Clinical trial NCT03808961: Low Dose Niacin (Vitamin B3) for Parkinson's Disease
Official title: NAPS: Niacin for Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Parkinson's Disease
Keywords: Parkinson's disease, Niacin, Niacinamide
Niacin
Niacinamide
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2019-01-18
Enrollment: 7
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: There are three arms, niacin, niacinamide and placebo. They are double blind and randomized.
Primary purpose: HEALTH_SERVICES_RESEARCH

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.

Eligibility 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

Primary outcomes:
measure: Unified Parkinson's Disease Rating Scale (UPDRS) Change
timeFrame: Baseline, 6 month, 12 month and 18 months
measure: Mini-Mental State Examination (MMSE) Change
timeFrame: Baseline, 6 month, 12 month and 18 months
Secondary outcomes:
measure: Visual Analogue Fatigue Scale Changes
timeFrame: Baseline, 6 month, 12 month and 18 months
measure: Trail Making Test Time Change
timeFrame: Baseline, 6 month, 12 month and 18 months
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Charlie Norwood VA Medical Center, Augusta, GA
state: Georgia
Study officials:
affiliation: Charlie Norwood VA Medical Center, Augusta, GA
name: Chandramohan Wakade, MBBS
role: PRINCIPAL_INVESTIGATOR
References: