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

NAPS: Niacin for Parkinson's Disease

(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.

Study Overview

• Status: Terminated
• Conditions: Parkinson's Disease
• Intervention / Treatment: Dietary supplement: Niacin; Dietary supplement: Niacinamide; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30904-6258
      • Charlie Norwood VA Medical Center, Augusta, GA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1 - Niacin Arm; 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; 100mg tablets twice daily; Other Names: Vitamin B3, Nicotinic acid
Active Comparator: Group 2 - Niacinamide Arm; 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; 100mg tablets twice daily; Other Names: Vitamin B3, Nicotinamide
Placebo Comparator: Group 3 - Placebo Wait-listed Arm; Oral placebo twice daily x 18- months with assessments @ baseline, 6 month, 12 month and 18 months	Other: Placebo; Placebo tablet twice daily

What is the study measuring?

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. 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.	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. 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.	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). 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.	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. 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.	Baseline, 6 month, 12 month and 18 months

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Chandramohan Wakade, MBBS, Charlie Norwood VA Medical Center, Augusta, GA

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Actual): November 1, 2023
• Study Completion (Actual): November 1, 2023

Study Registration Dates

• First Submitted: January 16, 2019
• First Submitted That Met QC Criteria: January 16, 2019
• First Posted (Actual): January 18, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 10, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Niacinamide; Niacin; Parkinson's disease, Niacin, Niacinamide
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Micronutrients; Vasodilator Agents; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Niacin; Niacinamide; Nicotinic Acids; Vitamin B Complex
• Other Study ID Numbers: NURE-013-18S

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: At the investigators request, we will share the data
• IPD Sharing Time Frame: One year after the study is closed.
• IPD Sharing Access Criteria: When we are ready to publish, the data will be available
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No