NAPS: Niacin for Parkinsons Disease

Sponsor

VA Office of Research and Development (U.S. Fed)

Overall Status

Active, not recruiting

CT.gov ID

NCT03808961

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.1

Patients Per Site Per Month

Study Details

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	N/A

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

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.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 :

Jan 1, 2020

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Apr 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 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

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

Outcome Measures

Primary Outcome Measures

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.
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.
Macrophage and cytokine changes [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.
Niacin changes [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

Visual analogue fatigue scale changes [Baseline, 6 month, 12 month and 18 months]
Fatigue is self-reported on the Visual analogue fatigue scale (VAFS).
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.
Arm strength and fatigue [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

Criteria

Ages Eligible for Study:

35 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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