xml: <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/NCT05977023</url>
    </required_header>
    <id_info>
      <org_study_id>CMUH111-REC2-222</org_study_id>
      <nct_id>NCT05977023</nct_id>
    </id_info>
    <brief_title>NMDA Receptor Modulation for the Treatment of Bipolar I Disorder</brief_title>
    <official_title>NMDA Receptor Modulation for the Treatment of Cognitive Impairment and Perceived Stress in Bipolar I Disorder</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>China Medical University Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Science and Technology Council</agency>
        <agency_class>U.S. Fed</agency_class>
      </collaborator>
    </sponsors>
    <source>China Medical 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>
    </oversight_info>
    <brief_summary>
      <textblock>
        At present, the treatment of Bipolar I disorder (BD-I), especially its depressive episode&#xD;
        (bipolar depression), is still limited, because there is no effective treatment for the&#xD;
        associated cognitive impairment and perceived stress. NMDA receptor (NMDAR) dysfunction is&#xD;
        associated with BD-I, particularly its cognitive impairment and perceived stress. This study&#xD;
        aims to examine the efficacy and safety of an NMDA enhancer (NMDAE) in the treatment of&#xD;
        cognitive impairment and perceived stress in the patients with bipolar depression.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Bipolar I disorder (BD-I) is a severe brain disorder. At present, the treatment of BD-I,&#xD;
        especially its depressive episode (bipolar depression), is still limited, because there is no&#xD;
        effective treatment for the associated cognitive impairment and perceived stress. This study&#xD;
        aims to examine the efficacy and safety of an NMDA enhancer (NMDAE) in the treatment of&#xD;
        cognitive impairment and perceived stress in the patients with bipolar depression.&#xD;
  &#xD;
        The subjects are bipolar depression patients. They have been treated for bipolar depression&#xD;
        for at least four weeks but remain depressive. Participating in this study, they will&#xD;
        continue the original treatment, and will be randomized, double-blindly to receive the NMDAE&#xD;
        or placebo for 8 weeks. We will measure 6 cognitive domains (including 9 cognitive tests) and&#xD;
        quality of life at weeks 0 and 8; and assess the Perceived Stress Scale, Global Assessment of&#xD;
        Function (GAF), various scales for clinical symptoms, and side effects at weeks 0, 2, 4, 6,&#xD;
        and 8.&#xD;
  &#xD;
        The efficacies of NMDAE and placebo will be compared. Chi-square (or Fisher's exact test)&#xD;
        will be used to compare differences of categorical variables and t-test (or Mann-Whitney test&#xD;
        if the distribution is not normal) for continuous variables between treatment groups. Mean&#xD;
        changes from baseline in repeated-measure assessments will be assessed using the generalized&#xD;
        estimating equation (GEE). All p values for clinical measures will be based on two-tailed&#xD;
        tests with a significance level of 0.05.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">December 2027</completion_date>
    <primary_completion_date type="Anticipated">November 2027</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>Treatment</primary_purpose>
      <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in Visual Continuous Performance Test</measure>
      <time_frame>week 0, 8</time_frame>
      <description>Assessment of sustained attention</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Wisconsin Card Sorting Test</measure>
      <time_frame>week 0, 8</time_frame>
      <description>Assessment of abstract and shift set</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Logical Memory Test of the Wechsler Memory Scale</measure>
      <time_frame>week 0, 8</time_frame>
      <description>Assessment of episodic memory</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Digit Span</measure>
      <time_frame>week 0, 8</time_frame>
      <description>Assessment of verbal working memory</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Spatial Span</measure>
      <time_frame>week 0, 8</time_frame>
      <description>Assessment of nonverbal working memory</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Category Fluency</measure>
      <time_frame>week 0, 8</time_frame>
      <description>Assessment of speed of processing</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Trail Marking A</measure>
      <time_frame>week 0, 8</time_frame>
      <description>Assessment of speed of processing</description>
    </primary_outcome>
    <primary_outcome>
      <measure>WAIS-III Digit Symbol-Coding</measure>
      <time_frame>week 0, 8</time_frame>
      <description>Assessment of speed of processing</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) V2.0</measure>
      <time_frame>week 0, 8</time_frame>
      <description>Assessment of social cognition</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Perceived Stress Scale in Perceived Stress Scale</measure>
      <time_frame>week 0, 2, 4, 6, 8</time_frame>
      <description>Assessment of stress and anxiety symptoms Minimum value: 0, maximum value:56, the higher scores mean a worse outcome.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in Quality of life (SF-36)</measure>
      <time_frame>week 0, 8</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Global Assessmeint of Functioning</measure>
      <time_frame>Week 0, 2, 4, 6, 8</time_frame>
      <description>Assessment of global improvement. Minimum value: 1, maximum value:100, the higher scores mean a better outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Hamilton Rating Scale for Depression</measure>
      <time_frame>Week 0, 2, 4, 6, 8</time_frame>
      <description>Assessment of depressive symptoms. Minimum value: 0, maximum value:52, the higher scores mean a worse outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Montgomery-Åsberg Depression Rating Scale</measure>
      <time_frame>Week 0, 2, 4, 6, 8</time_frame>
      <description>Assessment of depressive symptoms. Minimum value: 0, maximum value:60, the higher scores mean a worse outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Young Mania Rating Scale</measure>
      <time_frame>Week 0, 2, 4, 6, 8</time_frame>
      <description>Assessment of manic symptoms. Minimum value: 0, maximum value:60, the higher scores mean a worse outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Beck Scale for Suicide Ideation</measure>
      <time_frame>Week 0, 2, 4, 6, 8</time_frame>
      <description>Assessment of Suicide Ideation. Minimum value: 0, maximum value:38, the higher scores mean a greater risk of suicide.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Clinical Global Impression Scale</measure>
      <time_frame>Week 0, 2, 4, 6, 8</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">90</enrollment>
    <condition>Bipolar I Disorder</condition>
    <arm_group>
      <arm_group_label>NMDAE</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>An NMDA enhancer</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Placebo</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>NMDAE</intervention_name>
      <description>Use of an NMDA enhancer for the treatment of bipolar depression</description>
      <arm_group_label>NMDAE</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo Cap</intervention_name>
      <description>Use of placebo as a comparator.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Are 18 to 65 years of age;&#xD;
  &#xD;
            -  Satisfy a DSM-5-TR (American Psychiatric Association) diagnosis of BD-I, current&#xD;
               episode depressed, after treatment of stable (i.e., at least 4 weeks) and adequate&#xD;
               treatment of antipsychotic (quetiapine or lurasidone) and/or mood stabilizer;&#xD;
  &#xD;
            -  Have a 17-item Hamilton Depression Rating Scale (HAMD) score ≥18 and a Young Mania&#xD;
               Rating Scale (YMRS) score ≤7 at baseline;&#xD;
  &#xD;
            -  Agree to participate in the study and provide informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Current substance abuse or history of substance dependence in the past 6 months&#xD;
  &#xD;
            -  History of epilepsy, head trauma, stroke or other serious medical or neurological&#xD;
               illness which may interfere with the study&#xD;
  &#xD;
            -  Schizophrenia or other psychotic disorder&#xD;
  &#xD;
            -  Moderate-severe suicidal risks&#xD;
  &#xD;
            -  Severe cognitive impairment&#xD;
  &#xD;
            -  Clinically significant laboratory screening tests (including blood routine,&#xD;
               biochemical tests)&#xD;
  &#xD;
            -  Pregnancy or lactation;&#xD;
  &#xD;
            -  Inability to follow protocol&#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_contact>
      <last_name>Hsien-Yuan Lane Lane, M.D., Ph.D</last_name>
      <phone>886 4 22052121</phone>
      <phone_ext>1855</phone_ext>
      <email>hylane@gmail.com</email>
    </overall_contact>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 28, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>August 3, 2023</last_update_submitted>
    <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Bipolar I disorder</keyword>
    <keyword>Bipolar depression</keyword>
    <keyword>NMDA</keyword>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05977023
  org study id: CMUH111-REC2-222
  nct id: NCT05977023
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  At present, the treatment of Bipolar I disorder (BD-I), especially its depressive episode
        (bipolar depression), is still limited, because there is no effective treatment for the
        associated cognitive impairment and perceived stress. NMDA receptor (NMDAR) dysfunction is
        associated with BD-I, particularly its cognitive impairment and perceived stress. This study
        aims to examine the efficacy and safety of an NMDA enhancer (NMDAE) in the treatment of
        cognitive impairment and perceived stress in the patients with bipolar depression.
  Bipolar I disorder (BD-I) is a severe brain disorder. At present, the treatment of BD-I,
        especially its depressive episode (bipolar depression), is still limited, because there is no
        effective treatment for the associated cognitive impairment and perceived stress. This study
        aims to examine the efficacy and safety of an NMDA enhancer (NMDAE) in the treatment of
        cognitive impairment and perceived stress in the patients with bipolar depression.
  
        The subjects are bipolar depression patients. They have been treated for bipolar depression
        for at least four weeks but remain depressive. Participating in this study, they will
        continue the original treatment, and will be randomized, double-blindly to receive the NMDAE
        or placebo for 8 weeks. We will measure 6 cognitive domains (including 9 cognitive tests) and
        quality of life at weeks 0 and 8; and assess the Perceived Stress Scale, Global Assessment of
        Function (GAF), various scales for clinical symptoms, and side effects at weeks 0, 2, 4, 6,
        and 8.
  
        The efficacies of NMDAE and placebo will be compared. Chi-square (or Fisher's exact test)
        will be used to compare differences of categorical variables and t-test (or Mann-Whitney test
        if the distribution is not normal) for continuous variables between treatment groups. Mean
        changes from baseline in repeated-measure assessments will be assessed using the generalized
        estimating equation (GEE). All p values for clinical measures will be based on two-tailed
        tests with a significance level of 0.05.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  measure: Change in Visual Continuous Performance Test
  time frame: week 0, 8
  description: Assessment of sustained attention
  measure: Change in Wisconsin Card Sorting Test
  time frame: week 0, 8
  description: Assessment of abstract and shift set
  measure: Change in Logical Memory Test of the Wechsler Memory Scale
  time frame: week 0, 8
  description: Assessment of episodic memory
  measure: Digit Span
  time frame: week 0, 8
  description: Assessment of verbal working memory
  measure: Spatial Span
  time frame: week 0, 8
  description: Assessment of nonverbal working memory
  measure: Category Fluency
  time frame: week 0, 8
  description: Assessment of speed of processing
  measure: Trail Marking A
  time frame: week 0, 8
  description: Assessment of speed of processing
  measure: WAIS-III Digit Symbol-Coding
  time frame: week 0, 8
  description: Assessment of speed of processing
  measure: Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) V2.0
  time frame: week 0, 8
  description: Assessment of social cognition
  measure: Change in Perceived Stress Scale in Perceived Stress Scale
  time frame: week 0, 2, 4, 6, 8
  description: Assessment of stress and anxiety symptoms Minimum value: 0, maximum value:56, the higher scores mean a worse outcome.
  measure: Change in Quality of life (SF-36)
  time frame: week 0, 8
  measure: Change in Global Assessmeint of Functioning
  time frame: Week 0, 2, 4, 6, 8
  description: Assessment of global improvement. Minimum value: 1, maximum value:100, the higher scores mean a better outcome.
  measure: Change in Hamilton Rating Scale for Depression
  time frame: Week 0, 2, 4, 6, 8
  description: Assessment of depressive symptoms. Minimum value: 0, maximum value:52, the higher scores mean a worse outcome.
  measure: Change in Montgomery-Åsberg Depression Rating Scale
  time frame: Week 0, 2, 4, 6, 8
  description: Assessment of depressive symptoms. Minimum value: 0, maximum value:60, the higher scores mean a worse outcome.
  measure: Change in Young Mania Rating Scale
  time frame: Week 0, 2, 4, 6, 8
  description: Assessment of manic symptoms. Minimum value: 0, maximum value:60, the higher scores mean a worse outcome.
  measure: Change in Beck Scale for Suicide Ideation
  time frame: Week 0, 2, 4, 6, 8
  description: Assessment of Suicide Ideation. Minimum value: 0, maximum value:38, the higher scores mean a greater risk of suicide.
  measure: Change in Clinical Global Impression Scale
  time frame: Week 0, 2, 4, 6, 8
  arm group label: NMDAE
  arm group type: Experimental
  description: An NMDA enhancer
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Placebo
  intervention type: Drug
  intervention name: NMDAE
  description: Use of an NMDA enhancer for the treatment of bipolar depression
  arm group label: NMDAE
  intervention type: Drug
  intervention name: Placebo Cap
  description: Use of placebo as a comparator.
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Hsien-Yuan Lane Lane, M.D., Ph.D
  phone: 886 4 22052121
  phone ext: 1855
  email: hylane@gmail.com
  responsible party type: Sponsor