D-SPARK: A Randomized Double Blind Clinical Trial of D-Serine for Modifying Parkinson's Disease Progression
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 11
- 主要终点
- Change in MDS-UPDRS Total Score (sum of Parts I-III).
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double-blinded.
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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) <
- •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.
研究组 & 干预措施
Early-start
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.
干预措施: Placebo (Dietary Supplement)
Delayed-start
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
干预措施: Placebo (Dietary Supplement)
Early-start
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.
干预措施: D-serine (Dietary Supplement)
Delayed-start
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
干预措施: D-serine (Dietary Supplement)
结局指标
主要结局
Change in MDS-UPDRS Total Score (sum of Parts I-III).
时间窗: 26 weeks.
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.
次要结局
- 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.)