<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/NCT03290963</url>
  </required_header>
  <id_info>
    <org_study_id>17-000819</org_study_id>
    <nct_id>NCT03290963</nct_id>
  </id_info>
  <brief_title>Effect of Lithium Versus Placebo in Adults With Treatment-Resistant Depression Who Are Receiving Ketamine</brief_title>
  <official_title>Targeting mTOR/GSK3 With Lithium Augmentation to Enhance and Sustain Rapid Antidepressant Actions of Ketamine in Adults With Treatment-Resistant Depression: A Precision Medicine Approach for Psychiatry</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>William V. Bobo, M.D.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to compare the antidepressant effect of lithium versus&#xD;
      placebo in adults receiving ketamine. Lithium is available commercially for depression;&#xD;
      ketamine is available commercially and can help the symptoms of depression; however, it has&#xD;
      not been approved by the U.S. Food and Drug Administration (FDA) for this use. The FDA has&#xD;
      allowed the use of this drug in this research study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized clinical trial in adults with Treatment-Resistant Depression. All&#xD;
      participants will receive three intravenous (IV) Ketamine (KET) infusions over 7 days. Before&#xD;
      receiving the first KET infusion, subjects will be randomized to 2 weeks of pre-KET treatment&#xD;
      with either Lithium or matching placebo. Pre-treatment medications will then be continued in&#xD;
      a double-blind manner during the acute phase administration of ketamine. Questionnaires will&#xD;
      be administered at baseline, prior to each KET infusion, and at 40, 100, and 120 minutes&#xD;
      after each infusion, and again at weekly intervals following the third (final) KET infusion&#xD;
      for 4 weeks, using standardized rating scales. Those who achieve positive response (&gt;50%&#xD;
      decrease in questionnaire total score from baseline) will be given 4 additional once-weekly&#xD;
      KET infusions (same dose and infusion rate).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Principal Investigator moved to Jacksonville, FL campus.&#xD;
  </why_stopped>
  <start_date type="Actual">November 30, 2017</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Triple blinded study. The staff accessible to the blind includes pharmacy staff and one assigned investigator.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Montgomery-Asberg Depression Rating Scale (MADRS)</measure>
    <time_frame>baseline, at the end of the first infusion (approximately 1 day)</time_frame>
    <description>The Montgomery Asberg Depression Scale (MADRS) is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Montgomery-Asberg Depression Rating Scale (MADRS)</measure>
    <time_frame>baseline, at the end of third infusion (approximately 7 days)</time_frame>
    <description>The Montgomery Asberg Depression Scale (MADRS) is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed).</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Treatment Resistant Depression</condition>
  <arm_group>
    <arm_group_label>Ketamine plus Lithium</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lithium will be used in conjunction to Ketamine infusions for the treatment of major depression disorder or bipolar disorder type I or II. Before the first ketamine infusion, subjects will be randomized to 2 weeks of lithium treatment. All subjects will receive three IV ketamine infusions (0.5 mg/kg, over 100 min.) over 7 days. Those who achieve positive response (&gt;50% decrease in MADRS total score from baseline) will be given 4 additional once-weekly ketamine infusions (same dose and infusion rate) and lithium treatment .</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ketamine plus Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo tablets will be used in conjunction to Ketamine infusions for the treatment of major depression disorder or bipolar disorder type I or II. Before the first ketamine infusion, subjects will be randomized to 2 weeks of placebo treatment. All subjects will receive three IV ketamine infusions (0.5 mg/kg, over 100 min.) over 7 days. Those who achieve positive response (&gt;50% decrease in MADRS total score from baseline) will be given 4 additional once-weekly ketamine infusions (same dose and infusion rate) and placebo treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lithium</intervention_name>
    <description>Lithium will be dosed in units (LI level &gt; or = 0.4 milliequivalents (mEq)/L)</description>
    <arm_group_label>Ketamine plus Lithium</arm_group_label>
    <other_name>Lithane</other_name>
    <other_name>Lithobid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo tablets, dosed in units</description>
    <arm_group_label>Ketamine plus Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>All subjects will receive 3 IV ketamine infusions of 0.5mg/kg, over 100 min. over 7 days.</description>
    <arm_group_label>Ketamine plus Lithium</arm_group_label>
    <arm_group_label>Ketamine plus Placebo</arm_group_label>
    <other_name>Ketalar</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability to provide informed consent;&#xD;
&#xD;
          -  Current psychiatric inpatient (voluntary only) or outpatient treatment;&#xD;
&#xD;
          -  Meets Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5)&#xD;
             diagnostic criteria for major depressive disorder, bipolar I disorder, or bipolar II&#xD;
             disorder;&#xD;
&#xD;
          -  9-item Patient Health Questionnaire (PHQ-9) total score &gt; 15 at screening and at&#xD;
             baseline (just prior to first acute phase ketamine infusion);&#xD;
&#xD;
          -  Treatment-resistant depression, as defined by failure of at least two previous&#xD;
             antidepressant or mood stabilizing treatments within the current depressive episode.&#xD;
             Failed antidepressant or mood stabilizing treatments can include pharmacotherapy for&#xD;
             depression at an adequate dose for at least 8 weeks, or an acute series of at least 6&#xD;
             administrations of electroconvulsive therapy (ECT);&#xD;
&#xD;
          -  Adequate social support, defined as having at least one individual identified who is&#xD;
             committed to function as support, including providing transportation to and from&#xD;
             outpatient ketamine infusion visits;&#xD;
&#xD;
          -  Ability to pass a comprehension assessment test related to effects of ketamine and&#xD;
             trial objectives and criteria.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of schizophrenia, schizoaffective disorder, or active psychotic symptoms;&#xD;
&#xD;
          -  On active lithium treatment;&#xD;
&#xD;
          -  Serious risk for suicide, as assessed by the evaluating study clinician; a serious&#xD;
             suicide risk will be considered: (a) an inability to control suicide impulses or&#xD;
             imminent or unacceptably high risk of suicide in the investigator's judgment; or (b) a&#xD;
             recent history of suicidal behavior, which is defined as either one or more suicide&#xD;
             attempts (or interrupted suicide attempts) in the 12 months before study entry; or (c)&#xD;
             history of serious suicidal behavior, defined as one or more suicide attempts (or&#xD;
             interrupted attempts) in the last 3 years with a potential lethality judged by the&#xD;
             evaluating study clinician to have possibly resulted in serious injury or death;&#xD;
&#xD;
          -  Ongoing prescription of &gt; 4 mg lorazepam equivalents (total) daily, or morning dosing&#xD;
             of any benzodiazepine at the time of assessment;&#xD;
&#xD;
          -  Currently undergoing ECT, transcranial magnetic stimulation, vagal nerve stimulation,&#xD;
             or deep brain stimulation as either an acute or maintenance treatment of depression;&#xD;
&#xD;
          -  Any active or unstable medical condition judged by the study psychiatrist as&#xD;
             conferring too great a level of medical risk to allow inclusion in the study;&#xD;
&#xD;
          -  Use or abuse of methamphetamine, cocaine, cannabis, or stimulants (prescribed and&#xD;
             illicit) within the past 12 months;&#xD;
&#xD;
          -  Any current abuse or dependence of alcohol or drugs (excluding nicotine and caffeine).&#xD;
             Note: Persons will be allowed to enroll in this study if their drug or alcohol&#xD;
             abuse/dependence is in complete (not partial) and sustained (&gt; 1 year) remission;&#xD;
&#xD;
          -  History of traumatic brain injury that resulted in loss of consciousness;&#xD;
&#xD;
          -  Developmental delay, mental retardation, or intellectual disorder;&#xD;
&#xD;
          -  Clinical or self-reported diagnosis of delirium, encephalopathy, or related clinical&#xD;
             diagnosis within the prior 12 months;&#xD;
&#xD;
          -  Cognitive disorder (mild and major categories, per DSM-5);&#xD;
&#xD;
          -  Prior participation in another study of ketamine for depression within the prior 6&#xD;
             months;&#xD;
&#xD;
          -  History of either poor antidepressive response to or poor tolerability of ketamine&#xD;
             (any route of administration) when previously administered for treating symptoms of&#xD;
             depression;&#xD;
&#xD;
          -  History of hypothyroidism unless taking a stable dose of thyroid medication and&#xD;
             asymptomatic for 6 months;&#xD;
&#xD;
          -  Significant unstable medical condition&#xD;
&#xD;
          -  Hepatic insufficiency (2.5 X Upper Limit of Normal (ULN) for Aspartate&#xD;
             Aminotransferase (AST) or Alanine Aminotransferase (ALT)) within 1 year of consent,&#xD;
             past liver transplant recipient, and/or clinical diagnosis of cirrhosis of the liver;&#xD;
&#xD;
          -  History of either poor antidepressive response to or poor tolerability of ketamine&#xD;
             (any route of administration) when previously administered for treating symptoms of&#xD;
             depression;&#xD;
&#xD;
          -  History of medical condition(s) which are not recommended to be taken concurrently&#xD;
             with lithium; Current anti-depressive pharmacotherapies will not be allowed during the&#xD;
             acute phase KET infusions.&#xD;
&#xD;
          -  Pregnancy, or nursing;&#xD;
&#xD;
          -  Prisoners;&#xD;
&#xD;
          -  Involuntary psychiatric hospitalization.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>William V Bobo</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>September 20, 2017</study_first_submitted>
  <study_first_submitted_qc>September 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>August 14, 2018</last_update_submitted>
  <last_update_submitted_qc>August 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 16, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>William V. Bobo, M.D.</investigator_full_name>
    <investigator_title>Professor of Psychiatry</investigator_title>
  </responsible_party>
  <keyword>depression</keyword>
  <keyword>bipolar I disorder</keyword>
  <keyword>bipolar II disorder</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Treatment-Resistant</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03290963
org study id: 17-000819
nct id: NCT03290963
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this research study is to compare the antidepressant effect of lithium versus
      placebo in adults receiving ketamine. Lithium is available commercially for depression;
      ketamine is available commercially and can help the symptoms of depression; however, it has
      not been approved by the U.S. Food and Drug Administration (FDA) for this use. The FDA has
      allowed the use of this drug in this research study.
This is a randomized clinical trial in adults with Treatment-Resistant Depression. All
      participants will receive three intravenous (IV) Ketamine (KET) infusions over 7 days. Before
      receiving the first KET infusion, subjects will be randomized to 2 weeks of pre-KET treatment
      with either Lithium or matching placebo. Pre-treatment medications will then be continued in
      a double-blind manner during the acute phase administration of ketamine. Questionnaires will
      be administered at baseline, prior to each KET infusion, and at 40, 100, and 120 minutes
      after each infusion, and again at weekly intervals following the third (final) KET infusion
      for 4 weeks, using standardized rating scales. Those who achieve positive response (>50%
      decrease in questionnaire total score from baseline) will be given 4 additional once-weekly
      KET infusions (same dose and infusion rate).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Triple blinded study. The staff accessible to the blind includes pharmacy staff and one assigned investigator.
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS)
time frame: baseline, at the end of the first infusion (approximately 1 day)
description: The Montgomery Asberg Depression Scale (MADRS) is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed).
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS)
time frame: baseline, at the end of third infusion (approximately 7 days)
description: The Montgomery Asberg Depression Scale (MADRS) is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed).
arm group label: Ketamine plus Lithium
arm group type: Active Comparator
description: Lithium will be used in conjunction to Ketamine infusions for the treatment of major depression disorder or bipolar disorder type I or II. Before the first ketamine infusion, subjects will be randomized to 2 weeks of lithium treatment. All subjects will receive three IV ketamine infusions (0.5 mg/kg, over 100 min.) over 7 days. Those who achieve positive response (>50% decrease in MADRS total score from baseline) will be given 4 additional once-weekly ketamine infusions (same dose and infusion rate) and lithium treatment .
arm group label: Ketamine plus Placebo
arm group type: Placebo Comparator
description: Placebo tablets will be used in conjunction to Ketamine infusions for the treatment of major depression disorder or bipolar disorder type I or II. Before the first ketamine infusion, subjects will be randomized to 2 weeks of placebo treatment. All subjects will receive three IV ketamine infusions (0.5 mg/kg, over 100 min.) over 7 days. Those who achieve positive response (>50% decrease in MADRS total score from baseline) will be given 4 additional once-weekly ketamine infusions (same dose and infusion rate) and placebo treatment.
intervention type: Drug
intervention name: Lithium
description: Lithium will be dosed in units (LI level > or = 0.4 milliequivalents (mEq)/L)
arm group label: Ketamine plus Lithium
other name: Lithane
other name: Lithobid
intervention type: Drug
intervention name: Placebo
description: Placebo tablets, dosed in units
arm group label: Ketamine plus Placebo
intervention type: Drug
intervention name: Ketamine
description: All subjects will receive 3 IV ketamine infusions of 0.5mg/kg, over 100 min. over 7 days.
arm group label: Ketamine plus Lithium
arm group label: Ketamine plus Placebo
other name: Ketalar
criteria: 
gender: All
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: No
last name: William V Bobo
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Mayo Clinic
investigator full name: William V. Bobo, M.D.
investigator title: Professor of Psychiatry
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Treatment-Resistant
mesh term: Ketamine
sharing ipd: No