NCT07312110

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P50-P75 for phase_2

Timeline
32mo left

Started Jan 2026

Typical duration for phase_2

Geographic Reach
1 country

11 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress12%
Jan 2026Dec 2028

First Submitted

Initial submission to the registry

November 21, 2025

Completed
1 month until next milestone

First Posted

Study publicly available on registry

December 31, 2025

Completed
1 day until next milestone

Study Start

First participant enrolled

January 1, 2026

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2028

Expected
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2028

Last Updated

January 6, 2026

Status Verified

January 1, 2026

Enrollment Period

2.2 years

First QC Date

November 21, 2025

Last Update Submit

January 5, 2026

Conditions

Parkinson s DiseaseParkinson Disease (PD)

Keywords

SerineParkinsons diseaseD-serine

Outcome Measures

Primary Outcomes (1)

  • Change in MDS-UPDRS Total Score (sum of Parts I-III).

    Difference between treatment groups (DSR vs placebo) in mean change from baseline to Week 26 in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (sum of Parts I-III), assessed in all randomized participants under a treatment-policy strategy. MDS-UPDRS Part III tested in the OFF-medication state. MDS-UPDRS sum of part I-III: Clinical rating scale of motor and non-motor symptoms of Parkinson's Disease. Part I (13 items; Score 0-52) examines non-motor experiences, Part II (13 items; Score 0-52) examines motor experiences of daily living, Part III (33 items; Score 0-132) examines the cardinal motor disabilities. Each Part has 0-4 ratings, where 0 (no problems) to 4 (severe problems) and scores for each part are summed to calculate the total score which ranges from 0-236. Higher scores represent a worse outcome.

    26 weeks.

Secondary Outcomes (4)

  • Change in mean striatal binding ratio (SBR) of the putamen bilaterally, measured by [¹²³I] FP-CIT Single-Photon Emission Computed Tomography (SPECT) Imaging of the Dopamine Transporter (DaT-scan).

    26 Weeks.

  • Change in MDS-UPDRS part III score.

    26 Weeks.

  • Change in EQ-5D-5L index value.

    26 Weeks.

  • Change in CVLT-II total Score and sub-scores.

    26 Weeks.

Other Outcomes (18)

  • Change in MDS-UPDRS part I score.

    26 Weeks.

  • Change in MDS-UPDRS part II score.

    26 Weeks.

  • Change in MDS-UPDRS part IV score.

    26 Weeks.

  • +15 more other outcomes

Study Arms (2)

Early-start

ACTIVE COMPARATOR

Participants in this group will receive D-serine at an earlier time point than the placebo group. All participants will receive placebo and D-serine at different parts of the study.

Dietary Supplement: D-serineDietary Supplement: Placebo

Delayed-start

PLACEBO COMPARATOR

Participants in this group will receive D-serine at a later time point than the early-start group. All participants will receive placebo and D-serine at different parts of the study

Dietary Supplement: D-serineDietary Supplement: Placebo

Interventions

D-serineDIETARY_SUPPLEMENT

D-serine 2 x 500 mg and 2 x Placebo oral capsules administered twice daily the first week of intervention, then uptitrated to D-serine 4 x 500 mg twice daily for the remainder of the intervention.

Delayed-startEarly-start
PlaceboDIETARY_SUPPLEMENT

Placebo 2 x oral capsules administered twice daily.

Delayed-startEarly-start

Eligibility Criteria

Age40 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • A clinical diagnosis of PD\* according to the clinically established MDS clinical diagnostic criteria for Parkinson's disease within 5 years.
  • \[¹²³I\]FP-CIT single photon emission CT (DaTscan) confirming dopaminergic nigrostriatal denervation.
  • Hoehn and Yahr score \< 3 at enrollment.
  • Optimal symptomatic PD treatment, not requiring adjustments, for at least 2 weeks.
  • Age ≥40 and ≤ 80 years at time of enrollment.

You may not qualify if:

  • Dementia or neurodegenerative disorder other than PD at baseline visit.
  • Atypical parkinsonism (PSP, MSA, CBD vascular parkinsonism, or drug induced parkinsonism).
  • Any known monogenic cause of PD (GBA1 variation is accepted).
  • Any psychiatric disorder that would interfere with compliance in the study.
  • Any severe somatic illness that would make the individual unable to comply and participate in the study.
  • Use of D-serine supplementation within 90 days of enrolment.
  • Metabolic, neoplastic, or other physically or mentally debilitating disorder at baseline visit.
  • Active of planned pregnancy during trial period.
  • Cognitive impairment as measured by the Mini Mental Status Exam MMSE) \< 20.
  • Weight \< 45 kg.
  • Urinary albumin/creatinine ratio ≥ 20 mg/mmol at time of enrollment.
  • Participants will be excluded if they have CKD stage 3 or higher, defined as:
  • Estimated golumerular filtration rate (eGFR) \< 60 mL/min/1.73min\^2 at screening, calculated using the CKD-EPI 2021 creatinine equation.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Sørlandet Hospital Arendal

Arendal, Agder, 4838, Norway

NOT YET RECRUITING

Akershus University Hospital

Lørenskog, Akershus, 1478, Norway

NOT YET RECRUITING

Vestre Viken Hospital

Drammen, Buskerud, 3004, Norway

NOT YET RECRUITING

Molde Hospital

Molde, Møre og Romsdal, 6412, Norway

NOT YET RECRUITING

Bodø Hospital (Nordland Hospital)

Bodø, Nordland, 8006, Norway

NOT YET RECRUITING

Oslo University Hospital

Oslo, Oslo County, 0450, Norway

NOT YET RECRUITING

Haugesund Hospital

Haugesund, Rogaland, 5528, Norway

NOT YET RECRUITING

University Hospital of North Norway

Tromsø, Troms, 9019, Norway

NOT YET RECRUITING

Haukeland University Hospital

Bergen, Vestland, 5021, Norway

RECRUITING

Førde Hospital

Førde, Vestland, 6812, Norway

NOT YET RECRUITING

Østfold Hospital

Sarpsborg, Østfold fylke, 1714, Norway

NOT YET RECRUITING

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian DisordersBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesMovement DisordersSynucleinopathiesNeurodegenerative Diseases

Central Study Contacts

Charalampos Tzoulis, MD, PhD

CONTACT

55975061charalampos.tzoulis@helse-bergen.no

Haakon Berven, MD

CONTACT

55975045haakon.berven@helse-bergen.no

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Masking Details
Double-blinded.
Purpose
TREATMENT
Intervention Model
CROSSOVER
Model Details: All participants will be assigned to placebo and D-serine at different time periods during the course of the study.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 21, 2025

First Posted

December 31, 2025

Study Start

January 1, 2026

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

December 1, 2028

Last Updated

January 6, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will share

Individual participant data in pseudonomized format will be shared with collaborators for analysis based on data tranfer agreements adhering to the Eu's General Data Protection Regulation (GDPR).

Locations

NO(11)