Niacin for Parkinsons Disease (NAPS)

• ClinicalTrials.gov Identifier: NCT03808961
• Recruitment Status: Active, not recruiting
• First Posted: January 18, 2019
• Last Update Posted: March 24, 2022
• Sponsor: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Parkinson's Disease	Dietary Supplement: Niacin; Dietary Supplement: Niacinamide; Other: Placebo	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: There are three arms, niacin, niacinamide and placebo. They are double blind and randomized.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Only Pharmacists keep the log of the drug dispensed. Everyone else is blinded.
• Primary Purpose: Health Services Research
• Official Title: NAPS: Niacin for Parkinsons Disease
• Actual Study Start Date: January 1, 2020
• Estimated Primary Completion Date: November 1, 2023
• Estimated Study Completion Date: April 1, 2024

Arms and Interventions

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 Name: 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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. Unified Parkinson's Disease Rating Scale (UPDRS) change [ Time Frame: 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.
2. Mini-Mental State Examination (MMSE) change [ Time Frame: Baseline, 6 month, 12 month and 18 months ]
   It captures mental status and awareness of time, place and surrounding.
3. Macrophage and cytokine changes [ Time Frame: Baseline, 6 month, 12 month and 18 months ]
   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.
4. Niacin changes [ Time Frame: Baseline, 6 month, 12 month and 18 months ]
   Plasma and urine samples will be tested to report levels of niacin and its metabolites.

Secondary Outcome Measures :

1. Visual analogue fatigue scale changes [ Time Frame: Baseline, 6 month, 12 month and 18 months ]
   Fatigue is self-reported on the Visual analogue fatigue scale (VAFS).
2. Trail making test time change [ Time Frame: 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.
3. Arm strength and fatigue [ Time Frame: Baseline, 6 month, 12 month and 18 months ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Georgia

Charlie Norwood VA Medical Center, Augusta, GA

Augusta, Georgia, United States, 30904

Sponsors and Collaborators

VA Office of Research and Development

Investigators

• Principal Investigator: Chandramohan Wakade, MBBS; Charlie Norwood VA Medical Center, Augusta, GA

More Information

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT03808961
• Other Study ID Numbers: NURE-013-18S
• First Posted: January 18, 2019
• Last Update Posted: March 24, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: At the investigators request, we will share the data
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: One year after the study is closed.
• Access Criteria: When we are ready to publish, the data will be available

• 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

Keywords provided by VA Office of Research and Development:

Parkinson's disease, Niacin, Niacinamide; Niacin; Niacinamide

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Vitamins; Niacin; Niacinamide; Nicotinic Acids; Vitamin B Complex; Micronutrients; Physiological Effects of Drugs; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Vasodilator Agents