D-SPARK: D‑Serine to modify Parkinson's progression

D-SPARK: A Randomized Double Blind Clinical Trial of D-Serine for Modifying Parkinson's Disease Progression

This trial will test whether taking D‑serine can slow Parkinson's progression in people diagnosed within five years.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 40 Years to 80 Years
• Sex: All
• Sponsor: Haukeland University Hospital (Academic / other)
• Locations: 11 sites (Arendal, Agder and 10 other locations)
• Trial ID: NCT07312110 on ClinicalTrials.gov

What this trial studies

D‑SPARK is a randomized, double‑blind, placebo‑controlled Phase 2 trial in which participants receive both oral D‑serine and placebo during different parts of a 58‑week intervention period followed by a 12‑week washout. The protocol includes an initial screening and optimization of dopaminergic therapy to a stable dose before randomization, with medication adjustments allowed after 32 weeks on study drug. Efficacy signals will be compared between D‑serine and placebo treatment periods, and safety will be monitored throughout. The trial requires DaTscan confirmation of nigrostriatal denervation and enrolls people with early PD (Hoehn and Yahr <3).

Who should consider this trial

Good fit: Adults aged 40–80 with clinically established Parkinson's disease within five years, DaTscan‑confirmed dopaminergic denervation, Hoehn and Yahr stage under 3, and on a stable optimal dopaminergic regimen are ideal candidates.

Not a fit: People with dementia, atypical parkinsonism, known monogenic causes of PD (except GBA1), recent D‑serine use, or severe comorbidities that limit participation are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, D‑serine could reduce motor and non‑motor symptom progression and improve daily function in early Parkinson's disease.

How similar studies have performed: Preclinical models and at least one small clinical report showed symptomatic improvement with oral D‑serine, but longer‑term, disease‑modifying evidence in PD remains limited.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Where this trial is running

Arendal, Agder and 10 other locations

• Sørlandet Hospital Arendal — Arendal, Agder, Norway (Not_yet_recruiting)
• Akershus University Hospital — Lørenskog, Akershus, Norway (Not_yet_recruiting)
• Vestre Viken Hospital — Drammen, Buskerud, Norway (Not_yet_recruiting)
• Molde Hospital — Molde, Møre og Romsdal, Norway (Not_yet_recruiting)
• Bodø Hospital (Nordland Hospital) — Bodø, Nordland, Norway (Not_yet_recruiting)
• Oslo University Hospital — Oslo, Oslo, Norway (Not_yet_recruiting)
• Haugesund Hospital — Haugesund, Rogaland, Norway (Not_yet_recruiting)
• University Hospital of North Norway — Tromsø, Troms, Norway (Not_yet_recruiting)
• Haukeland University Hospital — Bergen, Vestland, Norway (Recruiting)
• Førde Hospital — Førde, Vestland, Norway (Not_yet_recruiting)
• Østfold Hospital — Sarpsborg, Østfold fylke, Norway (Not_yet_recruiting)

Study contacts

• Study coordinator: Charalampos Tzoulis, MD, PhD

Conditions Parkinson s Disease; Parkinson Disease; Serine; Parkinsons disease; D-serine