NR-SAFE: a Safety Study Investigating Treatment With High-dose Nicotinamide Riboside (NR) in Parkinson's Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Incidence of treatment-associated moderate and severe adverse events (AEs).
研究概览
简要总结
NR-SAFE is a double-blinded randomized safety study aiming to determine the safety and tolerability of nicotinamide riboside (NR) at a daily dose of 3000mg, in individuals with Parkinson's disease (PD).
The investigators recently reported the results of the NADPARK study (ClinicalTrials.gov: NCT03816020), a phase I randomized, double-blinded trial, assessing the tolerability, cerebral bioavailability and molecular effects of NR therapy, 1000mg daily, in PD. The NADPARK study showed that NR 1000mg daily was well tolerated and led to a significant, but variable, increase in cerebral NAD levels (measured by 31phosphorous magnetic resonance spectroscopy, 31P-MRS) and related metabolites in the cerebrospinal fluid (CSF). NR recipients showing increased brain NAD levels exhibited altered cerebral metabolism, measured by 18fluoro-deoxyglucose positron emission tomography (FDG-PET), and this was associated with mild clinical improvement. The results of the NADPARK trial nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials.
It is plausible that any beneficial effects of NR in PD may be dose-dependent and more pronounced at higher doses. NR doses of up to 2000mg daily have been tested in healthy humans with no signs of toxicity. However, the safety and tolerability of even higher doses is untested. To enable clinical studies assessing higher doses, the investigators will assess the safety and tolerability of an oral dose of 3000 mg NR daily.
NR-SAFE will recruit 20 participants with PD and randomize them 1:1 to either NR 3000mg daily or placebo for a total duration of 4 weeks.
详细描述
NR-SAFE is a double-blinded randomized safety study aiming to determine the safety and tolerability of nicotinamide riboside (NR) at a daily dose of 3000mg, in individuals with Parkinson's disease (PD). Individuals with PD (n = 20) will be recruited starting April 2022. Participants will be randomized 1:1 to either NR 3000mg daily (1500mg x 2) or placebo per os for a total duration of 4 week. Both the participants and the investigators will be blinded.
Primary Objective:
To determine the safety of oral NR 3000mg daily for a period of 4 weeks in individuals with Parkinson's disease (PD). Safety is defined as the absence of clinically significant NR-associated moderate or severe adverse events (AE).
Secondary Objectives:
- Determine whether oral NR 3000 mg daily is associated with mild AE.
- Assess the effects of oral NR 3000 mg daily on the NAD metabolome in blood and urine.
- Assess the effects of oral NR 3000 mg daily on clinical severity of PD, measured by UPDRS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Both participants and all investigators are blinded during the trial and during data analysis.
入排标准
- 年龄范围
- 35 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age equal to or greater than 35 years and lower than 100 years at time of enrollment.
- •Clinical diagnosis of idiopathic PD according to the MDS criteria.
- •Hoehn and Yahr score < 4 at enrolment.
排除标准
- •Dementia or other neurodegenerative disorder at baseline visit.
- •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 high dose vitamin B3 supplementation within 30 days of enrollment.
- •Metabolic, neoplastic, or other physically or mentally debilitating disorder at baseline visit.
结局指标
主要结局
Incidence of treatment-associated moderate and severe adverse events (AEs).
时间窗: 4 weeks.
The incidence of treatment-associated moderate and severe adverse events (AEs) will be assessed.
次要结局
- Between-group (NR vs placebo) difference in change of clinical severity of PD, measured by UPDRS.(4 weeks.)
- Incidence of treatment-associated mild adverse events (AEs).(4 weeks.)
- Between-group (NR vs placebo) difference in changes of the NAD metabolome in blood and urine, measured by mass spectrometry (LC-MS/MS Q-Exactive HF)(4 weeks.)