<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/NCT03027362</url>
  </required_header>
  <id_info>
    <org_study_id>1609018450</org_study_id>
    <nct_id>NCT03027362</nct_id>
  </id_info>
  <brief_title>Cognitive Therapy to Sustain the Antidepressant Effects of Intravenous Ketamine in Treatment-resistant Depression</brief_title>
  <official_title>Cognitive Therapy to Sustain the Antidepressant Effects of Intravenous Ketamine in Treatment-resistant Depression: a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yale University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goals of this study are: 1) to investigate the efficacy of combining ketamine with&#xD;
      intensive cognitive behavioral therapy (CBT) to sustain the antidepressant effects of&#xD;
      ketamine; and 2) to determine ketamine's delayed effects on learning and memory, and to&#xD;
      explore the relationship between any ketamine-induced changes in learning and memory and&#xD;
      duration of antidepressant efficacy, with and without CBT augmentation. Subjects with a&#xD;
      diagnosis of MDD who are treatment-resistant to at least 2 antidepressants and have chosen to&#xD;
      pursue clinical ketamine treatment at Yale Psychiatric Hospital will be recruited for the&#xD;
      study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">January 15, 2020</completion_date>
  <primary_completion_date type="Actual">September 30, 2019</primary_completion_date>
  <phase>N/A</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to relapse of depression measured by the Montgomery-Asberg Depressive Rating Scale (MADRS) score.</measure>
    <time_frame>Enrollment to 17 week follow-up</time_frame>
    <description>Relapse is defined as less than 50% improvement in MADRS compared to baseline MADRS score. The median time to relapse is the time at which the 50th percentile of participants relapses.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in cognitive flexibility-working memory</measure>
    <time_frame>Before the first ketamine treatment and 24 hours following the last ketamine treatment.</time_frame>
    <description>Measured by n-back task</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cognitive flexibility-executive function</measure>
    <time_frame>Before the first ketamine treatment and 24 hours following the last ketamine treatment.</time_frame>
    <description>Measured by set shifting task (COGSTATE test)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Depressive Disorder, Major</condition>
  <arm_group>
    <arm_group_label>Cognitive behavioral therapy (CBT) and medication</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Following clinical ketamine treatment, the intervention includes sixteen CBT sessions over 14 weeks. In addition, standard of care medications for treatment of depression, will be prescribed by the principal investigator or by a psychiatrist unaffiliated with the trial. Participants will remain on the medication they were prescribed when they entered the study and will be expected not to adjust the medication unless clinically urgent.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Psychoeducation and medication</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Following clinical ketamine treatment, the intervention includes psychoeducational sessions over 14 weeks.In addition, standard of care medications for treatment of depression, will be prescribed by the principal investigator or a by psychiatrist unaffiliated with the trial.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cognitive behavioral therapy (CBT) and medication</intervention_name>
    <description>Sixteen sessions over 14 weeks.</description>
    <arm_group_label>Cognitive behavioral therapy (CBT) and medication</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Psychoeducation and medication</intervention_name>
    <arm_group_label>Psychoeducation and medication</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Suffering from a major depressive episode based on Diagnostic and Statistical manual&#xD;
             (DSM) 5 criteria and having failed one or more standard antidepressant treatments&#xD;
             during the current episode&#xD;
&#xD;
          -  Hamilton Depression Rating Scale (17-HAM-D) score of 21 or more prior to ketamine&#xD;
             treatment.&#xD;
&#xD;
          -  Planned clinical treatment with ketamine at Yale Psychiatric Hospital (YPH)&#xD;
&#xD;
          -  As the purpose of this study is to determine the feasibility and efficacy of CBT to&#xD;
             sustain the antidepressant effects of ketamine, only those who achieve a clinical&#xD;
             response (i.e., 50% reduction in depression symptoms, as measured by the&#xD;
             Montgomery-Asberg Depressive Rating Scale (MADRS) will be eligible for randomization.&#xD;
&#xD;
          -  Patients must be treatment resistant to at least two drugs used to treat depression.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any Axis I or Axis II Disorder, which at screening is clinically predominant to their&#xD;
             depressive episode or has been predominant to their depressive episode at any time&#xD;
             within 6 months prior to screening&#xD;
&#xD;
          -  Active suicidal thoughts with a plan&#xD;
&#xD;
          -  Current or recent (&lt;6 months ago) substance use disorder&#xD;
&#xD;
          -  Non-affective psychosis (such as schizophrenia or schizoaffective disorder)&#xD;
&#xD;
          -  Inability to speak English fluently&#xD;
&#xD;
          -  A clinically significant abnormality on the screening physical examination that might&#xD;
             affect safety, study participation, or confound interpretation of study results&#xD;
&#xD;
          -  Dementia, delirium, or any other neurological or mental disease that might affect&#xD;
             cognition or the ability to meaningfully participate in cognitive behavioral therapy&#xD;
             (CBT).&#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>Samuel Wilkinson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>January 19, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <last_update_submitted>January 30, 2020</last_update_submitted>
  <last_update_submitted_qc>January 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Treatment-Resistant</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_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/NCT03027362
org study id: 1609018450
nct id: NCT03027362
lead sponsor: 
has dmc: No
The goals of this study are: 1) to investigate the efficacy of combining ketamine with
      intensive cognitive behavioral therapy (CBT) to sustain the antidepressant effects of
      ketamine; and 2) to determine ketamine's delayed effects on learning and memory, and to
      explore the relationship between any ketamine-induced changes in learning and memory and
      duration of antidepressant efficacy, with and without CBT augmentation. Subjects with a
      diagnosis of MDD who are treatment-resistant to at least 2 antidepressants and have chosen to
      pursue clinical ketamine treatment at Yale Psychiatric Hospital will be recruited for the
      study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Time to relapse of depression measured by the Montgomery-Asberg Depressive Rating Scale (MADRS) score.
time frame: Enrollment to 17 week follow-up
description: Relapse is defined as less than 50% improvement in MADRS compared to baseline MADRS score. The median time to relapse is the time at which the 50th percentile of participants relapses.
measure: Change in cognitive flexibility-working memory
time frame: Before the first ketamine treatment and 24 hours following the last ketamine treatment.
description: Measured by n-back task
measure: Change in cognitive flexibility-executive function
time frame: Before the first ketamine treatment and 24 hours following the last ketamine treatment.
description: Measured by set shifting task (COGSTATE test)
arm group label: Cognitive behavioral therapy (CBT) and medication
arm group type: Experimental
description: Following clinical ketamine treatment, the intervention includes sixteen CBT sessions over 14 weeks. In addition, standard of care medications for treatment of depression, will be prescribed by the principal investigator or by a psychiatrist unaffiliated with the trial. Participants will remain on the medication they were prescribed when they entered the study and will be expected not to adjust the medication unless clinically urgent.
arm group label: Psychoeducation and medication
arm group type: Active Comparator
description: Following clinical ketamine treatment, the intervention includes psychoeducational sessions over 14 weeks.In addition, standard of care medications for treatment of depression, will be prescribed by the principal investigator or a by psychiatrist unaffiliated with the trial.
intervention type: Other
intervention name: Cognitive behavioral therapy (CBT) and medication
description: Sixteen sessions over 14 weeks.
arm group label: Cognitive behavioral therapy (CBT) and medication
intervention type: Other
intervention name: Psychoeducation and medication
arm group label: Psychoeducation and medication
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Samuel Wilkinson, MD
role: Principal Investigator
affiliation: Yale University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Treatment-Resistant
mesh term: Depressive Disorder, Major