<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/NCT03039842</url>
  </required_header>
  <id_info>
    <org_study_id>CombindBP2014</org_study_id>
    <nct_id>NCT03039842</nct_id>
  </id_info>
  <brief_title>Combination of Dextromethorphan and Memantine in Treating Bipolar Disorder</brief_title>
  <official_title>Combination of Dextromethorphan and Memantine in Treating Bipolar Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cheng-Kung University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cheng-Kung University Hospital</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a research clinical trial of double-blind, stratified randomized, parallel group,&#xD;
      two-centre study. It will be conducted in a total of 250~300 male and female subjects from&#xD;
      the Department of Psychiatry at National Cheng Kung University Hospital. Eligible subjects&#xD;
      will be psychiatric out- and in-patients, aged between 18~65 years old, who have psychiatric&#xD;
      evaluation with clinically suspected of having bipolar II disorder and fulfill the inclusion&#xD;
      and exclusion criteria. The add-on double-blind study treatment with dextromethorphan/place&#xD;
      will commence at randomization for while patients continue open-label valproate. Subjects&#xD;
      will be enrolled for 12 weeks double-blind add-on treatment and randomly assigned to (1) 30mg&#xD;
      dextromethorphan+valproate, (2) 5mg memantine+valproate, (3)&#xD;
      dextromethorphan+memantine+valproate or (4) placebo+valproate. Concomitant benzodiazepine&#xD;
      medication (preferably up to 8mg lorazepam) may be used for daytime sedation, agitation or&#xD;
      insomnia during the study. For the consideration of the less influence to immune-system,&#xD;
      resperidone 1-3mg/daily and fluoxetine maximum 20mg/daily will be chose. We will measure the&#xD;
      treatment response and side effect to clarify the curative effect of DM and memantine add-on&#xD;
      therapy to valproate in the treatment of bipolar disorders. This study is being performed to&#xD;
      investigate the possibly significant beneficial effects on the subtypes of bipolar disorders&#xD;
      psychopathology.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A total of 250~300 male and female subjects from the Department of Psychiatry at National&#xD;
      Cheng Kung University Hospital. Eligible subjects who are aged between 18~65 years old and&#xD;
      clinically suspected of having bipolar II disorder are invited. The add-on double-blind study&#xD;
      treatment with dextromethorphan/place will commence at randomization for while patients&#xD;
      continue open-label valproate. Subjects will be enrolled for 12 weeks double-blind add-on&#xD;
      treatment and randomly assigned to (1) 30mg dextromethorphan+valproate, (2) 5mg&#xD;
      memantine+valproate, (3) dextromethorphan+memantine+valproate or (4) placebo+valproate.&#xD;
      Concomitant benzodiazepine medication (preferably up to 8mg lorazepam) may be used for&#xD;
      daytime sedation, agitation or insomnia during the study. For the consideration of the less&#xD;
      influence to immune-system, resperidone 1-3mg/daily and fluoxetine maximum 20mg/daily will be&#xD;
      chose. We will measure the treatment response and side effect to clarify the curative effect&#xD;
      of DM and memantine add-on therapy to valproate in the treatment of bipolar disorders. This&#xD;
      study is being performed to investigate the possibly significant beneficial effects on the&#xD;
      subtypes of bipolar disorders psychopathology.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date type="Actual">January 1, 2013</start_date>
  <completion_date type="Anticipated">December 31, 2017</completion_date>
  <primary_completion_date type="Actual">December 31, 2016</primary_completion_date>
  <phase>Phase 3</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>treatment change assessed by plasma levels of cytokines (e.g., IL-6, IL-8)</measure>
    <time_frame>baseline, week 1, week 2, week 4, week 8, week 12</time_frame>
    <description>change assessment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>depression change change</measure>
    <time_frame>baseline, week 1, week 2, week 4, week 8, week 12</time_frame>
    <description>depression change assessed by Hamilton Depression Rating Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>manic state change</measure>
    <time_frame>baseline, week 1, week 2, week 4, week 8, week 12</time_frame>
    <description>Manic symptom assessed by Young Mania Rating Scale</description>
  </secondary_outcome>
  <other_outcome>
    <measure>attention function change</measure>
    <time_frame>baseline, week 12</time_frame>
    <description>attention change assessed by CPT</description>
  </other_outcome>
  <other_outcome>
    <measure>memory change</measure>
    <time_frame>baseline, week 12</time_frame>
    <description>memory change assessed by WMS</description>
  </other_outcome>
  <other_outcome>
    <measure>executive functioning change</measure>
    <time_frame>baseline, week 12</time_frame>
    <description>executive function change assessed by WCST</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Bipolar Disorder II</condition>
  <arm_group>
    <arm_group_label>30 mg DM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30mg dextromethorphan+valproate</description>
  </arm_group>
  <arm_group>
    <arm_group_label>5 mg MM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>5mg memantine+valproate</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DM+MM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>dextromethorphan+memantine+ valproate</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo+valproate</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dextromethorphan</intervention_name>
    <arm_group_label>30 mg DM</arm_group_label>
    <other_name>30mg dextromethorphan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Memantine</intervention_name>
    <arm_group_label>5 mg MM</arm_group_label>
    <other_name>5mg memantine+valproate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>dextromethorphan+memantine</intervention_name>
    <arm_group_label>DM+MM</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo+valproate</intervention_name>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A 2-day minimum for hypomania to diagnose bipolar II disorder&#xD;
&#xD;
          -  A total of Hamilton Rating Scale for Depression scored at least 18 or Young Mania&#xD;
             Rating Scale scored at least 14 at the screening stage&#xD;
&#xD;
          -  Must allow to ensure acceptable compliance and visit&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant females or nursing&#xD;
&#xD;
          -  Women of childbearing potential not using adequate contraception&#xD;
&#xD;
          -  Received dextromethorphan, memantine, other antiinflammatory medication within 1 week&#xD;
             prior&#xD;
&#xD;
          -  Clinically significant medical condition (cardiac, hepatic and renal disease)&#xD;
&#xD;
          -  Received electroconvulsive therapy patients within 4 weeks prior to the first dose of&#xD;
             double-blind medication&#xD;
&#xD;
          -  Increase in total SGOT, SGPT, BUN and creatinine by more than 3X upper limit of&#xD;
             normal.&#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>Ru-Band Lu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Psychiatry, National Cheng Kung University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Cheng Kung University Hospital</name>
      <address>
        <city>Tainan</city>
        <zip>704</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>August 29, 2014</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 1, 2017</study_first_posted>
  <last_update_submitted>July 6, 2017</last_update_submitted>
  <last_update_submitted_qc>July 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Cheng-Kung University Hospital</investigator_affiliation>
    <investigator_full_name>Ru-Band Lu</investigator_full_name>
    <investigator_title>Distinguished Professor</investigator_title>
  </responsible_party>
  <keyword>dextromethorphan; memantine; treatment response</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bipolar Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Valproic Acid</mesh_term>
    <mesh_term>Memantine</mesh_term>
    <mesh_term>Dextromethorphan</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/NCT03039842
org study id: CombindBP2014
nct id: NCT03039842
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a research clinical trial of double-blind, stratified randomized, parallel group,
      two-centre study. It will be conducted in a total of 250~300 male and female subjects from
      the Department of Psychiatry at National Cheng Kung University Hospital. Eligible subjects
      will be psychiatric out- and in-patients, aged between 18~65 years old, who have psychiatric
      evaluation with clinically suspected of having bipolar II disorder and fulfill the inclusion
      and exclusion criteria. The add-on double-blind study treatment with dextromethorphan/place
      will commence at randomization for while patients continue open-label valproate. Subjects
      will be enrolled for 12 weeks double-blind add-on treatment and randomly assigned to (1) 30mg
      dextromethorphan+valproate, (2) 5mg memantine+valproate, (3)
      dextromethorphan+memantine+valproate or (4) placebo+valproate. Concomitant benzodiazepine
      medication (preferably up to 8mg lorazepam) may be used for daytime sedation, agitation or
      insomnia during the study. For the consideration of the less influence to immune-system,
      resperidone 1-3mg/daily and fluoxetine maximum 20mg/daily will be chose. We will measure the
      treatment response and side effect to clarify the curative effect of DM and memantine add-on
      therapy to valproate in the treatment of bipolar disorders. This study is being performed to
      investigate the possibly significant beneficial effects on the subtypes of bipolar disorders
      psychopathology.
A total of 250~300 male and female subjects from the Department of Psychiatry at National
      Cheng Kung University Hospital. Eligible subjects who are aged between 18~65 years old and
      clinically suspected of having bipolar II disorder are invited. The add-on double-blind study
      treatment with dextromethorphan/place will commence at randomization for while patients
      continue open-label valproate. Subjects will be enrolled for 12 weeks double-blind add-on
      treatment and randomly assigned to (1) 30mg dextromethorphan+valproate, (2) 5mg
      memantine+valproate, (3) dextromethorphan+memantine+valproate or (4) placebo+valproate.
      Concomitant benzodiazepine medication (preferably up to 8mg lorazepam) may be used for
      daytime sedation, agitation or insomnia during the study. For the consideration of the less
      influence to immune-system, resperidone 1-3mg/daily and fluoxetine maximum 20mg/daily will be
      chose. We will measure the treatment response and side effect to clarify the curative effect
      of DM and memantine add-on therapy to valproate in the treatment of bipolar disorders. This
      study is being performed to investigate the possibly significant beneficial effects on the
      subtypes of bipolar disorders psychopathology.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: treatment change assessed by plasma levels of cytokines (e.g., IL-6, IL-8)
time frame: baseline, week 1, week 2, week 4, week 8, week 12
description: change assessment
measure: depression change change
time frame: baseline, week 1, week 2, week 4, week 8, week 12
description: depression change assessed by Hamilton Depression Rating Scale
measure: manic state change
time frame: baseline, week 1, week 2, week 4, week 8, week 12
description: Manic symptom assessed by Young Mania Rating Scale
measure: attention function change
time frame: baseline, week 12
description: attention change assessed by CPT
measure: memory change
time frame: baseline, week 12
description: memory change assessed by WMS
measure: executive functioning change
time frame: baseline, week 12
description: executive function change assessed by WCST
arm group label: 30 mg DM
arm group type: Experimental
description: 30mg dextromethorphan+valproate
arm group label: 5 mg MM
arm group type: Experimental
description: 5mg memantine+valproate
arm group label: DM+MM
arm group type: Experimental
description: dextromethorphan+memantine+ valproate
arm group label: placebo
arm group type: Placebo Comparator
description: Placebo+valproate
intervention type: Drug
intervention name: Dextromethorphan
arm group label: 30 mg DM
other name: 30mg dextromethorphan
intervention type: Drug
intervention name: Memantine
arm group label: 5 mg MM
other name: 5mg memantine+valproate
intervention type: Drug
intervention name: dextromethorphan+memantine
arm group label: DM+MM
intervention type: Drug
intervention name: placebo+valproate
arm group label: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Ru-Band Lu, MD
role: Principal Investigator
affiliation: Department of Psychiatry, National Cheng Kung University
facility: 
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: National Cheng-Kung University Hospital
investigator full name: Ru-Band Lu
investigator title: Distinguished Professor
mesh term: Bipolar Disorder
mesh term: Valproic Acid
mesh term: Memantine
mesh term: Dextromethorphan
sharing ipd: No