>
  <completion_date type="Actual">September 21, 2018</completion_date>
  <primary_completion_date type="Actual">September 21, 2018</primary_completion_date>
  <phase>Phase 1</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>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Hamilton Rating Scale for Depression-24 Item Version (HRSD-24)</measure>
    <time_frame>15 weeks</time_frame>
    <description>The HRSD assesses severity of depressive symptoms and is commonly used to measure depression severity. It was initially a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HRSD includes items on helplessness, hopelessness and worthlessness; its score range is 0-77, with higher scores reflecting greater burden of depressive symptoms.&#xD;
Response to antidepressant treatment is defined as achieving ≥60% decrease from baseline HRSD-24 and score ≤16. Remission criteria are ≥60% decrease in HRSD from baseline and score ≤10. Criteria for relapse are ≥10 point increase in HRSD-24 compared to responder baseline score plus HRSD ≥16; in addition, increase in the HRSD should be maintained one week later.&#xD;
Participants will have a baseline (T0) HRSD-24 score. This will be repeated 1 week after each of 4 once-weekly infusions (T1-4) and follow-up measures after another 5 (T9) and 11 (T15) weeks, week 15 is reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Quick Inventory of Depressive Symptoms, Self-report Version (QIDS-SR16)</measure>
    <time_frame>15 weeks</time_frame>
    <description>The QIDS-SR16 is a validated self-report measure of depressive symptoms. This consists of 16 questions rated 0-3. Its score range is 0-48, with higher scores reflecting greater burden of depressive symptoms.&#xD;
Participants will have a baseline (T0) QIDS-SR16 score. This will be repeated one week after each of four once-weekly infusions (T1-4) and follow-up measures after another five (T9) and 11 (T15) weeks. Week 15 scores are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Clinician-Administered Dissociative States Scale (CADSS)</measure>
    <time_frame>4 weeks</time_frame>
    <description>The CADSS measures dissociative symptoms. It will be administered before, during and after infusions in order to capture the range of possible subjective side effects of either agent. This consists of 23 questions and scores for each question range from 0-4. The maximum score is 92 with higher scores indicating more dissociative symptoms.&#xD;
Participants will have the CADSS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Brief Psychiatric Rating Scale (BPRS)</measure>
    <time_frame>4 weeks</time_frame>
    <description>The BPRS measures psychotomimetic effects. The investigators will use the positive symptoms subscale of the Brief Psychiatric Rating Scale. The 4-item positive symptoms subscale measures suspiciousness, hallucinations, unusual thought content, and conceptual disorganisation. Each question is scored between 0-7. The maximum score in this 4-item questionnaire is 28. Higher scores indicate more severe psychotic symptoms.&#xD;
Participants will have the BPRS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Young Mania Rating Scale (YMRS; Mood Item)</measure>
    <time_frame>4 weeks</time_frame>
    <description>Investigators will use the mood item of them YMRS to assess for psychotomimetic effects. This item is rated 0-4. The higher scores reflect elevated mood.&#xD;
Participants will have the YMRS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Patient-Rated Inventory of Side Effects (PRISE)</measure>
    <time_frame>4 weeks</time_frame>
    <description>The PRISE will be used to document other general adverse events by patients before, during and after infusions. This is a patient self-report used to qualify side effects by identifying and evaluating the tolerability of each symptom. It is a 9 item assessment of the side effects in the following symptom domains; Gastrointestinal, Heart, Skin, Nervous System, Eyes/Ears, Genital/Urinary, Sleep, Sexual Functioning, and Other. Each domain has multiple symptoms which can be endorsed. For each domain the patient rates whether or not the symptoms are tolerable or distressing. Data below represent the number of participants from which there was an endorsement of each listed event.&#xD;
Participants will have the PRISE performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Montreal Cognitive Assessment (MoCA)</measure>
    <time_frame>15 weeks</time_frame>
    <description>The MOCA was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, conceptual thinking, calculations, and orientation. It is scored out of a maximum of 30. The higher scores indicate better cognition.&#xD;
The MOCA will be performed at baseline, one day after infusions 1 and 4 and 12 weeks after the final infusion.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Major Depressive Episode</condition>
  <condition>Unipolar Depression</condition>
  <condition>Bipolar Depression</condition>
  <arm_group>
    <arm_group_label>Ketamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Midazolam</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.</description>
    <arm_group_label>Ketamine</arm_group_label>
    <other_name>Ketalar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam</intervention_name>
    <description>A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.</description>
    <arm_group_label>Midazolam</arm_group_label>
    <other_name>Hypnovel</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ≥18 years old&#xD;
&#xD;
          -  Hamilton Rating Scale for Depression-24 item version (HRSD-24) score of ≥21&#xD;
&#xD;
          -  Voluntary admission for treatment of an acute depressive episode&#xD;
&#xD;
          -  Meet Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition (DSM-V)&#xD;
             criteria for a major depressive disorder (MDD) and bipolar affective disorder (current&#xD;
             episode depression)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current involuntary admission&#xD;
&#xD;
          -  Medical condition rendering unfit for ketamine/midazolam&#xD;
&#xD;
          -  Active suicidal intention&#xD;
&#xD;
          -  Dementia&#xD;
&#xD;
          -  History of Axis 1 diagnosis other than major depression&#xD;
&#xD;
          -  Electroconvulsive Therapy (ECT) administered within the last two months&#xD;
&#xD;
          -  Alcohol/substance dependence in previous six-months&#xD;
&#xD;
          -  Pregnancy or inability to confirm use of adequate contraception during the trial&#xD;
&#xD;
          -  Breastfeeding women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Declan M McLoughlin, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St Patrick's Mental Health Services and Trinity College Dublin</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St Patrick's University Hospital</name>
      <address>
        <city>Dublin</city>
        <zip>D8</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ireland</country>
  </location_countries>
  <link>
    <url>https://www.tcd.ie/medicine/psychiatry/research/depression/</url>
    <description>Research Team Website</description>
  </link>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 21, 2017</study_first_posted>
  <results_first_submitted>January 2, 2020</results_first_submitted>
  <results_first_submitted_qc>January 15, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 18, 2020</results_first_posted>
  <last_update_submitted>January 15, 2020</last_update_submitted>
  <last_update_submitted_qc>January 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>St Patrick's Hospital, Ireland</investigator_affiliation>
    <investigator_full_name>Prof Declan McLoughlin</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>ketamine</keyword>
  <keyword>glutamate</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>Bipolar Disorder</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>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>June 13, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/62/NCT03256162/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Potential participants were those who were admitted to St Patrick's University Hospital, Dublin, for treatment of a major depressive episode (either unipolar or bipolar depression) between 06.09.17 and 12.06.18.</recruitment_details>
      <pre_assignment_details>Treatment-as-usual, by the participants' treating teams, continued throughout the entire trial.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Ketamine</title>
          <description>Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.</description>
        </group>
        <group group_id="P2">
          <title>Midazolam</title>
          <description>Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Ketamine</title>
          <description>Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.</description>
        </group>
        <group group_id="B2">
          <title>Midazolam</title>
          <description>Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.</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="13"/>
            <count group_id="B2" value="12"/>
            <count group_id="B3" value="25"/>
          </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="48.9" spread="13.1"/>
                    <measurement group_id="B2" value="52.3" spread="12.5"/>
                    <measurement group_id="B3" value="50.5" spread="12.6"/>
                  </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="8"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</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_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="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="25"/>
                  </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>The Hamilton Rating Scale for Depression-24 Item Version (HRSD-24)</title>
          <description>The HRSD assesses severity of depressive symptoms and is commonly used to measure depression severity. It was initially a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HRSD includes items on helplessness, hopelessness and worthlessness; its score range is 0-77, with higher scores reflecting greater burden of depressive symptoms.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28.4" spread="4.3"/>
                    <measurement group_id="B2" value="27.4" spread="4.3"/>
                    <measurement group_id="B3" value="27.7" spread="3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Hamilton Rating Scale for Depression-24 Item Version (HRSD-24)</title>
        <description>The HRSD assesses severity of depressive symptoms and is commonly used to measure depression severity. It was initially a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HRSD includes items on helplessness, hopelessness and worthlessness; its score range is 0-77, with higher scores reflecting greater burden of depressive symptoms.&#xD;
Response to antidepressant treatment is defined as achieving ≥60% decrease from baseline HRSD-24 and score ≤16. Remission criteria are ≥60% decrease in HRSD from baseline and score ≤10. Criteria for relapse are ≥10 point increase in HRSD-24 compared to responder baseline score plus HRSD ≥16; in addition, increase in the HRSD should be maintained one week later.&#xD;
Participants will have a baseline (T0) HRSD-24 score. This will be repeated 1 week after each of 4 once-weekly infusions (T1-4) and follow-up measures after another 5 (T9) and 11 (T15) weeks, week 15 is reported.</description>
        <time_frame>15 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ketamine</title>
            <description>Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.</description>
          </group>
          <group group_id="O2">
            <title>Midazolam</title>
            <description>Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.</description>
          </group>
        </group_list>
        <measure>
          <title>The Hamilton Rating Scale for Depression-24 Item Version (HRSD-24)</title>
          <description>The HRSD assesses severity of depressive symptoms and is commonly used to measure depression severity. It was initially a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HRSD includes items on helplessness, hopelessness and worthlessness; its score range is 0-77, with higher scores reflecting greater burden of depressive symptoms.&#xD;
Response to antidepressant treatment is defined as achieving ≥60% decrease from baseline HRSD-24 and score ≤16. Remission criteria are ≥60% decrease in HRSD from baseline and score ≤10. Criteria for relapse are ≥10 point increase in HRSD-24 compared to responder baseline score plus HRSD ≥16; in addition, increase in the HRSD should be maintained one week later.&#xD;
Participants will have a baseline (T0) HRSD-24 score. This will be repeated 1 week after each of 4 once-weekly infusions (T1-4) and follow-up measures after another 5 (T9) and 11 (T15) weeks, week 15 is reported.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.2" lower_limit="6.2" upper_limit="16.2"/>
                    <measurement group_id="O2" value="16.6" lower_limit="7.8" upper_limit="25.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Quick Inventory of Depressive Symptoms, Self-report Version (QIDS-SR16)</title>
        <description>The QIDS-SR16 is a validated self-report measure of depressive symptoms. This consists of 16 questions rated 0-3. Its score range is 0-48, with higher scores reflecting greater burden of depressive symptoms.&#xD;
Participants will have a baseline (T0) QIDS-SR16 score. This will be repeated one week after each of four once-weekly infusions (T1-4) and follow-up measures after another five (T9) and 11 (T15) weeks. Week 15 scores are reported.</description>
        <time_frame>15 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ketamine</title>
            <description>Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.</description>
          </group>
          <group group_id="O2">
            <title>Midazolam</title>
            <description>Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.</description>
          </group>
        </group_list>
        <measure>
          <title>The Quick Inventory of Depressive Symptoms, Self-report Version (QIDS-SR16)</title>
          <description>The QIDS-SR16 is a validated self-report measure of depressive symptoms. This consists of 16 questions rated 0-3. Its score range is 0-48, with higher scores reflecting greater burden of depressive symptoms.&#xD;
Participants will have a baseline (T0) QIDS-SR16 score. This will be repeated one week after each of four once-weekly infusions (T1-4) and follow-up measures after another five (T9) and 11 (T15) weeks. Week 15 scores are reported.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.1" lower_limit="5.6" upper_limit="12.6"/>
                    <measurement group_id="O2" value="11.4" lower_limit="4.9" upper_limit="18.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Clinician-Administered Dissociative States Scale (CADSS)</title>
        <description>The CADSS measures dissociative symptoms. It will be administered before, during and after infusions in order to capture the range of possible subjective side effects of either agent. This consists of 23 questions and scores for each question range from 0-4. The maximum score is 92 with higher scores indicating more dissociative symptoms.&#xD;
Participants will have the CADSS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.</description>
        <time_frame>4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ketamine</title>
            <description>Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.</description>
          </group>
          <group group_id="O2">
            <title>Midazolam</title>
            <description>Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.</description>
          </group>
        </group_list>
        <measure>
          <title>The Clinician-Administered Dissociative States Scale (CADSS)</title>
          <description>The CADSS measures dissociative symptoms. It will be administered before, during and after infusions in order to capture the range of possible subjective side effects of either agent. This consists of 23 questions and scores for each question range from 0-4. The maximum score is 92 with higher scores indicating more dissociative symptoms.&#xD;
Participants will have the CADSS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.</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="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.3" spread="7.2"/>
                    <measurement group_id="O2" value="2.5" spread="3.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Brief Psychiatric Rating Scale (BPRS)</title>
        <description>The BPRS measures psychotomimetic effects. The investigators will use the positive symptoms subscale of the Brief Psychiatric Rating Scale. The 4-item positive symptoms subscale measures suspiciousness, hallucinations, unusual thought content, and conceptual disorganisation. Each question is scored between 0-7. The maximum score in this 4-item questionnaire is 28. Higher scores indicate more severe psychotic symptoms.&#xD;
Participants will have the BPRS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.</description>
        <time_frame>4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ketamine</title>
            <description>Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.</description>
          </group>
          <group group_id="O2">
            <title>Midazolam</title>
            <description>Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.</description>
          </group>
        </group_list>
        <measure>
          <title>The Brief Psychiatric Rating Scale (BPRS)</title>
          <description>The BPRS measures psychotomimetic effects. The investigators will use the positive symptoms subscale of the Brief Psychiatric Rating Scale. The 4-item positive symptoms subscale measures suspiciousness, hallucinations, unusual thought content, and conceptual disorganisation. Each question is scored between 0-7. The maximum score in this 4-item questionnaire is 28. Higher scores indicate more severe psychotic symptoms.&#xD;
Participants will have the BPRS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.</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="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.1" spread="0.4"/>
                    <measurement group_id="O2" value="4.0" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Young Mania Rating Scale (YMRS; Mood Item)</title>
        <description>Investigators will use the mood item of them YMRS to assess for psychotomimetic effects. This item is rated 0-4. The higher scores reflect elevated mood.&#xD;
Participants will have the YMRS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.</description>
        <time_frame>4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ketamine</title>
            <description>Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.</description>
          </group>
          <group group_id="O2">
            <title>Midazolam</title>
            <description>Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.</description>
          </group>
        </group_list>
        <measure>
          <title>Young Mania Rating Scale (YMRS; Mood Item)</title>
          <description>Investigators will use the mood item of them YMRS to assess for psychotomimetic effects. This item is rated 0-4. The higher scores reflect elevated mood.&#xD;
Participants will have the YMRS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.</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="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.4"/>
                    <measurement group_id="O2" value="0.1" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Patient-Rated Inventory of Side Effects (PRISE)</title>
        <description>The PRISE will be used to document other general adverse events by patients before, during and after infusions. This is a patient self-report used to qualify side effects by identifying and evaluating the tolerability of each symptom. It is a 9 item assessment of the side effects in the following symptom domains; Gastrointestinal, Heart, Skin, Nervous System, Eyes/Ears, Genital/Urinary, Sleep, Sexual Functioning, and Other. Each domain has multiple symptoms which can be endorsed. For each domain the patient rates whether or not the symptoms are tolerable or distressing. Data below represent the number of participants from which there was an endorsement of each listed event.&#xD;
Participants will have the PRISE performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.</description>
        <time_frame>4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ketamine</title>
            <description>Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.</description>
          </group>
          <group group_id="O2">
            <title>Midazolam</title>
            <description>Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.</description>
          </group>
        </group_list>
        <measure>
          <title>The Patient-Rated Inventory of Side Effects (PRISE)</title>
          <description>The PRISE will be used to document other general adverse events by patients before, during and after infusions. This is a patient self-report used to qualify side effects by identifying and evaluating the tolerability of each symptom. It is a 9 item assessment of the side effects in the following symptom domains; Gastrointestinal, Heart, Skin, Nervous System, Eyes/Ears, Genital/Urinary, Sleep, Sexual Functioning, and Other. Each domain has multiple symptoms which can be endorsed. For each domain the patient rates whether or not the symptoms are tolerable or distressing. Data below represent the number of participants from which there was an endorsement of each listed event.&#xD;
Participants will have the PRISE performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>dry mouth</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>diarrhoea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Constipation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea / vomiting</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Palpitation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chest pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rash</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Headache</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tremors</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Poor coordination</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dizziness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blurred vision</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Difficulty urinating</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Difficulty sleeping</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleeping too much</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Poor concentration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Restlessness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Montreal Cognitive Assessment (MoCA)</title>
        <description>The MOCA was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, conceptual thinking, calculations, and orientation. It is scored out of a maximum of 30. The higher scores indicate better cognition.&#xD;
The MOCA will be performed at baseline, one day after infusions 1 and 4 and 12 weeks after the final infusion.</description>
        <time_frame>15 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Ketamine</title>
            <description>Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.</description>
          </group>
          <group group_id="O2">
            <title>Midazolam</title>
            <description>Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.</description>
          </group>
        </group_list>
        <measure>
          <title>The Montreal Cognitive Assessment (MoCA)</title>
          <description>The MOCA was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, conceptual thinking, calculations, and orientation. It is scored out of a maximum of 30. The higher scores indicate better cognition.&#xD;
The MOCA will be performed at baseline, one day after infusions 1 and 4 and 12 weeks after the final infusion.</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="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.4" spread="3.1"/>
                    <measurement group_id="O2" value="28.5" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event information was collected over the entire study time frame, 10 months (September 2017 - June 2018). For each participant, data was collected over a period of 15 weeks which included 3 weeks of intervention and 12 weeks of follow up assessments.</time_frame>
      <desc>Tolerability of the trial agents was assessed at multiple points before, during and after treatment sessions using various assessments including the CADSS, BPRS, PRISE and YMRS. These have been used in other clinical trials which have used ketamine as a treatment for depressive disorders. We also carried out physical health assessments during the infusion clinics (e.g. vital signs).</desc>
      <group_list>
        <group group_id="E1">
          <title>Ketamine</title>
          <description>Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.</description>
        </group>
        <group group_id="E2">
          <title>Midazolam</title>
          <description>Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.&#xD;
Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.</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="13"/>
                <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="13"/>
                <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>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>
    <limitations_and_caveats>As this is a pilot trial, participant numbers are low.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr Bronagh Gallagher</name_or_title>
      <organization>Trinity College Dublin</organization>
      <phone>01 249 ext 3200</phone>
      <email>bgallag@tcd.ie</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/NCT03256162
org study id: 01/17
secondary id: 2016-004764-18
nct id: NCT03256162
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Randomised, controlled, parallel-group, pilot clinical trial of ketamine vs. midazolam as an
      adjunctive therapy for depression. The main purpose of the pilot study is to assess trial
      processes to help inform a future definitive trial.
Pragmatic, randomised, controlled, parallel-group, pilot trial. Trial participants will be
      patients admitted to St Patrick's University Hospital for treatment of a depressive episode.
      The investigators aim to recruit up to 20 participants who will be eligible for this study
      and randomly allocate 10 patients to each group. The participants will undergo usual
      inpatient care as prescribed by their treating team for the index acute depressive episode.
      Both participants and assessors will be blind to treatment allocation. Consented participants
      will be randomly allocated in a 1:1 ratio to a four week course of either once-weekly
      ketamine or midazolam infusions. Block randomisation will be independently performed.
      Physical, psychotomimetic and cognitive outcomes will be monitored before, during and after
      infusions. Blood samples will be taken at four time-points in the first infusion session and
      before the final infusion for neuroplasticity biomarker studies. Both groups will continue
      treatment as usual. Participates will also be followed up over a three month period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The Hamilton Rating Scale for Depression-24 Item Version (HRSD-24)
time frame: 15 weeks
description: The HRSD assesses severity of depressive symptoms and is commonly used to measure depression severity. It was initially a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HRSD includes items on helplessness, hopelessness and worthlessness; its score range is 0-77, with higher scores reflecting greater burden of depressive symptoms.
Response to antidepressant treatment is defined as achieving ≥60% decrease from baseline HRSD-24 and score ≤16. Remission criteria are ≥60% decrease in HRSD from baseline and score ≤10. Criteria for relapse are ≥10 point increase in HRSD-24 compared to responder baseline score plus HRSD ≥16; in addition, increase in the HRSD should be maintained one week later.
Participants will have a baseline (T0) HRSD-24 score. This will be repeated 1 week after each of 4 once-weekly infusions (T1-4) and follow-up measures after another 5 (T9) and 11 (T15) weeks, week 15 is reported.
measure: The Quick Inventory of Depressive Symptoms, Self-report Version (QIDS-SR16)
time frame: 15 weeks
description: The QIDS-SR16 is a validated self-report measure of depressive symptoms. This consists of 16 questions rated 0-3. Its score range is 0-48, with higher scores reflecting greater burden of depressive symptoms.
Participants will have a baseline (T0) QIDS-SR16 score. This will be repeated one week after each of four once-weekly infusions (T1-4) and follow-up measures after another five (T9) and 11 (T15) weeks. Week 15 scores are reported.
measure: The Clinician-Administered Dissociative States Scale (CADSS)
time frame: 4 weeks
description: The CADSS measures dissociative symptoms. It will be administered before, during and after infusions in order to capture the range of possible subjective side effects of either agent. This consists of 23 questions and scores for each question range from 0-4. The maximum score is 92 with higher scores indicating more dissociative symptoms.
Participants will have the CADSS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.
measure: The Brief Psychiatric Rating Scale (BPRS)
time frame: 4 weeks
description: The BPRS measures psychotomimetic effects. The investigators will use the positive symptoms subscale of the Brief Psychiatric Rating Scale. The 4-item positive symptoms subscale measures suspiciousness, hallucinations, unusual thought content, and conceptual disorganisation. Each question is scored between 0-7. The maximum score in this 4-item questionnaire is 28. Higher scores indicate more severe psychotic symptoms.
Participants will have the BPRS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.
measure: Young Mania Rating Scale (YMRS; Mood Item)
time frame: 4 weeks
description: Investigators will use the mood item of them YMRS to assess for psychotomimetic effects. This item is rated 0-4. The higher scores reflect elevated mood.
Participants will have the YMRS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.
measure: The Patient-Rated Inventory of Side Effects (PRISE)
time frame: 4 weeks
description: The PRISE will be used to document other general adverse events by patients before, during and after infusions. This is a patient self-report used to qualify side effects by identifying and evaluating the tolerability of each symptom. It is a 9 item assessment of the side effects in the following symptom domains; Gastrointestinal, Heart, Skin, Nervous System, Eyes/Ears, Genital/Urinary, Sleep, Sexual Functioning, and Other. Each domain has multiple symptoms which can be endorsed. For each domain the patient rates whether or not the symptoms are tolerable or distressing. Data below represent the number of participants from which there was an endorsement of each listed event.
Participants will have the PRISE performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.
measure: The Montreal Cognitive Assessment (MoCA)
time frame: 15 weeks
description: The MOCA was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, conceptual thinking, calculations, and orientation. It is scored out of a maximum of 30. The higher scores indicate better cognition.
The MOCA will be performed at baseline, one day after infusions 1 and 4 and 12 weeks after the final infusion.
arm group label: Ketamine
arm group type: Experimental
description: Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.
arm group label: Midazolam
arm group type: Active Comparator
description: Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.
intervention type: Drug
intervention name: Ketamine
description: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.
arm group label: Ketamine
other name: Ketalar
intervention type: Drug
intervention name: Midazolam
description: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.
arm group label: Midazolam
other name: Hypnovel
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Declan M McLoughlin, PhD
role: Principal Investigator
affiliation: St Patrick's Mental Health Services and Trinity College Dublin
facility: 
country: Ireland
url: https://www.tcd.ie/medicine/psychiatry/research/depression/
description: Research Team Website
responsible party type: Principal Investigator
investigator affiliation: St Patrick's Hospital, Ireland
investigator full name: Prof Declan McLoughlin
investigator title: Professor
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Bipolar Disorder
mesh term: Midazolam
mesh term: Ketamine
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: As this is a pilot trial, participant numbers are low.
point of contact: 