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/NCT06021197</url>
    </required_header>
    <id_info>
      <org_study_id>CMUH111-REC3-228</org_study_id>
      <nct_id>NCT06021197</nct_id>
    </id_info>
    <brief_title>NMDA-enhancing Treatment for Cognitive Dysfunction of Schizophrenia</brief_title>
    <official_title>NMDA-enhancing Treatment for Cognitive Dysfunction of Schizophrenia Patients During Symptomatic Remission</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, Taiwan</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>China Medical University Hospital</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Cognitive impairment, the core psychopathology of schizophrenia, usually persists in&#xD;
        schizophrenia patients even during symptomatic remission. While cognitive impairment&#xD;
        associated with schizophrenia (CIAS) is an important therapeutic target, hypofunction of&#xD;
        N-methyl-D-aspartate receptor (NMDAR) is a key factor of CIAS. This study aims to examine the&#xD;
        efficacy and safety of an NMDA-enhancer (NMDAE) for the treatment of CIAS in schizophrenia&#xD;
        patients during symptomatic remission.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Cognitive impairment, the core psychopathology and the outcome determinant of schizophrenia,&#xD;
        usually persists in schizophrenia patients even during symptomatic remission. Cognitive&#xD;
        impairment associated with schizophrenia (CIAS) is an important therapeutic target; and&#xD;
        hypofunction of N-methyl-D-aspartate receptor (NMDAR) is a key factor of CIAS. Whether&#xD;
        NMDAR-enhancing treatment can truly improve cognitive function needs to be tested in&#xD;
        schizophrenia patients during symptomatic remission. This study aims to examine the efficacy&#xD;
        and safety of an NMDA-enhancer (NMDAE) for the treatment of CIAS in schizophrenia patients&#xD;
        during symptomatic remission.&#xD;
  &#xD;
        The subjects are the patients with schizophrenia during symptomatic remission. They keep&#xD;
        their original treatment and are randomly, double-blindly assigned into two treatment groups&#xD;
        for 12 weeks: (1) NMDAE, or (2) placebo. At weeks 0 and 12, 7 cognitive domains will be&#xD;
        measured. At weeks 0, 4, 8, and 12, Global Assessment of Function, Quality of Life Scale,&#xD;
        various clinical-symptom rating scales, and side effects scales will be measured too.&#xD;
  &#xD;
        Chi-square (or Fisher's exact test) will be used to compare differences of categorical&#xD;
        variables and t-test (or Mann-Whitney test if the distribution is not normal) for continuous&#xD;
        variables between treatment groups. Mean changes from baseline in repeated-measure&#xD;
        assessments will be assessed using the generalized estimating equation (GEE). All p values&#xD;
        for clinical measures will be based on two-tailed tests with a significance level of 0.05.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">March 2028</completion_date>
    <primary_completion_date type="Anticipated">December 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 of cognitive function composite</measure>
      <time_frame>Week 0, 12</time_frame>
      <description>Ten tests for assessment of 7 cognitive domains:&#xD;
  speed of processing (assessed by Category Fluency, Trail Marking A, Wechsler Adult Intelligence Scale(WAIS)-III Digit Symbol-Coding)&#xD;
  sustained attention (Continuous Performance Test)&#xD;
  working memory: verbal (digit span) and nonverbal (spatial span)&#xD;
  verbal learning and memory (WMS-III, word listing)&#xD;
  visual learning and memory (WMS-III, visual reproduction)&#xD;
  reasoning and problem solving (WISC-III, Maze)&#xD;
  social cognition (MSCEIT Version 2)&#xD;
  For the domain (a. and c.) with more than one test, a composite T score will be calculated by standardizing the average of each T score. Furthermore, a global composite score (for all seven domains) and a neurocognitive composite score (for the first 6 domains) will be also calculated by standardizing the average of the T score (Lane HY et al, JAMA Psychiatry 2013)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change of Global Assessment of Functioning composite</measure>
      <time_frame>week 0, 4, 8, 12</time_frame>
      <description>Assessment of social, occupational, and psychological function. Minimum value: 1, maximum value:100, the higher scores mean better function.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change of Quality of Life Scale</measure>
      <time_frame>week 0, 4, 8, 12</time_frame>
      <description>Assessment of life quality. Minimum value: 0, maximum value:126, the higher scores mean a better outcome.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Change of Positive and Negative Syndrome Scale (PANSS)</measure>
      <time_frame>week 0, 4, 8, 12</time_frame>
      <description>Assessment of overall symptoms. Minimum value: 30, maximum value:210, the higher scores mean a worse outcome.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change of scales for the Assessment of Negative Symptoms (SANS) total score</measure>
      <time_frame>week 0, 4, 8, 12</time_frame>
      <description>Assessment of negative symptoms. Minimum value: 0, maximum value:100, the higher scores mean a worse outcome.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change of Positive subscale of PANSS</measure>
      <time_frame>week 0, 4, 8, 12</time_frame>
      <description>Assessment of positive symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change of Negative subscale of PANSS</measure>
      <time_frame>week 0, 4, 8, 12</time_frame>
      <description>Assessment of negative symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change of General Psychopathology subscale of PANSS</measure>
      <time_frame>week 0, 4, 8, 12</time_frame>
      <description>Assessment of general psychopathology. Minimum value: 16, maximum value:112, the higher scores mean a worse outcome.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change of Clinical Global Impression</measure>
      <time_frame>week 0, 4, 8, 12</time_frame>
      <description>Assessment of general impression. Minimum value: 1, maximum value:7, the higher scores mean a worse outcome.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change of Hamilton Rating Scale for Depression</measure>
      <time_frame>week 0, 4, 8, 12</time_frame>
      <description>Assessment of depressive symptoms. Minimum value: 0, maximum value:52, the higher scores mean a worse outcome.</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">90</enrollment>
    <condition>Schizophrenia</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 CIAS</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;
            -  Have a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text&#xD;
               Revision (DSM-5 -TR) diagnosis of schizophrenia&#xD;
  &#xD;
            -  Fulfill the Remission in Schizophrenia Working Group (RSWG) criteria for remission&#xD;
               (Andreasen et al., 2005): each of eight items (delusions, unusual thought content,&#xD;
               hallucinatory behavior, conceptual disorganization, mannerisms/posturing, blunted&#xD;
               affect, passive/apathetic social withdrawal, and lack of spontaneity and flow of&#xD;
               conversation) in the Positive and Negative Syndrome Scale (PANSS) (Kay et al., 1987)&#xD;
               scoring 3 or lower for 6 months or longer; in addition, have a baseline total score of&#xD;
               59 or lower in the PANSS&#xD;
  &#xD;
            -  Are physically healthy and laboratory assessments (including blood routine,&#xD;
               biochemical tests) are clinically insignificant;&#xD;
  &#xD;
            -  Have been keeping a fixed dose of antipsychotics (excluding clozapine) for at least 6&#xD;
               months, and that is not allowed to change during the 12-week study period&#xD;
  &#xD;
            -  Have sufficient education to communicate effectively and are capable of completing the&#xD;
               assessments of the study&#xD;
  &#xD;
            -  Agree to participate in the study and provide written informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  DSM-5-TR diagnosis of intellectual disability or substance (including alcohol) use&#xD;
               disorder&#xD;
  &#xD;
            -  History of epilepsy, head trauma, or serious medical or central nervous system&#xD;
               diseases (other than schizophrenia) which may interfere with the study&#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, M.D., Ph.D</last_name>
      <phone>886 4 22052121</phone>
      <phone_ext>11855</phone_ext>
      <email>hylane@gmail.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Department of Psychiatry, China Medical University Hospital</name>
        <address>
          <city>Taichung</city>
          <country>Taiwan</country>
        </address>
      </facility>
      <contact>
        <last_name>Hsien-Yuan Lane, M.D., Ph.D</last_name>
        <phone>886 4 22052121</phone>
        <phone_ext>11855</phone_ext>
        <email>hylane@gmail.com</email>
      </contact>
    </location>
    <location_countries>
      <country>Taiwan</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 28, 2023</study_first_submitted>
    <study_first_submitted_qc>August 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>September 4, 2023</last_update_submitted>
    <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Schizophrenia</keyword>
    <keyword>NMDA</keyword>
    <keyword>Symptomatic remission</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Schizophrenia</mesh_term>
      <mesh_term>Cognitive Dysfunction</mesh_term>
    </condition_browse>
    <!-- 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/NCT06021197
  org study id: CMUH111-REC3-228
  nct id: NCT06021197
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  Cognitive impairment, the core psychopathology of schizophrenia, usually persists in
        schizophrenia patients even during symptomatic remission. While cognitive impairment
        associated with schizophrenia (CIAS) is an important therapeutic target, hypofunction of
        N-methyl-D-aspartate receptor (NMDAR) is a key factor of CIAS. This study aims to examine the
        efficacy and safety of an NMDA-enhancer (NMDAE) for the treatment of CIAS in schizophrenia
        patients during symptomatic remission.
  Cognitive impairment, the core psychopathology and the outcome determinant of schizophrenia,
        usually persists in schizophrenia patients even during symptomatic remission. Cognitive
        impairment associated with schizophrenia (CIAS) is an important therapeutic target; and
        hypofunction of N-methyl-D-aspartate receptor (NMDAR) is a key factor of CIAS. Whether
        NMDAR-enhancing treatment can truly improve cognitive function needs to be tested in
        schizophrenia patients during symptomatic remission. This study aims to examine the efficacy
        and safety of an NMDA-enhancer (NMDAE) for the treatment of CIAS in schizophrenia patients
        during symptomatic remission.
  
        The subjects are the patients with schizophrenia during symptomatic remission. They keep
        their original treatment and are randomly, double-blindly assigned into two treatment groups
        for 12 weeks: (1) NMDAE, or (2) placebo. At weeks 0 and 12, 7 cognitive domains will be
        measured. At weeks 0, 4, 8, and 12, Global Assessment of Function, Quality of Life Scale,
        various clinical-symptom rating scales, and side effects scales will be measured too.
  
        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 of cognitive function composite
  time frame: Week 0, 12
  description: Ten tests for assessment of 7 cognitive domains:
  speed of processing (assessed by Category Fluency, Trail Marking A, Wechsler Adult Intelligence Scale(WAIS)-III Digit Symbol-Coding)
  sustained attention (Continuous Performance Test)
  working memory: verbal (digit span) and nonverbal (spatial span)
  verbal learning and memory (WMS-III, word listing)
  visual learning and memory (WMS-III, visual reproduction)
  reasoning and problem solving (WISC-III, Maze)
  social cognition (MSCEIT Version 2)
  For the domain (a. and c.) with more than one test, a composite T score will be calculated by standardizing the average of each T score. Furthermore, a global composite score (for all seven domains) and a neurocognitive composite score (for the first 6 domains) will be also calculated by standardizing the average of the T score (Lane HY et al, JAMA Psychiatry 2013)
  measure: Change of Global Assessment of Functioning composite
  time frame: week 0, 4, 8, 12
  description: Assessment of social, occupational, and psychological function. Minimum value: 1, maximum value:100, the higher scores mean better function.
  measure: Change of Quality of Life Scale
  time frame: week 0, 4, 8, 12
  description: Assessment of life quality. Minimum value: 0, maximum value:126, the higher scores mean a better outcome.
  measure: Change of Positive and Negative Syndrome Scale (PANSS)
  time frame: week 0, 4, 8, 12
  description: Assessment of overall symptoms. Minimum value: 30, maximum value:210, the higher scores mean a worse outcome.
  measure: Change of scales for the Assessment of Negative Symptoms (SANS) total score
  time frame: week 0, 4, 8, 12
  description: Assessment of negative symptoms. Minimum value: 0, maximum value:100, the higher scores mean a worse outcome.
  measure: Change of Positive subscale of PANSS
  time frame: week 0, 4, 8, 12
  description: Assessment of positive symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome.
  measure: Change of Negative subscale of PANSS
  time frame: week 0, 4, 8, 12
  description: Assessment of negative symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome.
  measure: Change of General Psychopathology subscale of PANSS
  time frame: week 0, 4, 8, 12
  description: Assessment of general psychopathology. Minimum value: 16, maximum value:112, the higher scores mean a worse outcome.
  measure: Change of Clinical Global Impression
  time frame: week 0, 4, 8, 12
  description: Assessment of general impression. Minimum value: 1, maximum value:7, the higher scores mean a worse outcome.
  measure: Change of Hamilton Rating Scale for Depression
  time frame: week 0, 4, 8, 12
  description: Assessment of depressive symptoms. Minimum value: 0, maximum value:52, the higher scores mean a worse outcome.
  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 CIAS
  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, M.D., Ph.D
  phone: 886 4 22052121
  phone ext: 11855
  email: hylane@gmail.com
  facility: 
  contact: 
  country: Taiwan
  responsible party type: Sponsor
  mesh term: Schizophrenia
  mesh term: Cognitive Dysfunction