<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/NCT04470037</url>
  </required_header>
  <id_info>
    <org_study_id>CMUH105-REC1-023</org_study_id>
    <nct_id>NCT04470037</nct_id>
  </id_info>
  <brief_title>Multidisciplinary Study of Novel NMDA Modulation for Neurodegenerative Disorder</brief_title>
  <official_title>Multidisciplinary Study of Novel NMDA Modulation for Neurodegenerative Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>China Medical University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Science and Technology, Taiwan</agency>
      <agency_class>Other</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>
      Alzheimer's disease (AD) and Parkinson's disease (PD) are currently the leading&#xD;
      neurodegenerative disorders. Considering the fact that aged population is rapidly growing, it&#xD;
      has become a critical issue to find more effective medications for these two disorders. The&#xD;
      aim of this project is to examine the effectiveness and safety of DAAOI-P treatment for PD&#xD;
      with dementia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Alzheimer's disease (AD) and Parkinson's disease (PD) are currently the leading&#xD;
      neurodegenerative disorders. Despite some therapeutic benefits from the medications targeting&#xD;
      at cholinergic and dopaminergic pathways in AD and PD respectively, it remains far away from&#xD;
      a satisfied treatment goal. DAAOI-P is a D-amino acid oxidase (DAAO) inhibitor and an agent&#xD;
      specific to facilitate NMDA receptor subunit 1 (NR1). The investigators have demonstrated&#xD;
      that NMDA-enhancement can help PD-D patients. The aim of this project is to examine the&#xD;
      effectiveness and safety of DAAOI-P treatment for PD with dementia. In addition to evaluating&#xD;
      clinical treatment response, multidisciplinary examinations, including&#xD;
      electroencephalography, transcranial magnetic stimulation, magnetic resonance imaging (MRI),&#xD;
      and psychophysical methods to analyze the changes in perceptual sensitivity to faces, emotion&#xD;
      expressions, and biological motion recognition will be arranged to elucidate the underlying&#xD;
      mechanism of NMDA modulation in neurodegenerative disorder.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 2016</start_date>
  <completion_date type="Anticipated">March 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2024</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The improvement of gait and neuropsychiatric symptoms</measure>
    <time_frame>week 0, 8, 16, 24</time_frame>
    <description>Change in Unified Parkinson's Disease Rating Scale (UPDRS)&#xD;
UPDRS: Unified Parkinson's Disease Rating Scale Minimum value: 0 Maximum value: 199 The higher score means a worse outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Gait function</measure>
    <time_frame>week 0, 8, 16, 24</time_frame>
    <description>The Cyclogram of Gait&#xD;
Minimum value: 0 Maximum value: 100 The higher score means a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fall assessment</measure>
    <time_frame>week 0, 8, 16, 24</time_frame>
    <description>The fall assessment test of China Medical University Hospital&#xD;
Minimum value: 0 Maximum value: 10 The higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive function</measure>
    <time_frame>week 0, 8, 16, 24</time_frame>
    <description>Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)&#xD;
ADAS-Cog: Alzheimer's Disease Assessment Scale-Cognitive Subscale Minimum value: 0 Maximum value: 70 The higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropsychiatric symptoms</measure>
    <time_frame>week 0, 8, 16, 24</time_frame>
    <description>Change in Neuropsychiatry Inventory (NPI)&#xD;
NPI: Neuropsychiatry Inventory Minimum value: 0 Maximum value: 144 The higher score means a worse outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The improvement of Parkinson's disease</measure>
    <time_frame>week 0, 8, 16, 24</time_frame>
    <description>Change in The 39-item Parkinson's Disease Questionnaire (PDQ-39)&#xD;
PDQ-39: The 39-item Parkinson's Disease Questionnaire Minimum value: 0 Maximum value: 156 The higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Behavioral Pathology of dementia</measure>
    <time_frame>week 0, 8, 16, 24</time_frame>
    <description>Change in Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD)&#xD;
Behave-AD: Behavioral Pathology in Alzheimer's Disease Rating Scale Minimum value: 0 Maximum value: 75 The higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of dementia</measure>
    <time_frame>week 0, 8, 16, 24</time_frame>
    <description>Change in Clinical Dementia Rating (CDR)&#xD;
CDR: Clinical Dementia Rating Minimum value: 0 Maximum value: 5 The higher score means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuroimaging examinations</measure>
    <time_frame>week 0, 24</time_frame>
    <description>Neuroimaging examinations contains: (1) Structural MRI, (2) Resting-state fMRI, and (3) Working memory fMRI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Face perception</measure>
    <time_frame>week 0, 8, 16, 24</time_frame>
    <description>Changes in perceptual discriminability (d-prime index)&#xD;
Minimum value: 0 (chance level); Maximum value: 3.0 (nearly perfect)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emotion recognition and imitation</measure>
    <time_frame>week 0, 8, 16, 24</time_frame>
    <description>Changes in emotion recognition accuracy and imitation probability&#xD;
Minimum value: 0%; Maximum value: 100% (Higher score indicate a better outcome)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transcranial magnetic stimulation</measure>
    <time_frame>week 0, 8, 16, 24</time_frame>
    <description>Change in Transcranial Magnetic Stimulation (TMS) assessments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Electroencephalography</measure>
    <time_frame>week 0, 8, 16, 24</time_frame>
    <description>Changes in Mismatch negativity (MMN)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Parkinson's Disease With Dementia</condition>
  <arm_group>
    <arm_group_label>DAAOI-P</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DAAOI-P 250-1500mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Starch pill</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DAAOI-P</intervention_name>
    <description>DAAOI-P 250-1500mg</description>
    <arm_group_label>DAAOI-P</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>starch pill</description>
    <arm_group_label>Starch pill</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  PD-D will be diagnosed according to the criteria proposed by Movement Disorder Society&#xD;
             task force statement. (Emre et al. 2007) . The following wordings are modified from&#xD;
             the task force statement. I. Core features&#xD;
&#xD;
               1. Diagnosis of PD according to Queen Square Brain Bank criteria&#xD;
&#xD;
               2. A dementia syndrome with insidious onset and slow progression, developing within&#xD;
                  the context of established PD and diagnosed by history, clinical, and mental&#xD;
                  examination, defined as:&#xD;
&#xD;
                    -  Impairment in more than one cognitive domain&#xD;
&#xD;
                    -  Representing a decline from premorbid level&#xD;
&#xD;
                    -  Deficits severe enough to impair daily life, independent of the impairment&#xD;
                       ascribable to motor or autonomic symptoms&#xD;
&#xD;
                    -  MMSE score between 10-26.&#xD;
&#xD;
        II. Associated clinical features&#xD;
&#xD;
          1. Cognitive features: Impaired attention, executive functions, visuo-spatial functions&#xD;
             or memory. Core functions of language are largely preserved.&#xD;
&#xD;
          2. Behavioral features:&#xD;
&#xD;
               -  Apathy&#xD;
&#xD;
               -  Changes in personality and mood&#xD;
&#xD;
               -  Hallucination• Delusions&#xD;
&#xD;
               -  Excessive daytime sleepiness&#xD;
&#xD;
        III. Features which do not exclude PD-D, but make the diagnosis uncertain&#xD;
&#xD;
          -  Co-existence of any other abnormality which may by itself cause cognitive impairment,&#xD;
             but judged not to be the cause of dementia.&#xD;
&#xD;
          -  Time interval between the development of motor and cognitive symptoms is uncertain&#xD;
&#xD;
        IV. Features suggesting other conditions or diseases as cause of mental impairment, which,&#xD;
        when present make it impossible to reliably diagnose PD-D&#xD;
&#xD;
          -  Cognitive and behavioral symptoms appearing solely in the context of other conditions&#xD;
             such as:&#xD;
&#xD;
               1. Acute confusion due to systemic illnesses or drug intoxication.&#xD;
&#xD;
               2. Major depression&#xD;
&#xD;
          -  Features compatible with &quot;Probable Vascular dementia&quot; criteria according to&#xD;
             NINDS-AIREN Criteria for the diagnosis of probable and possible PD-D [Probable PD-D]&#xD;
             Both core features must be present. In associated clinical features, typical profile&#xD;
             of cognitive deficits should be present in at least 2 of the 4 core cognitive domains.&#xD;
             The presence of at least one behavioral symptom supports the diagnosis of probable&#xD;
             PD-D. None of group III and IV features is present. [Possible PD-D] Both core features&#xD;
             must be present. In associated clinical features, the cognitive impairment is atypical&#xD;
             in one or more domains. The behavioral symptoms are not necessary to be present. One&#xD;
             or more of the group III features may be present. No group IV feature is allowed to be&#xD;
             present.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with uncontrollable malignancy, severe heart failure, uremia under&#xD;
             hemodialysis, or decompensated liver cirrhosis.&#xD;
&#xD;
          2. Patients taking anticholinergics within 30 days of recruitment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lane</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Psychiatry, China Medical University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hsien-Yuan Lane, M.D., Ph.D</last_name>
    <phone>886 921 067260</phone>
    <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>
    <status>Recruiting</status>
    <contact>
      <last_name>Hsien-Yuan Lane, M.D., Ph.D</last_name>
      <phone>886 921 067260</phone>
      <email>hylane@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>August 5, 2023</last_update_submitted>
  <last_update_submitted_qc>August 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>China Medical University Hospital</investigator_affiliation>
    <investigator_full_name>Hsien-Yuan Lane</investigator_full_name>
    <investigator_title>Director, Department of psychiatry, China Medical University Hospital</investigator_title>
  </responsible_party>
  <keyword>Parkinson's disease</keyword>
  <keyword>Dementia</keyword>
  <keyword>NMDA</keyword>
  <keyword>DAAOI</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
    <mesh_term>Dementia</mesh_term>
    <mesh_term>Neurodegenerative Diseases</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/NCT04470037
org study id: CMUH105-REC1-023
nct id: NCT04470037
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Alzheimer's disease (AD) and Parkinson's disease (PD) are currently the leading
      neurodegenerative disorders. Considering the fact that aged population is rapidly growing, it
      has become a critical issue to find more effective medications for these two disorders. The
      aim of this project is to examine the effectiveness and safety of DAAOI-P treatment for PD
      with dementia.
Alzheimer's disease (AD) and Parkinson's disease (PD) are currently the leading
      neurodegenerative disorders. Despite some therapeutic benefits from the medications targeting
      at cholinergic and dopaminergic pathways in AD and PD respectively, it remains far away from
      a satisfied treatment goal. DAAOI-P is a D-amino acid oxidase (DAAO) inhibitor and an agent
      specific to facilitate NMDA receptor subunit 1 (NR1). The investigators have demonstrated
      that NMDA-enhancement can help PD-D patients. The aim of this project is to examine the
      effectiveness and safety of DAAOI-P treatment for PD with dementia. In addition to evaluating
      clinical treatment response, multidisciplinary examinations, including
      electroencephalography, transcranial magnetic stimulation, magnetic resonance imaging (MRI),
      and psychophysical methods to analyze the changes in perceptual sensitivity to faces, emotion
      expressions, and biological motion recognition will be arranged to elucidate the underlying
      mechanism of NMDA modulation in neurodegenerative disorder.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The improvement of gait and neuropsychiatric symptoms
time frame: week 0, 8, 16, 24
description: Change in Unified Parkinson's Disease Rating Scale (UPDRS)
UPDRS: Unified Parkinson's Disease Rating Scale Minimum value: 0 Maximum value: 199 The higher score means a worse outcome.
measure: Gait function
time frame: week 0, 8, 16, 24
description: The Cyclogram of Gait
Minimum value: 0 Maximum value: 100 The higher score means a better outcome.
measure: Fall assessment
time frame: week 0, 8, 16, 24
description: The fall assessment test of China Medical University Hospital
Minimum value: 0 Maximum value: 10 The higher score means a worse outcome.
measure: Cognitive function
time frame: week 0, 8, 16, 24
description: Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
ADAS-Cog: Alzheimer's Disease Assessment Scale-Cognitive Subscale Minimum value: 0 Maximum value: 70 The higher score means a worse outcome.
measure: Neuropsychiatric symptoms
time frame: week 0, 8, 16, 24
description: Change in Neuropsychiatry Inventory (NPI)
NPI: Neuropsychiatry Inventory Minimum value: 0 Maximum value: 144 The higher score means a worse outcome
measure: The improvement of Parkinson's disease
time frame: week 0, 8, 16, 24
description: Change in The 39-item Parkinson's Disease Questionnaire (PDQ-39)
PDQ-39: The 39-item Parkinson's Disease Questionnaire Minimum value: 0 Maximum value: 156 The higher score means a worse outcome.
measure: Behavioral Pathology of dementia
time frame: week 0, 8, 16, 24
description: Change in Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD)
Behave-AD: Behavioral Pathology in Alzheimer's Disease Rating Scale Minimum value: 0 Maximum value: 75 The higher score means a worse outcome.
measure: Severity of dementia
time frame: week 0, 8, 16, 24
description: Change in Clinical Dementia Rating (CDR)
CDR: Clinical Dementia Rating Minimum value: 0 Maximum value: 5 The higher score means a worse outcome.
measure: Neuroimaging examinations
time frame: week 0, 24
description: Neuroimaging examinations contains: (1) Structural MRI, (2) Resting-state fMRI, and (3) Working memory fMRI.
measure: Face perception
time frame: week 0, 8, 16, 24
description: Changes in perceptual discriminability (d-prime index)
Minimum value: 0 (chance level); Maximum value: 3.0 (nearly perfect)
measure: Emotion recognition and imitation
time frame: week 0, 8, 16, 24
description: Changes in emotion recognition accuracy and imitation probability
Minimum value: 0%; Maximum value: 100% (Higher score indicate a better outcome)
measure: Transcranial magnetic stimulation
time frame: week 0, 8, 16, 24
description: Change in Transcranial Magnetic Stimulation (TMS) assessments
measure: Electroencephalography
time frame: week 0, 8, 16, 24
description: Changes in Mismatch negativity (MMN)
arm group label: DAAOI-P
arm group type: Experimental
description: DAAOI-P 250-1500mg
arm group label: Starch pill
arm group type: Placebo Comparator
intervention type: Drug
intervention name: DAAOI-P
description: DAAOI-P 250-1500mg
arm group label: DAAOI-P
intervention type: Drug
intervention name: Placebo
description: starch pill
arm group label: Starch pill
criteria: 
gender: All
minimum age: 50 Years
maximum age: 90 Years
healthy volunteers: No
last name: Lane
role: Principal Investigator
affiliation: Department of Psychiatry, China Medical University Hospital
last name: Hsien-Yuan Lane, M.D., Ph.D
phone: 886 921 067260
email: hylane@gmail.com
facility: 
status: Recruiting
contact: 
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: China Medical University Hospital
investigator full name: Hsien-Yuan Lane
investigator title: Director, Department of psychiatry, China Medical University Hospital
mesh term: Parkinson Disease
mesh term: Dementia
mesh term: Neurodegenerative Diseases