Niacin for Parkinsons Disease

Study Overview
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Brief Summary
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(1) To examine the blood, urine and spinal fluid of persons with Parkinson's to look for evidence of inflammation and; (2) whether 18 months of vitamin B3(niacin or niacinamide) supplementation may reduce the inflammation and/or improve PD motor and non-motor symptoms.

Detailed Description
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Number of people affected by Parkinson's disease is increasing each year. Vitamin B3 (Niacin/Niacinamide) supplement can be used to slow the progression of PD. Inflammation plays a central role in Parkinson's disease (PD) pathology as evidenced by the presence of microglia in the substantia nigra in post-mortem samples as well as activated microglia and cytokines in clinical and animal studies. The use of non-aspirin non-steroidal anti-inflammatory drugs was found to reduce the risk of PD. The investigators recently identified an anti-inflammatory receptor GPR109A that is upregulated in PD. 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. In a three month trial at Augusta University (the investigators' affiliate) the investigators demonstrated that niacin was helpful for PD patients in reducing inflammatory macrophages and boosting the anti-inflammatory macrophages in blood. In this VA-funded study, the investigators will determine the effect of 18 months over-the-counter (OTC) niacin or niacinamide supplementation on inflammation (as assessed in the blood and spinal fluid) and severity of the PD symptoms.

Official Title
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NAPS: Niacin for Parkinsons Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Dietary Supplement: Niacin
* Dietary Supplement: Niacinamide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PD subjects will be adult men and women diagnosed with idiopathic mild to moderately severe PD The majority of PD subjects are expected to be > 60 years old Disease severity is defined as modified Hoehn & Yahr Stages I-IV (while On) PD is defined according to the UK 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 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 The patient will have signed informed consent Exclusion Criteria: Subjects will be excluded if they present with significant cognitive deficits A MMSE score of 25 is considered substantial global cognitive impairment 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 Subjects must not have known allergy to vitamin B3 Significant cardiac, pulmonary, hepatic, gastrointestinal, renal disease, or uncontrolled/advanced diabetes are also exclusionary factors, 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 (AV) block sick sinus syndrome Subjects will be excluded if they are taking B3 but will be included if they are taking B complex that has very low dose B3 (25 mg) which has minimal effects on GPR109A (based on our unpublished observation) Overall, the investigators will exercise clinical judgment to exclude a subject from the study if, in the investigators' opinion, that a patient presents with a set of comorbidities which renders unsuitability for the study

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: There are three arms, niacin, niacinamide and placebo. They are double blind and randomized.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1 ? Niacin Arm<br>Oral 100 mg fixed dose twice daily x 18-months (200 mg total / day) with assessments @ baseline, 6 month, 12 month and 18 months | Dietary Supplement: Niacin<br>* 100mg tablets twice daily<br>* Other names: Vitamin B3, Nicotinic acid;|
| Active Comparator: Group 2 ? Niacinamide Arm<br>Oral 100 mg fixed dose twice daily (200 mg total / day) x 18-months with assessments @ baseline, 6 month, 12 month and 18 months | Dietary Supplement: Niacinamide<br>* 100mg tablets twice daily<br>* Other names: Vitamin B3, Nicotinamide;|
| Placebo Comparator: Group 3 ? Placebo Wait-listed Arm<br>Oral placebo twice daily x 18- months with assessments @ baseline, 6 month, 12 month and 18 months | Other: Placebo<br>* Placebo tablet twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Unified Parkinson's Disease Rating Scale (UPDRS) change | This is the Unified Parkinson's disease rating scale assessment. The investigators assess part III of the UPDRS regarding motor skills. | Baseline, 6 month, 12 month and 18 months | 
| Mini-Mental State Examination (MMSE) change | It captures mental status and awareness of time, place and surrounding. | Baseline, 6 month, 12 month and 18 months | 
| Macrophage and cytokine changes | The blood is tested to report GPR109A levels in macrophages in M1 and M2 populations. Inflammatory and anti-inflammatory cytokine levels are measured in plasma. | Baseline, 6 month, 12 month and 18 months | 
| Niacin changes | Plasma and urine samples will be tested to report levels of niacin and its metabolites. | Baseline, 6 month, 12 month and 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual analogue fatigue scale changes | Fatigue is self-reported on the Visual analogue fatigue scale (VAFS). | Baseline, 6 month, 12 month and 18 months | 
| Trail making test time change | This is a timed test where the patient connects numbers in order for part A. Numbers and letters are connected interchangeably in past B. The time of B minus the time of A gives a measure for set shift change ability which is reduced in Parkinson's patients. | Baseline, 6 month, 12 month and 18 months | 
| Arm strength and fatigue | An electromyogram is performed on each arm of the patient. The test is recorded and aims to measure muscle strength and fatigue. Patients squeeze a bulb as hard as possible, then hold it for 30 seconds. This is done three times for each hand. | Baseline, 6 month, 12 month and 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Niacin, Niacinamide, Niacin, Niacinamide