search
Back to results

Multidisciplinary Study of Novel NMDA Modulation for Neurodegenerative Disorder

Primary Purpose

Parkinson's Disease With Dementia

Status
Recruiting
Phase
Phase 2
Locations
Taiwan
Study Type
Interventional
Intervention
DAAOI-P
Placebo
Sponsored by
China Medical University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson's Disease With Dementia focused on measuring Parkinson's disease, Dementia, NMDA, DAAOI

Eligibility Criteria

50 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • PD-D will be diagnosed according to the criteria proposed by Movement Disorder Society task force statement. (Emre et al. 2007) . The following wordings are modified from the task force statement. I. Core features

    1. Diagnosis of PD according to Queen Square Brain Bank criteria
    2. A dementia syndrome with insidious onset and slow progression, developing within the context of established PD and diagnosed by history, clinical, and mental examination, defined as:

      • Impairment in more than one cognitive domain
      • Representing a decline from premorbid level
      • Deficits severe enough to impair daily life, independent of the impairment ascribable to motor or autonomic symptoms
      • MMSE score between 10-26.

II. Associated clinical features

  1. Cognitive features: Impaired attention, executive functions, visuo-spatial functions or memory. Core functions of language are largely preserved.
  2. Behavioral features:

    • Apathy
    • Changes in personality and mood
    • Hallucination• Delusions
    • Excessive daytime sleepiness

III. Features which do not exclude PD-D, but make the diagnosis uncertain

  • Co-existence of any other abnormality which may by itself cause cognitive impairment, but judged not to be the cause of dementia.
  • Time interval between the development of motor and cognitive symptoms is uncertain

IV. Features suggesting other conditions or diseases as cause of mental impairment, which, when present make it impossible to reliably diagnose PD-D

  • Cognitive and behavioral symptoms appearing solely in the context of other conditions such as:

    1. Acute confusion due to systemic illnesses or drug intoxication.
    2. Major depression
  • Features compatible with "Probable Vascular dementia" criteria according to NINDS-AIREN Criteria for the diagnosis of probable and possible PD-D [Probable PD-D] Both core features must be present. In associated clinical features, typical profile of cognitive deficits should be present in at least 2 of the 4 core cognitive domains. The presence of at least one behavioral symptom supports the diagnosis of probable PD-D. None of group III and IV features is present. [Possible PD-D] Both core features must be present. In associated clinical features, the cognitive impairment is atypical in one or more domains. The behavioral symptoms are not necessary to be present. One or more of the group III features may be present. No group IV feature is allowed to be present.

Exclusion Criteria:

  1. Patients with uncontrollable malignancy, severe heart failure, uremia under hemodialysis, or decompensated liver cirrhosis.
  2. Patients taking anticholinergics within 30 days of recruitment.

Sites / Locations

  • Department of Psychiatry, China Medical University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

DAAOI-P

Starch pill

Arm Description

DAAOI-P 250-1500mg

Outcomes

Primary Outcome Measures

The improvement of gait and neuropsychiatric symptoms
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.

Secondary Outcome Measures

Gait function
The Cyclogram of Gait Minimum value: 0 Maximum value: 100 The higher score means a better outcome.
Fall assessment
The fall assessment test of China Medical University Hospital Minimum value: 0 Maximum value: 10 The higher score means a worse outcome.
Cognitive function
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.
Neuropsychiatric symptoms
Change in Neuropsychiatry Inventory (NPI) NPI: Neuropsychiatry Inventory Minimum value: 0 Maximum value: 144 The higher score means a worse outcome
The improvement of Parkinson's disease
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.
Behavioral Pathology of dementia
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.
Severity of dementia
Change in Clinical Dementia Rating (CDR) CDR: Clinical Dementia Rating Minimum value: 0 Maximum value: 5 The higher score means a worse outcome.
Neuroimaging examinations
Neuroimaging examinations contains: (1) Structural MRI, (2) Resting-state fMRI, and (3) Working memory fMRI.
Face perception
Changes in perceptual discriminability (d-prime index) Minimum value: 0 (chance level); Maximum value: 3.0 (nearly perfect)
Emotion recognition and imitation
Changes in emotion recognition accuracy and imitation probability Minimum value: 0%; Maximum value: 100% (Higher score indicate a better outcome)
Transcranial magnetic stimulation
Change in Transcranial Magnetic Stimulation (TMS) assessments
Electroencephalography
Changes in Mismatch negativity (MMN)

Full Information

First Posted
May 26, 2020
Last Updated
August 5, 2023
Sponsor
China Medical University Hospital
Collaborators
Ministry of Science and Technology, Taiwan
search

1. Study Identification

Unique Protocol Identification Number
NCT04470037
Brief Title
Multidisciplinary Study of Novel NMDA Modulation for Neurodegenerative Disorder
Official Title
Multidisciplinary Study of Novel NMDA Modulation for Neurodegenerative Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 2016 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
China Medical University Hospital
Collaborators
Ministry of Science and Technology, Taiwan

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease With Dementia
Keywords
Parkinson's disease, Dementia, NMDA, DAAOI

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
DAAOI-P
Arm Type
Experimental
Arm Description
DAAOI-P 250-1500mg
Arm Title
Starch pill
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
DAAOI-P
Intervention Description
DAAOI-P 250-1500mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
starch pill
Primary Outcome Measure Information:
Title
The improvement of gait and neuropsychiatric symptoms
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.
Time Frame
week 0, 8, 16, 24
Secondary Outcome Measure Information:
Title
Gait function
Description
The Cyclogram of Gait Minimum value: 0 Maximum value: 100 The higher score means a better outcome.
Time Frame
week 0, 8, 16, 24
Title
Fall assessment
Description
The fall assessment test of China Medical University Hospital Minimum value: 0 Maximum value: 10 The higher score means a worse outcome.
Time Frame
week 0, 8, 16, 24
Title
Cognitive function
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.
Time Frame
week 0, 8, 16, 24
Title
Neuropsychiatric symptoms
Description
Change in Neuropsychiatry Inventory (NPI) NPI: Neuropsychiatry Inventory Minimum value: 0 Maximum value: 144 The higher score means a worse outcome
Time Frame
week 0, 8, 16, 24
Title
The improvement of Parkinson's disease
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.
Time Frame
week 0, 8, 16, 24
Title
Behavioral Pathology of dementia
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.
Time Frame
week 0, 8, 16, 24
Title
Severity of dementia
Description
Change in Clinical Dementia Rating (CDR) CDR: Clinical Dementia Rating Minimum value: 0 Maximum value: 5 The higher score means a worse outcome.
Time Frame
week 0, 8, 16, 24
Title
Neuroimaging examinations
Description
Neuroimaging examinations contains: (1) Structural MRI, (2) Resting-state fMRI, and (3) Working memory fMRI.
Time Frame
week 0, 24
Title
Face perception
Description
Changes in perceptual discriminability (d-prime index) Minimum value: 0 (chance level); Maximum value: 3.0 (nearly perfect)
Time Frame
week 0, 8, 16, 24
Title
Emotion recognition and imitation
Description
Changes in emotion recognition accuracy and imitation probability Minimum value: 0%; Maximum value: 100% (Higher score indicate a better outcome)
Time Frame
week 0, 8, 16, 24
Title
Transcranial magnetic stimulation
Description
Change in Transcranial Magnetic Stimulation (TMS) assessments
Time Frame
week 0, 8, 16, 24
Title
Electroencephalography
Description
Changes in Mismatch negativity (MMN)
Time Frame
week 0, 8, 16, 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: PD-D will be diagnosed according to the criteria proposed by Movement Disorder Society task force statement. (Emre et al. 2007) . The following wordings are modified from the task force statement. I. Core features Diagnosis of PD according to Queen Square Brain Bank criteria A dementia syndrome with insidious onset and slow progression, developing within the context of established PD and diagnosed by history, clinical, and mental examination, defined as: Impairment in more than one cognitive domain Representing a decline from premorbid level Deficits severe enough to impair daily life, independent of the impairment ascribable to motor or autonomic symptoms MMSE score between 10-26. II. Associated clinical features Cognitive features: Impaired attention, executive functions, visuo-spatial functions or memory. Core functions of language are largely preserved. Behavioral features: Apathy Changes in personality and mood Hallucination• Delusions Excessive daytime sleepiness III. Features which do not exclude PD-D, but make the diagnosis uncertain Co-existence of any other abnormality which may by itself cause cognitive impairment, but judged not to be the cause of dementia. Time interval between the development of motor and cognitive symptoms is uncertain IV. Features suggesting other conditions or diseases as cause of mental impairment, which, when present make it impossible to reliably diagnose PD-D Cognitive and behavioral symptoms appearing solely in the context of other conditions such as: Acute confusion due to systemic illnesses or drug intoxication. Major depression Features compatible with "Probable Vascular dementia" criteria according to NINDS-AIREN Criteria for the diagnosis of probable and possible PD-D [Probable PD-D] Both core features must be present. In associated clinical features, typical profile of cognitive deficits should be present in at least 2 of the 4 core cognitive domains. The presence of at least one behavioral symptom supports the diagnosis of probable PD-D. None of group III and IV features is present. [Possible PD-D] Both core features must be present. In associated clinical features, the cognitive impairment is atypical in one or more domains. The behavioral symptoms are not necessary to be present. One or more of the group III features may be present. No group IV feature is allowed to be present. Exclusion Criteria: Patients with uncontrollable malignancy, severe heart failure, uremia under hemodialysis, or decompensated liver cirrhosis. Patients taking anticholinergics within 30 days of recruitment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hsien-Yuan Lane, M.D., Ph.D
Phone
886 921 067260
Email
hylane@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lane
Organizational Affiliation
Department of Psychiatry, China Medical University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Psychiatry, China Medical University Hospital
City
Taichung
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hsien-Yuan Lane, M.D., Ph.D
Phone
886 921 067260
Email
hylane@gmail.com

12. IPD Sharing Statement

Learn more about this trial

Multidisciplinary Study of Novel NMDA Modulation for Neurodegenerative Disorder

We'll reach out to this number within 24 hrs