<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/NCT02219867</url>
  </required_header>
  <id_info>
    <org_study_id>Sheba- Ketamine</org_study_id>
    <nct_id>NCT02219867</nct_id>
  </id_info>
  <brief_title>Ketamine Infusions for Major Depression Disorder</brief_title>
  <acronym>Ketamie</acronym>
  <official_title>Evaluation of Safety and Efficacy of Sub-anesthetic Ketamine Infusions as a Treatment for Patients Diagnosed With Resistant Major Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sheba Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Tel Aviv University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sheba Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Ketamine has been safely used for induction and maintenance of anesthesia for decades and&#xD;
      more recently has been used for chronic pain. Ketamine is a noncompetitive, high-affinity&#xD;
      antagonist of the N-methyl-D-aspartate type glutamate receptor, with additional effects on&#xD;
      dopamine and μ-opioid receptors. During the last 9 years several uncontrolled reports have&#xD;
      been published, showing a rapid and impressive effect of ketamine in TRD patients (Berman,&#xD;
      Cappiello et al. 2000; Zarate, Singh et al. 2006; Mathew, Murrough et al. 2010; Aan Het Rot,&#xD;
      Zarate et al. 2012; Mathew, Shah et al. 2012; Murrough, Iosifescu et al. 2013). Recently&#xD;
      three placebo-controlled trials showed that a single dose of sub-anesthetic, (0.5 mg/kg) slow&#xD;
      intravenous (IV) ketamine improves depressive symptoms dramatically. Across studies, a&#xD;
      clinically significant antidepressant response was maintained for up to 72 hours in 12 of 25&#xD;
      patients. Nonetheless, all but two patients relapsed &lt;2 weeks post-ketamine (Zarate, Singh et&#xD;
      al. 2006; aan Het Rot, Zarate et al. 2012). Rot et al. showed that repeated IV ketamine&#xD;
      infusions prolongs the duration of improvement.&#xD;
&#xD;
      The investigators believe that the data presented above allows us to provide ketamine&#xD;
      treatment here in the Sheba Medical Center for TRD patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Major depressive disorder (MDD) is one of the leading causes of disability worldwide&#xD;
      (Collins, Patel et al. 2011). A substantial proportion of patients do not achieve adequate&#xD;
      remission despite multiple antidepressant trials and augmentation strategies (Rush, Trivedi&#xD;
      et al. 2006; Weissman, Pilowsky et al. 2006). Treatment-resistant major depression (TRD) is&#xD;
      defined as an insufficient response to at least two adequate antidepressant trials (Rush,&#xD;
      Trivedi et al. 2006). Many of these patients are referred to previous somatic treatment e.g.&#xD;
      electroconvulsive therapy (ECT), rapid Transcranial Magnetic Stimulation (rTMS) and Vagal&#xD;
      Nerve Stimulation (VNS), all of which have serious disadvantages and/or limited efficacy.&#xD;
&#xD;
      Ketamine has been safely used for induction and maintenance of anesthesia for decades and&#xD;
      more recently has been used for chronic pain. Ketamine is a noncompetitive, high-affinity&#xD;
      antagonist of the N-methyl-D-aspartate type glutamate receptor, with additional effects on&#xD;
      dopamine and μ-opioid receptors. During the last 9 years several uncontrolled reports have&#xD;
      been published, showing a rapid and impressive effect of ketamine in TRD patients (Berman,&#xD;
      Cappiello et al. 2000; Zarate, Singh et al. 2006; Mathew, Murrough et al. 2010; Aan Het Rot,&#xD;
      Zarate et al. 2012; Mathew, Shah et al. 2012; Murrough, Iosifescu et al. 2013). Recently&#xD;
      three placebo-controlled trials showed that a single dose of sub-anesthetic, (0.5 mg/kg) slow&#xD;
      intravenous (IV) ketamine improves depressive symptoms dramatically. Across studies, a&#xD;
      clinically significant antidepressant response was maintained for up to 72 hours in 12 of 25&#xD;
      patients. Nonetheless, all but two patients relapsed &lt;2 weeks post-ketamine (Zarate, Singh et&#xD;
      al. 2006; aan Het Rot, Zarate et al. 2012). Rot et al. showed that repeated IV ketamine&#xD;
      infusions prolongs the duration of improvement.&#xD;
&#xD;
      The investigators believe that the data presented above allows us to provide ketamine&#xD;
      treatment here in the Sheba Medical Center for TRD patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>August 2014</start_date>
  <completion_date type="Anticipated">August 2017</completion_date>
  <primary_completion_date type="Anticipated">January 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Montgomery Asberg Rating scale - MADRS</measure>
    <time_frame>24 hours after treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Side effects monitoring</measure>
    <time_frame>Up to 4 hours after ketamine infustion</time_frame>
    <description>Blood pressure monitoring Dissociative symptoms detection and description</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Hamilston depression Rating Scale</measure>
    <time_frame>Up to 30 days from last treatment</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Depressive Disorder, Major</condition>
  <arm_group>
    <arm_group_label>Ketamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Active Comparator</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>Drug (including placebo)</description>
    <arm_group_label>Ketamine</arm_group_label>
    <other_name>ketalar</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of Major Depressive disorder, chronic and/or recurrent of at least at&#xD;
             moderate severity, determined as reflected by baseline scores of ≥32 on the Inventory&#xD;
             of Depressive Symptomatology -Clinician rated IDS-C30&#xD;
&#xD;
          -  Patients with demonstrated insufficient response to ≥2 adequate antidepressant trials&#xD;
             in the current episode&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current psychotic or dissociative symptoms&#xD;
&#xD;
          -  Severe personality disorder with psychosis or dissociative symptoms&#xD;
&#xD;
          -  Lifetime history of psychotic mania&#xD;
&#xD;
          -  Substance use disorder&#xD;
&#xD;
          -  Current suicidal ideation&#xD;
&#xD;
          -  Uncontrolled elevated blood pressure, non-sinus rhythm, unstable ischemic heart&#xD;
             disease, uncorrected hyper thyroidism, and for women, pregnancy or the initiation of&#xD;
             or female hormonal treatment &lt;3 months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sheba MC</name>
      <address>
        <city>Ramat Gan</city>
        <zip>5265601</zip>
        <country>Israel</country>
      </address>
    </facility>
    <contact>
      <last_name>Revital Amiaz, Dr</last_name>
      <phone>972-35303436</phone>
      <email>revital.amiaz@sheba.health.gov.il</email>
    </contact>
    <investigator>
      <last_name>Revital Amiaz, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 12, 2014</study_first_submitted>
  <study_first_submitted_qc>August 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 19, 2014</study_first_posted>
  <last_update_submitted>August 28, 2014</last_update_submitted>
  <last_update_submitted_qc>August 28, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 29, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sheba Medical Center</investigator_affiliation>
    <investigator_full_name>Dr. Revital Amiaz</investigator_full_name>
    <investigator_title>Doctor</investigator_title>
  </responsible_party>
  <keyword>ketamine</keyword>
  <keyword>MDD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02219867
org study id: Sheba- Ketamine
nct id: NCT02219867
lead sponsor: 
collaborator: 
has dmc: Yes
Ketamine has been safely used for induction and maintenance of anesthesia for decades and
      more recently has been used for chronic pain. Ketamine is a noncompetitive, high-affinity
      antagonist of the N-methyl-D-aspartate type glutamate receptor, with additional effects on
      dopamine and μ-opioid receptors. During the last 9 years several uncontrolled reports have
      been published, showing a rapid and impressive effect of ketamine in TRD patients (Berman,
      Cappiello et al. 2000; Zarate, Singh et al. 2006; Mathew, Murrough et al. 2010; Aan Het Rot,
      Zarate et al. 2012; Mathew, Shah et al. 2012; Murrough, Iosifescu et al. 2013). Recently
      three placebo-controlled trials showed that a single dose of sub-anesthetic, (0.5 mg/kg) slow
      intravenous (IV) ketamine improves depressive symptoms dramatically. Across studies, a
      clinically significant antidepressant response was maintained for up to 72 hours in 12 of 25
      patients. Nonetheless, all but two patients relapsed <2 weeks post-ketamine (Zarate, Singh et
      al. 2006; aan Het Rot, Zarate et al. 2012). Rot et al. showed that repeated IV ketamine
      infusions prolongs the duration of improvement.

      The investigators believe that the data presented above allows us to provide ketamine
      treatment here in the Sheba Medical Center for TRD patients.
Major depressive disorder (MDD) is one of the leading causes of disability worldwide
      (Collins, Patel et al. 2011). A substantial proportion of patients do not achieve adequate
      remission despite multiple antidepressant trials and augmentation strategies (Rush, Trivedi
      et al. 2006; Weissman, Pilowsky et al. 2006). Treatment-resistant major depression (TRD) is
      defined as an insufficient response to at least two adequate antidepressant trials (Rush,
      Trivedi et al. 2006). Many of these patients are referred to previous somatic treatment e.g.
      electroconvulsive therapy (ECT), rapid Transcranial Magnetic Stimulation (rTMS) and Vagal
      Nerve Stimulation (VNS), all of which have serious disadvantages and/or limited efficacy.

      Ketamine has been safely used for induction and maintenance of anesthesia for decades and
      more recently has been used for chronic pain. Ketamine is a noncompetitive, high-affinity
      antagonist of the N-methyl-D-aspartate type glutamate receptor, with additional effects on
      dopamine and μ-opioid receptors. During the last 9 years several uncontrolled reports have
      been published, showing a rapid and impressive effect of ketamine in TRD patients (Berman,
      Cappiello et al. 2000; Zarate, Singh et al. 2006; Mathew, Murrough et al. 2010; Aan Het Rot,
      Zarate et al. 2012; Mathew, Shah et al. 2012; Murrough, Iosifescu et al. 2013). Recently
      three placebo-controlled trials showed that a single dose of sub-anesthetic, (0.5 mg/kg) slow
      intravenous (IV) ketamine improves depressive symptoms dramatically. Across studies, a
      clinically significant antidepressant response was maintained for up to 72 hours in 12 of 25
      patients. Nonetheless, all but two patients relapsed <2 weeks post-ketamine (Zarate, Singh et
      al. 2006; aan Het Rot, Zarate et al. 2012). Rot et al. showed that repeated IV ketamine
      infusions prolongs the duration of improvement.

      The investigators believe that the data presented above allows us to provide ketamine
      treatment here in the Sheba Medical Center for TRD patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Montgomery Asberg Rating scale - MADRS
time frame: 24 hours after treatment
measure: Side effects monitoring
time frame: Up to 4 hours after ketamine infustion
description: Blood pressure monitoring Dissociative symptoms detection and description
measure: Hamilston depression Rating Scale
time frame: Up to 30 days from last treatment
arm group label: Ketamine
arm group type: Experimental
description: Active Comparator
intervention type: Drug
intervention name: Ketamine
description: Drug (including placebo)
arm group label: Ketamine
other name: ketalar
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
facility: 
contact: 
investigator: 
country: Israel
responsible party type: Principal Investigator
investigator affiliation: Sheba Medical Center
investigator full name: Dr. Revital Amiaz
investigator title: Doctor
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Ketamine