Clinical trial NCT01785628: The Impact of Pharmacological and Electric Modulation of NMDA Pathway on the Cognitive Flexibility and Volitional Movement Preparation in Patients With Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson's Disease With Dementia
Keywords: Parkinson's disease
dementia
NMDA
event related potential
Bereitschaftspotential
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
Collaborators: name: National Science and Technology Council, Taiwan
First posted: 2013-02-07
Enrollment: 30
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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).

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

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Unified Parkinson's Disease Rating Scale (UPDRS) From Baseline to 8 Weeks.
timeFrame: baseline to 8 weeks.
Secondary outcomes:
measure: Change in Cognitive Abilities Screening Instrument (CASI) From Baseline to 8 Weeks.
timeFrame: baseline to 8 weeks
measure: Change in Clinical Dementia Rating (CDR) From Baseline to 8 Weeks.
timeFrame: baseline to 8 weeks
measure: Change in Neuropsychiatry Inventory (NPI) From Baseline to 8 Weeks.
timeFrame: baseline to 8 weeks
measure: Change in Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) From Baseline to 8 Weeks.
timeFrame: baseline to 8 weeks
measure: Change in Hamilton Depression Rating Scale (HAM-D) From Baseline to 8 Weeks.
timeFrame: baseline to 8 weeks
measure: Change in Beck Depression Inventory-II (BDI-II) From Baseline to 8 Weeks.
timeFrame: baseline to 8 weeks
measure: Change in The 39-item Parkinson's Disease Questionnaire (PDQ-39) From Baseline to 8 Weeks.
timeFrame: baseline to 8 weeks
Other outcomes:
measure: Change in Brain Imaging by 18F-FDG PET From Baseline to 8 Weeks.
timeFrame: baseline to 8 weeks
measure: Change in Brain Imaging by [99mTc]TRODAT-1 From Baseline to 8 Weeks.
timeFrame: baseline to 8 weeks
Locations:
city: Taichung
country: Taiwan
facility: China Medical University Hospital/Neuro Depart.
Study officials:
affiliation: Department of Neurology, China Medical University Hospital, Taichung, Taiwan
name: Chon-Haw Tsai, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tsai CH, Huang HC, Liu BL, Li CI, Lu MK, Chen X, Tsai MC, Yang YW, Lane HY. Activation of N-methyl-D-aspartate receptor glycine site temporally ameliorates neuropsychiatric symptoms of Parkinson's disease with dementia. Psychiatry Clin Neurosci. 2014 Sep;68(9):692-700. doi: 10.1111/pcn.12175. Epub 2014 Apr 14.