Testing whether D-serine affects Parkinson’s progression

This clinical study, designed as a randomized, double-blind, placebo-controlled trial, aims to investigate if modulation of the N-methyl-D-aspartate receptor (NMDAR) via its co-agonist D-serine has therapeutic benefits in Parkinson's disease (PD). All patients will receive both placebo and D-serine over different time periods during the study. Preclinical studies have shown that blocking glycine transporters, which elevates endogenous glycine levels, can restore NMDAR function and improve motor deficits in PD models. A clinical trial demonstrated that oral D-serine (30 mg/kg/day for 6 weeks) significantly reduced extrapyramidal and abnormal involuntary movements in PD patients compared to placebo, with improvements observed in both motor and non-motor symptoms. D-serine supplementation has shown an acceptable safety profile with doses up to 120 mg/kg showing no significant adverse effects in clinical studies. The D-SPARK trial primarily aims to determine the efficacy of D-serine supplementation on clinical severity of PD as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Secondary aims are to determine the efficacy of D-serine supplementation on improving dopaminergic nigrostriatal innervation as measured by single-photon emission tomography (SPECT) based imaging of the dopamine transporter (DaT-scan) and cognition as measured by the California Verbal Learning Test version 2 (CLVT-II). The study will include 100 persons with Parkinson's disease (PwPD) diagnosed no longer than 5 years before baseline. Participants will be randomly assigned to receive D-Serine 4000 mg daily or placebo for defined periods of time during a 58 week treatment period, followed by a 12 week washout period. Participants will undergo: * Clinical evaluations, including clinical rating scales and questionnaires. * Cognitive assessments. * Bio sampling of whole blood and blood plasma. * Single-photon emission tomography (SPECT) imaging of dopamine transporter levels (DaT-scan) The outcomes of this study could potentially demonstrate that D-serine reduces symptom severity in Parkinson's disease and/or has an impact on the clinical trajectory of Parkinson's disease, benefiting persons living with Parkinson's disease, their families and society as a whole.

The study design is a randomized, double-blind, placebo-controlled trial. The trial consists of 3 stages followed by a washout period. * Screening and antiparkinsonian treatment optimization: \--- Potential participants will be screened for eligibility and consented for participation. Treatment of Parkinson's disease with dopaminergic drugs will be initiated/adjusted until an optimal, stable effect of treatment is established. This treatment regimen will be maintained throughout the first 32 weeks of the intervention stage, after which changes will be allowed. If an optimal, stable dose is not achieved during screening, these participants will not proceed further and will not be included in the study. * Intervention stage: \--- Participants will undergo randomization and will be assigned to receive either placebo or D-serine during different portions of the intervention phase. Participants will receive study drug (placebo or D-serine) for a total of 58 weeks. Thirty-two weeks after starting study drug, participants may have their dopaminergic drugs adjusted, if necessary. * Washout stage: * Upon completion of the intervention period, participants will discontinue study drug and will be followed for an additional 12 weeks. A final study visit will occur 12 weeks after discontinuation of study drug.