The Impact of Pharmacological and Electric Modulation of NMDA Pathway on the Cognitive Flexibility and Volitional Movement Preparation in Patients With Parkinson's Disease

August 20, 2013 updated by: Chon-Haw Tsai, China Medical University Hospital
The project will investigate the effect of pharmacological and electric modulation of N-methyl-D-aspartate (NMDA) pathway on the cognitive flexibility and volitional movement preparation in patients with Parkinson's disease (PD).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Sarcosine (also called N-methylglycine) is an endogenous GlyT-1 inhibitor. By blocking glycine uptake, sarcosine increases synaptic glycine concentration to enhance NMDA receptor function. NMDA receptor, a subtype of ionotropic glutamate receptors, serves important functions in the brain, including learning, memory, cognition, and neural plasticity under physiological conditions and contributes to neurodegeneration in pathophysiological processes. NMDA receptor represents collectively a group of heteromeric tetramers. Every NMDA receptor is a protein complex, typically composed of two NR1 subunits and two NR2 subunits that together form the NMDA receptor ion channel. It requires two receptor agonists (glutamate for the NR2 binding site and glycine for the NR1 binding site) to open the ion channel for NMDA receptor activation. Clinically, modulation through the NMDA-NR1-glycine site is preferred to avoid the excitotoxicity associated with the glutamate site activation.8 In addition, recent animal studies have shown that dopamine secretion can be enhanced by either blocking the striatal NR2 or by activation of the NMDA-receptor glycine site. In the project, we will focus on pharmacological enhancement of NMDA-glycine receptor function based on increasing synaptic glycine concentration by sarcosine administration to examine whether enhancing NMDA-glycine receptor activity can improve the neuropsychiatric symptoms, cognition and hopefully motor function in PD-D patients

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taichung, Taiwan
        • China Medical University Hospital/Neuro Depart.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • The diagnosis of PD-D will be based on the criteria proposed by 2007 movement disorders PD-D task force. (Emre M et.al. Mov Disord 2007; 22:1689-1707)

Exclusion Criteria:

  • Acute confusion due to systemic illnesses or drug intoxication.
  • Major depression
  • Features compatible with "Probable Vascular dementia.
  • Patient who is pregnant.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sarcosine capsule
Oral capsules of Sarcosine (0.5g capsule) 1g / bid for 8 weeks.
Dietary supplement: Sarcosine Capsule
Sarcosine is a glycine transporter-1 (GlyT-1) inhibitor. By blocking glycine uptake, sarcosine increases synaptic glycine concentration to enhance NMDA receptor function.
Placebo Comparator: Placebo capsule
Oral capsules of Placebo (Dextrin 0.5g capsule) 1g / bid for 8 weeks.
Dietary supplement: Placebo Capsule
Placebo is dextrin composition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Unified Parkinson's Disease Rating Scale (UPDRS) From Baseline to 8 Weeks.
Time Frame: baseline to 8 weeks.
Outcome is defined as change in total Unified Parkinson's Disease Rating Scale (UPDRS) between the baseline to 8 weeks. The UPDRS score has three parts, part I (Mentation, Behavior and Mood), Part II (Activities of Daily Living) and Part III (Motor Examination). Each consisting of questions answered on a 0-4 point scale. The minimum total score possible is 0 and the maximum total score possible is 176. Higher scores indicating more severe symptoms.
baseline to 8 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Cognitive Abilities Screening Instrument (CASI) From Baseline to 8 Weeks.
Time Frame: baseline to 8 weeks
The Cognitive Abilities Screening Instrument (CASI) has a score range of 0 to 100 and provides quantitative assessment on attention, concentration, orientation, short-term memory, long-term memory, language abilities, visual construction, list-generating fluency, abstraction, and judgment. With a higher score indicating Symptom improvement.
baseline to 8 weeks
Change in Clinical Dementia Rating (CDR) From Baseline to 8 Weeks.
Time Frame: baseline to 8 weeks
The CDR is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to Alzheimer disease and related dementias: Memory, Orientation, Judgment & Problem Solving, Community Affairs, Home & Hobbies, and Personal Care. With a higher score indicating more severe symptoms.
baseline to 8 weeks
Change in Neuropsychiatry Inventory (NPI) From Baseline to 8 Weeks.
Time Frame: baseline to 8 weeks
The NPI scale has 12 domains: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, night-time behavior disturbances, and appetite and eating abnormalities. The total score ranges from 0 to 144, where the score for a domain is defined as the product of frequency (range: 1-4) and severity (range: 1-3). Each domain has a maximum score of 12 and with a higher score indicating more severe symptoms.
baseline to 8 weeks
Change in Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) From Baseline to 8 Weeks.
Time Frame: baseline to 8 weeks
The Behave-AD includes the assessment of symptoms and a global rating of caregiver distress. A total of 25 symptoms in 7 clusters are rated: paranoid and delusional ideation, hallucinations, aggressiveness, activity disturbances, diurnal rhythm disturbances, affective disturbances and anxieties, and phobias. Caregivers rate behavioral symptoms over the preceding 2 weeks on a 0 to 3 scale. The caregiver also determines a global assessment of caregiver distress on a scale of 0 to 3. The maximum score is 75 and with a higher score indicating more severe symptoms.
baseline to 8 weeks
Change in Hamilton Depression Rating Scale (HAM-D) From Baseline to 8 Weeks.
Time Frame: baseline to 8 weeks
The HAM-D is a 21-item rating scaled which includes an emphasis on behavioral symptoms and somatic complaints that neglects self-reported feelings of distress; and an intermingling of frequency and intensity of symptoms. The total score ranges from 0 to 64: ten items are ranked on a scale from 0 to 4; 9 items are ranked 0 to 2; and 2 items are ranked 0 to 3. With a higher score indicating more severe symptoms.
baseline to 8 weeks
Change in Beck Depression Inventory-II (BDI-II) From Baseline to 8 Weeks.
Time Frame: baseline to 8 weeks
The BDI-II is a 21-item self-report questionnaire assessing the current severity of depression symptoms. Each item is scored on a scale of 0 to 3 and the total score ranges from 0 to 63. With a higher score indicating more severe symptoms.
baseline to 8 weeks
Change in The 39-item Parkinson's Disease Questionnaire (PDQ-39) From Baseline to 8 Weeks.
Time Frame: baseline to 8 weeks
The PDQ-39 contains 39-items covering 8 discrete dimensions: mobility, activities of daily living, emotional well-being, stigma, social support, cognitions, communication, and bodily discomfort. Each question is scored on a 5-point scale and recoded to 0 to 4 for the analysis. The total score can range from 0 to 132 and with a higher score indicating more severe symptoms.
baseline to 8 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Brain Imaging by 18F-FDG PET From Baseline to 8 Weeks.
Time Frame: baseline to 8 weeks
18F-FDG PET scan : 8 patients for treatment and placebo groups,respectively.
baseline to 8 weeks
Change in Brain Imaging by [99mTc]TRODAT-1 From Baseline to 8 Weeks.
Time Frame: baseline to 8 weeks
[99mTc]TRODAT-1 : 7 patients for treatment and placebo groups, respectively.
baseline to 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

China Medical University Hospital

Collaborators

National Science Council, Taiwan

Investigators

  • Principal Investigator: Chon-Haw Tsai, MD, PHD, Department of Neurology, China Medical University Hospital, Taichung, Taiwan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2010

Primary Completion (Actual)

June 1, 2012

Study Completion (Actual)

July 1, 2012

Study Registration Dates

First Submitted

June 24, 2011

First Submitted That Met QC Criteria

February 6, 2013

First Posted (Estimate)

February 7, 2013

Study Record Updates

Last Update Posted (Estimate)

August 22, 2013

Last Update Submitted That Met QC Criteria

August 20, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DMR98-IRB-296

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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