GPR109A and Parkinson's Disease: Role of Niacin in Outcome Measures
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 2
- 主要终点
- Unified Parkinson's Disease Rating Scale (UPDRS) Change
研究概览
简要总结
Inflammation plays a central role in Parkinson's disease. The use of anti-inflammatory drugs was found to reduce the risk of PD . Niacin may play an important role in reducing inflammation in PD. The investigators also found that individuals with PD have a chronic niacin deficiency .
The purposes of this study are to (1) examine the blood, urine and spinal fluid of persons with Parkinson's to look for evidence of inflammation and; (2) whether 6 months of vitamin B3 supplements may reduce the inflammation and/or improve symptoms.
详细描述
Inflammation plays a central role in Parkinson's disease (PD) pathology [1] as evidenced by the presence of microglia in the substantia nigra in post-mortem samples [2] as well as activated microglia and cytokines in clinical and animal studies [3]. The use of non-aspirin non-steroidal anti-inflammatory drugs was found to reduce the risk of PD [4]. The investigators recently identified an anti-inflammatory receptor GPR109A that is upregulated in PD [5]. Niacin has a high affinity for this receptor, suggesting that it (niacin) may play an important role in reducing inflammation in PD. The investigators also found that individuals with PD have a chronic niacin deficiency [5]. Using seed funding from the local PD chapter, the investigators obtained pilot data which suggested that restoring the deficiency via over-the-counter (OTC) supplementation reduced inflammation and decreased the severity of the disease symptoms [6]. In this VA-funded study, the investigators will determine the effect of 6 months' OTC niacin supplementation on inflammation (as assessed in the blood and spinal fluid) and severity of the PD symptoms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Health Services Research
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Only Pharmacists keep the log of the drug dispensed. Everyone else is blinded.
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
- •PD subjects will be adult men and women diagnosed with idiopathic mild to moderately severe PD defined as modified Hoehn & Yahr Stages I-III (while "On").
- •PD is defined according to the United Kingdom Brain Bank Criteria made at least six months prior to recruitment to the study.
- •PD features include the presence of at least two of the four cardinal clinical manifestations of the disease, which are tremor, rigidity, bradykinesia, and disturbances of posture or gait, without any other known or suspected cause of Parkinsonism.
- •Subjects should be stabilized on PD medication for at least 3 months before enrollment into the study.
- •Subjects' PD drug prescriptions will not be altered nor withheld during the study, i.e., they will be tested while "On."
- •The patient will have signed informed consent.
- •Subjects who do not have PD (i.e., healthy or have other medical conditions such as traumatic brain injury (TBI), stroke, or other syndromes in which inflammation plays a role in the condition) will also be recruited as control subjects.
- •This will allow us to estimate whether these other conditions show similar or unique inflammatory profile.
排除标准
- •Subjects will be excluded if they had previous brain surgery or other severe neurological problems
- •intracerebral hemorrhage
- •traumatic brain injury
- •central nervous system malignancy
- •active central nervous system (CNS) infection
- •significant stroke
- •Alzheimer disease or any type of implanted stimulator including but not limited to Deep Brain Stimulator (DBS) or pacemaker
- •All subjects must be without evidence of dementia, defined as a score > 24 the Mini-Mental State Examination and able to understand test instructions
- •Subjects must not have functional blindness (inability to participate in gait and visuomotor assessments) or lower limb amputation higher than the forefoot or any orthopedic problem that precludes performance of physical tests
- •Allergic to niacin
- •Significant cardiac, pulmonary, hepatic, gastrointestinal, or renal disease
- •e.g., New York Heart Association Class III or IV congestive heart failure
- •endocarditis
- •pulmonary insufficiency symptomatic at rest or with mild physical exertion
- •acute or chronic hepatitis
- •renal failure requiring dialysis
- •second and third degree atrioventricular block or sick sinus syndrome), or diabetes are also exclusionary factors
结局指标
主要结局
Unified Parkinson's Disease Rating Scale (UPDRS) Change
时间窗: at the recruitment and after 6 months
This is the Unified Parkinson's disease rating scale assessment. The investigators assess I, II, III and V components of the UPDRS. UPDRS 3 is motor skills. Higher scores mean worse outcome. A 0 is minimum and 120 is the maximum.
REM Sleep Pattern
时间窗: baseline and after 6 months
This requires an instrument Zeo sleep monitor. Subjects are given instructions how to use it. Sleep sensor patches are supposed to be applied on forehead before going to sleep and the data of quality of sleep is captured overnight. The reported data captures the rapid eye movement (REM) sleep as a percentage.
Deep Sleep
时间窗: At baseline and after 6 months
This requires an instrument Zeo sleep monitor. Subjects are given instructions how to use it. Sleep sensor patches are supposed to be applied on forehead before going to sleep and the data of quality of sleep is captured overnight. The reported data captures the deep sleep percentage.
Light Sleep
时间窗: baseline and 6 months
This requires an instrument Zeo sleep monitor. Subjects are given instructions how to use it. Sleep sensor patches are supposed to be applied on forehead before going to sleep and the data of quality of sleep is captured overnight. The reported data captures the light sleep percentage.
Sleep Time - Awake
时间窗: at baseline and 6 months
This requires an instrument Zeo sleep monitor. Subjects are given instructions how to use it. Sleep sensor patches are supposed to be applied on forehead before going to sleep and the data of quality of sleep is captured overnight. The reported data captures the awake time during night sleep percentage.
Mini-Mental State Examination (MMSE) Change
时间窗: at baseline and after 6 months of treatment
It captures mental status and awareness of time, place and surrounding. A zero is minimum and 30 is maximum. Higher score indicates better cognition.
Stroop Test Change
时间窗: at the baseline and after 6 months of intervention
It captures understanding of color and its description within a certain time frame when letters and colors do not match. There are only two choices to pick from and the correct choices should be made to proceed to the next one. Correct choices are given one point and incorrect choices delete one point. Maximum number of correct choices per unit time are recorded. Three initial trials are given to understand the test. No minimum or maximum values. Higher numbers indicate better cognition.
Fatigue Severity Scale
时间窗: at baseline and after 6 months
Fatigue was rated from 0-7 in a fatigue questionnaire. A 0 being the least and 7 being the highest level of fatigue.
次要结局
- Niacin Metabolites in Urine - NAM Nicotinamide(at baseline and 6 months)
- Cerebrospinal Fluid Changes - Interleukin 6 (IL6)(at baseline and after 6 months)
- Cerebrospinal Fluid Changes - Interleukin 10 (IL-10)(at baseline and after 6 months)
- Niacin Metabolite in Urine - Niacin(at baseline and after 6 months)
- Niacin Changes in Plasma - Niacin(baseline and 6 months)
- Niacin Changes in Plasma - NUA Nicotinuric Acid(at baseline and 6 months)
- Cerebrospinal Fluid Changes - Interleukin 8 (IL8)(at baseline and after 6 months)
- Niacin Metabolite in Urine - Nicotinuric Acid NUA(at baseline and after 6 months)
- CSF Fluid Changes - Interleukin 1B (IL-1B)(at baseline and 6 months)
- Cerebrospinal Fluid (CSF) Changes - Macrophage Inflammatory Protein 1 Beta (MIP 1 Beta)(at baseline and after 6 months)
- Macrophage Changes(at baseline and after 6 months)
- Niacin Metabolite Changes in Plasma - Nicotinamide (NAM)(at baseline and after 6 months)
- CSF Changes in Interferon Gamma (IF-gamma)(at baseline and after 6 months)
- CSF Changes - Tumor Necrosis Factor - Alpha (TNF-alpha)(at baseline and after 6 months)
- Cerebral Spinal Fluid Changes - Interferon Gamma Induced Protein -10 (IP-10)(at baseline and after 6 months)
- Cerebral Spinal Fluid (CSF) Changes - Monocyte Chemoattractant Protein 4 (MCP4)(at baseline and after 6 months)
- Cerebral Spinal Fluid (CSF) Changes - MIP1-alpha(at baseline and after 6 months)
- Plasma Cytokines - IF Gamma(at baseline and after 6 months)
- Plasma Cytokines - IL-10(at baseline and after 6 months)
- Plasma Cytokines - IL1-B(at baseline and after 6 months)
- Plasma Cytokines - IL-8(at baseline and after 6 Months)
- Plasma Cytokines - TNF-alpha(at baseline and after 6 months)
- Plasma Cytokines - IP-10(at baseline and after 6 months)
- Plasma Cytokines - MCP-4(at baseline and after 6 months)
- Plasma Cytokines - MIP1-alpha(at baseline and after 6 months)
- Plasma Cytokines - MIP1-beta(at baseline and after 6 months)
- Plasma Levels - Serotonin(at baseline and after 6 months)
- Plasma Cytokines - IL-6(at baseline and after 6 months)