NAPS: Niacin for Parkinson's Disease

项目摘要/摘要 我们是第一个发现慢性维生素B3(烟酸和烟酰胺)缺乏的小组。 帕金森氏病(PD)。烟酸和烟酰胺是NAD的来源，NAD提供能量和DNA 修复到体内的每一个细胞。帕金森病患者经常报告的症状，我们认为与 维生素缺乏，包括白天疲劳、睡眠障碍和情绪低落。 此外，作用于抗炎受体Gpr109a的是烟酸，而不是烟酰胺。我们也是第一个 帕金森病患者白细胞(巨噬细胞)和黑质中Gpr109a水平升高 为帕金森病患者慢性烟酸缺乏的后果提供了额外的证据。 在这项探索性试验中，我们建议提供非处方营养补充剂来测试 假设通过烟酸的双重作用(能量供应和抗炎)来纠正虚弱 改善症状和减轻炎症的效果优于烟酰胺。 目的1.确定补充烟酸是否能减轻炎症并改善 帕金森病患者的症状优于烟酰胺。 目的2.确定巨噬细胞极化和线粒体增强是否会反映烟酸和 独立服用烟酰胺补充剂。 我们将通过双臂双盲、随机、固定剂量、平行的烟酰胺来实现这些目标- 受控意向治疗前18个月前瞻性队列设计，中点评估。 这项试验的主要终点将是运动症状严重程度的降低，由 帕金森病统一评定量表运动组(UPDRS III)。次要终端包括可穿戴式- 记录平衡控制和认知功能改进的技术措施包括 夜间睡眠和执行控制，以及糖酵解增加和Gpr109a水平下降。

PROJECT SUMMARY/ABSTRACT We are the first group to demonstrate chronic vitamin B3 (niacin and niacinamide) deficiency in individuals with Parkinson's disease (PD). Niacin and niacinamide are the source of NAD which supplies energy and DNA repair to every cell in the body. PD patients frequently report symptoms which we believe are related to the vitamin deficiency, including daytime fatigue, sleep dysfunction and low-level mood. In addition, niacin but not niacinamide acts on GPR109A, an anti-inflammatory receptor. We are also the first group to show elevated GPR109A levels in the white blood cells (macrophages) and substantia nigra of PD patients, providing additional evidence of the consequences of chronic niacin deficiency in PD. In this exploratory trial, we propose to provide over-the-counter nutritional supplementation to test the hypothesis that correcting the deficiency via niacin's dual actions (energy supply and anti-inflammation) will improve symptom outcomes and reduce inflammation better than niacinamide. Aim 1. To determine whether niacin supplementation will reduce inflammation and improve the symptoms of PD patients better than niacinamide. Aim 2. To determine whether macrophage polarization and mitochondrial boost will reflect niacin and niacinamide supplementation independently. We will accomplish these aims with a two-arm double blind, randomized, fixed-dose, parallel niacinamide- controlled intention-to-treat 18-month pre-post prospective cohort design with mid-point assessment. The primary endpoint of this trial will be a decrease in the severity of motor symptoms as assessed by the Unified Parkinson's Disease Rating Scale Motor Section (UPDRS III). Secondary endpoints include wearable- technology measurements to document improvements in balance control and cognitive functions including nightsleep and executive control, as well as increased glycolysis and decreased GPR109A levels.