NAPS: Niacin for Parkinson's Disease

NAPS：烟酸治疗帕金森病

• 批准号: 10291779
• 负责人: Chandramohan Wakade
• 金额: --
• 依托单位: CHARLIE NORWOOD VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10291779
• 关键词: Alzheimer' s Disease; Anti-Inflammatory Agents; Binding; Carbidopa; Cause of Death; Cells; Cessation of life; Chronic; Complex; Craniocerebral Trauma; DNA Repair; Development; Diagnosis; Direct Costs; Disease; Disease Progression; Dopamine; Dose; Double-Blind Method; Drowsiness; Dyskinetic syndrome; Electron Transport; Energy Supply; Energy-Generating Resources; Equilibrium; Facilities and Administrative Costs; Fatigue; Foundations; Glycolysis; Hospital Costs; Individual; Inflammation; Intention; Intervention; Learning; Left; Leukocytes; Measurement; Medical Care Costs; Mitochondria; Moods; Motor; Movement; Movement Disorder Society Unified Parkinson' s Disease Rating Scale; Muscle Cramp; NADH; Neurodegenerative Disorders; Neurologic; Niacinamide; Nicotinic Acids; Operative Surgical Procedures; Outcome; Oxidative Stress; Pain; Parkinson Disease; Pathology; Patients; Pharmaceutical Preparations; Physical Rehabilitation; Placebos; Population; Prospective cohort; Randomized; Receptor Up-Regulation; Reporting; Role; Severities; Sleep Disorders; Source; Substantia nigra structure; Supplementation; Symptoms; Testing; Therapeutic; Time; Tremor; Tryptophan Metabolism Pathway; United States; Up-Regulation; Veterans; Vitamin Deficiency; Wages; War; aging population; arm; cognitive function; common symptom; cost; design; disability; disabling symptom; executive function; experience; macrophage; motor symptom; neuroinflammation; novel; nutritional supplementation; premature; primary endpoint; receptor; secondary endpoint; symptomatic improvement; wearable device

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.

项目总结/摘要 我们是第一组证明慢性维生素B3（烟酸和烟酰胺）缺乏的个人， 帕金森病（PD）。烟酸和烟酰胺是提供能量和DNA的NAD的来源 修复身体的每一个细胞。PD患者经常报告我们认为与PD相关的症状。 维生素缺乏，包括白天疲劳、睡眠功能障碍和情绪低落。 此外，烟酸而不是烟酰胺作用于GPR 109 A，一种抗炎受体。我们也是第一 组显示PD的白色血细胞（巨噬细胞）和黑质中升高的GPR 109 A水平 患者，提供了额外的证据，慢性烟酸缺乏症的后果PD。 在这项探索性试验中，我们建议提供非处方营养补充剂，以测试 通过烟酸的双重作用（能量供应和抗炎）纠正缺乏的假设将 改善症状结果和减轻炎症。 目标1.为了确定烟酸补充剂是否会减少炎症并改善 PD患者症状优于烟酰胺。 目标二。为了确定巨噬细胞极化和线粒体增强是否反映烟酸和 烟酰胺补充独立。 我们将通过一项双臂双盲、随机、固定剂量、平行烟酰胺- 对照意向治疗18个月前后前瞻性队列设计，采用中点评估。 本试验的主要终点将是运动症状严重程度的降低， 统一帕金森病评定量表运动部分（UNITED Parkinson's Disease Rating Scale Motor Section，简称UNITED III）。次要终点包括可穿戴设备- 记录平衡控制和认知功能改善的技术测量，包括 夜间睡眠和执行控制，以及糖酵解增加和GPR 109 A水平降低。