Low Dose Niacin (Vitamin B3) for Parkinson's Disease

Not Applicable

Terminated

Conditions: Parkinson's Disease

Interventions: Other: Placebo
Dietary Supplement: Niacin
Dietary Supplement: Niacinamide

Registration Number: NCT03808961

Lead Sponsor: VA Office of Research and Development

Brief Summary: (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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 7

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 3 ? Placebo Wait-listed Arm	Placebo	Oral placebo twice daily x 18- months with assessments @ baseline, 6 month, 12 month and 18 months
Group 1 ? Niacin Arm	Niacin	Oral 100 mg fixed dose twice daily x 18-months (200 mg total / day) with assessments @ baseline, 6 month, 12 month and 18 months
Group 2 ? Niacinamide Arm	Niacinamide	Oral 100 mg fixed dose twice daily (200 mg total / day) x 18-months with assessments @ baseline, 6 month, 12 month and 18 months

Primary Outcome Measures

Name	Time	Method
Unified Parkinson's Disease Rating Scale (UPDRS) Change	Baseline, 6 month, 12 month and 18 months	This is the Unified Parkinson's disease rating scale assessment. The investigators assess part III of the UPDRS regarding motor skills. The values reported are the averages of baseline, 6months, 12 months, and 18 months values combined for all the participants in that group. So, in the niacin and the niacinamide groups, it indicated the average of 8 values and in the control group it is the average of 12 values. A score is recorded according to the motor skills recorded ranging from 0-5 in each test, 0 being normal and 5 being affected most. Scores are given judging the motor skills. The score may range between 0-132. Lower scores indicate better outcome.
Mini-Mental State Examination (MMSE) Change	Baseline, 6 month, 12 month and 18 months	It captures mental status and awareness of time, place and surrounding. Score ranges from 0-30, 30 denotes the best score and best mental status. All the values in the group are pooled for an average score at baseline, 6 months, 12 months, and 18 months. Therefore, Niacin and Niacinamide groups each demonstrates average of 8 values while placebo group shows average of 12 values.

Secondary Outcome Measures

Name	Time	Method
Visual Analogue Fatigue Scale Changes	Baseline, 6 month, 12 month and 18 months	Fatigue is self-reported on the Visual analogue fatigue scale (VAFS). Participants were asked about how much fatigue they feel ranging from no fatigue (score 0) to extreme fatigue (score 10). Each participant was asked about this score at baseline, 6 months, 12 months, and 18 months visit. Data reported is the averages of all the scores from that group for all the time points.
Trail Making Test Time Change	Baseline, 6 month, 12 month and 18 months	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. Each A and B demonstrates averages from baseline, 6 months, 12 months and 18 months of all the participants. Therefore, in the niacin group A and group B each show averages of 8 values while the control group shows averages of 12 values.