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

Parkinson's Disease With Dementia Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01785628
• Other study ID #: DMR98-IRB-296
• Status: Completed
• Phase: N/A
• First received: June 24, 2011
• Last updated: August 20, 2013
• Start date: August 2010
• Est. completion date: July 2012

Study information

• Verified date: August 2013
• Source: China Medical University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial Summary

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).

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: July 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease With Dementia

Intervention

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 Capsule
Placebo is dextrin composition.

Locations

Country	Name	City	State
Taiwan	China Medical University Hospital/Neuro Depart.	Taichung

Sponsors (2)

Lead Sponsor	Collaborator
China Medical University Hospital	National Science Council, Taiwan

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Brain Imaging by 18F-FDG PET From Baseline to 8 Weeks.	18F-FDG PET scan : 8 patients for treatment and placebo groups,respectively.	baseline to 8 weeks	No
Other	Change in Brain Imaging by [99mTc]TRODAT-1 From Baseline to 8 Weeks.	[99mTc]TRODAT-1 : 7 patients for treatment and placebo groups, respectively.	baseline to 8 weeks	No
Primary	Change in Unified Parkinson's Disease Rating Scale (UPDRS) From 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.	No
Secondary	Change in Cognitive Abilities Screening Instrument (CASI) From 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	No
Secondary	Change in Clinical Dementia Rating (CDR) From 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	No
Secondary	Change in Neuropsychiatry Inventory (NPI) From 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	No
Secondary	Change in Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) From 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	No
Secondary	Change in Hamilton Depression Rating Scale (HAM-D) From 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	No
Secondary	Change in Beck Depression Inventory-II (BDI-II) From 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	No
Secondary	Change in The 39-item Parkinson's Disease Questionnaire (PDQ-39) From 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	No