D-SPARK: A Randomized Double Blind Clinical Trial of D-Serine for Modifying Parkinson’s Disease Progression
D-serine is a promising therapeutic candidate for Parkinson’s disease (PD), targeting NMDA receptor signalling pathways involved in motor function, synaptic plasticity, and neuronal survival. The D-SPARK study was designed to evaluate the efficacy, safety, and tolerability of D-serine as a potential disease-modifying treatment for people with PD.
Disease: Parkinson's disease
Type of study: Interventional trial
Coordinating Investigator: Haakon Berven
Study Director: Charalampos Tzoulis
Background
Increasing evidence supports that modulation of the N-methyl-D-aspartate (NMDA) receptor may have therapeutic benefits in neurodegenerative diseases. D-serine is an amino acid that functions as a full agonist of the glycine site of NMDA receptors, which are important for synaptic plasticity, motor control, and neuronal survival. NMDA receptor-mediated neurotransmission is involved in both motor and non-motor symptoms in PD. Preclinical evidence shows that elevating endogenous glycine levels can improve motor deficits in PD models, and a 6-week crossover trial administering D-serine vs placebo in 10 persons with PD showed improved clinical rating scores with D-serine treatment.
The primary objective of the D-SPARK study is to evaluate the effect of orally administered D-serine, 2 g twice per day, versus placebo on overall symptom severity in Parkinson’s disease.
Design
D-SPARK is a 70-week, randomized, doubleblind, placebo-controlled Phase II study evaluating the efficacy, safety, and tolerability of D-serine in 100 participants with clinically established Parkinson’s disease.
Primary endpoint: Difference between treatment groups (D-Serine vs Placebo) in mean change from baseline to week 26 in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDSUPDRS) Total score (sum of parts I-III).
Status
The trial obtained funding and ethics approval in 2025. It opened for participant recruitment in early January 2026, with the first participant enrolled on the 20th of January 2026.
Participating centres
- Haukeland University Hospital, Bergen, Norway
- University of Oslo, Campus Akershus University Hospital, Norway (Planned)
- Sørlandsklinikken, Arendal, Norway (planned)
Funding
- SPARK NS
- The Regional Health Authority of Western Norway
- Haukeland University Hospital