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

China Medical University

Status: Completed

Conditions: Parkinson's Disease With Dementia

Treatments: Dietary Supplement: Sarcosine Capsule; Dietary Supplement: Placebo Capsule

Study type: Interventional

Funder types: Other

Identifiers

NCT01785628

DMR98-IRB-296

Details and patient eligibility

About

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).

Full 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

Enrollment: 30 patients

Sex: All

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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30 participants in 2 patient groups, including a placebo group

Sarcosine capsule

Experimental group

Description:

Oral capsules of Sarcosine (0.5g capsule) 1g / bid for 8 weeks.

Treatment:

Dietary Supplement: Sarcosine Capsule

Placebo capsule

Placebo Comparator group

Description:

Oral capsules of Placebo (Dextrin 0.5g capsule) 1g / bid for 8 weeks.

Treatment:

Dietary Supplement: Placebo Capsule