GPR109A and Parkinson's Disease: Role of Niacin in Outcome Measures

VA Office of Research and Development47 enrolled

Overview

Inflammation plays a central role in Parkinson's disease. The use of anti-inflammatory drugs was found to reduce the risk of PD . Niacin may play an important role in reducing inflammation in PD. The investigators also found that individuals with PD have a chronic niacin deficiency . The purposes of this study are to (1) examine the blood, urine and spinal fluid of persons with Parkinson's to look for evidence of inflammation and; (2) whether 6 months of vitamin B3 supplements may reduce the inflammation and/or improve symptoms.

Inflammation plays a central role in Parkinson's disease (PD) pathology \[1\] as evidenced by the presence of microglia in the substantia nigra in post-mortem samples \[2\] as well as activated microglia and cytokines in clinical and animal studies \[3\]. The use of non-aspirin non-steroidal anti-inflammatory drugs was found to reduce the risk of PD \[4\]. The investigators recently identified an anti-inflammatory receptor GPR109A that is upregulated in PD \[5\]. 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 \[5\]. Using seed funding from the local PD chapter, the investigators obtained pilot data which suggested that restoring the deficiency via over-the-counter (OTC) supplementation reduced inflammation and decreased the severity of the disease symptoms \[6\]. In this VA-funded study, the investigators will determine the effect of 6 months' OTC niacin supplementation on inflammation (as assessed in the blood and spinal fluid) and severity of the PD symptoms.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

HEALTH_SERVICES_RESEARCH

Masking

QUADRUPLE

Enrollment

Conditions

Parkinson's Disease

Interventions

niacinDIETARY_SUPPLEMENT

Niacin or nicotinic acid 250 mg tablets

placeboOTHER

placebo tablet

Eligibility

Sex: ALLMin age: 35 Years

Medical Language ↔ Plain English

Inclusion Criteria: * PD subjects will be adult men and women diagnosed with idiopathic mild to moderately severe PD defined as modified Hoehn \& Yahr Stages I-III (while "On"). * PD is defined according to the United Kingdom 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, and 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, i.e., they will be tested while "On." * The patient will have signed informed consent. * Subjects who do not have PD (i.e., healthy or have other medical conditions such as traumatic brain injury (TBI), stroke, or other syndromes in which inflammation plays a role in the condition) will also be recruited as control subjects. * This will allow us to estimate whether these other conditions show similar or unique inflammatory profile. Exclusion Criteria: * 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 * Allergic to niacin * Significant cardiac, pulmonary, hepatic, gastrointestinal, or renal disease * 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 block or sick sinus syndrome), or diabetes are also exclusionary factors

Locations (1)

Charlie Norwood VA Medical Center, Augusta, GA

Augusta, Georgia, United States

Outcomes

Primary Outcomes

Unified Parkinson's Disease Rating Scale (UPDRS) Change

This is the Unified Parkinson's disease rating scale assessment. The investigators assess I, II, III and V components of the UPDRS. UPDRS 3 is motor skills. Higher scores mean worse outcome. A 0 is minimum and 120 is the maximum.

Time frame: at the recruitment and after 6 months

REM Sleep Pattern

This requires an instrument Zeo sleep monitor. Subjects are given instructions how to use it. Sleep sensor patches are supposed to be applied on forehead before going to sleep and the data of quality of sleep is captured overnight. The reported data captures the rapid eye movement (REM) sleep as a percentage.

Time frame: baseline and after 6 months

Deep Sleep

Time frame: At baseline and after 6 months

Light Sleep

Time frame: baseline and 6 months

Sleep Time - Awake

Time frame: at baseline and 6 months

Mini-Mental State Examination (MMSE) Change

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

Cerebrospinal Fluid Changes - Interleukin 6 (IL6)

IL-6 cytokine levels will be tested in cerebral spinal fluid (CSF) at baseline and 6 months after intervention.

Time frame: at baseline and after 6 months

Cerebrospinal Fluid Changes - Interleukin 10 (IL-10)

IL-10 will be tested in cerebral spinal fluid (CSF) at baseline and 6 months after intervention.

Time frame: at baseline and after 6 months

Niacin Metabolite in Urine - Niacin

Plasma and urine samples will be tested to report levels of niacin and its metabolites. Higher value indicates higher niacin levels

Time frame: at baseline and after 6 months

Niacin Metabolites in Urine - NAM Nicotinamide

Plasma and urine samples will be tested to report levels of niacin and its metabolites. Higher value indicates higher niacin levels

Time frame: at baseline and 6 months

Niacin Changes in Plasma - Niacin

Plasma and urine samples will be tested to report levels of niacin and its metabolites. Higher value indicates higher niacin levels.

Time frame: baseline and 6 months

Niacin Changes in Plasma - NUA Nicotinuric Acid

Plasma and urine samples will be tested to report levels of niacin and its metabolites. Higher value indicates higher niacin levels

Time frame: at baseline and 6 months

Cerebrospinal Fluid Changes - Interleukin 8 (IL8)

IL-8 cytokine levels will be tested in cerebral spinal fluid (CSF) at baseline and 6 months after intervention.

Time frame: at baseline and after 6 months

Niacin Metabolite in Urine - Nicotinuric Acid NUA

Plasma and urine samples will be tested to report levels of niacin and its metabolites. Higher value indicates higher niacin levels

Time frame: at baseline and after 6 months

CSF Fluid Changes - Interleukin 1B (IL-1B)

IL-1beta levels were tested in cerebral spinal fluid (CSF) at baseline and 6 months after intervention.

Time frame: at baseline and 6 months

Cerebrospinal Fluid (CSF) Changes - Macrophage Inflammatory Protein 1 Beta (MIP 1 Beta)

Inflammatory and non-inflammatory cytokines levels will be tested in cerebral spinal fluid (CSF) at baseline and 6 months after intervention. We are reporting levels of MIP-1 beta here.

Time frame: at baseline and after 6 months

Macrophage Changes

The blood is tested to report G-protein coupled receptor 109A (GPR109A) levels in macrophages in M1 and M2 populations.

Time frame: at baseline and after 6 months

Niacin Metabolite Changes in Plasma - Nicotinamide (NAM)

Plasma and urine samples will be tested to report levels of niacin and its metabolites. Higher value indicates higher niacin levels.

Time frame: at baseline and after 6 months

CSF Changes in Interferon Gamma (IF-gamma)

Inflammatory and non-inflammatory cytokines levels will be tested in cerebral spinal fluid (CSF) at baseline and 6 months after intervention. We are reporting levels of IF-gamma beta here.

Time frame: at baseline and after 6 months

CSF Changes - Tumor Necrosis Factor - Alpha (TNF-alpha)

Inflammatory and non-inflammatory cytokines levels will be tested in cerebral spinal fluid (CSF) at baseline and 6 months after intervention. We are reporting levels of TNF-alpha here.

Time frame: at baseline and after 6 months

Cerebral Spinal Fluid Changes - Interferon Gamma Induced Protein -10 (IP-10)

Inflammatory and non-inflammatory cytokines levels will be tested in cerebral spinal fluid (CSF) at baseline and 6 months after intervention. We are reporting levels of IP-10 here.

Time frame: at baseline and after 6 months

Cerebral Spinal Fluid (CSF) Changes - Monocyte Chemoattractant Protein 4 (MCP4)

Inflammatory and non-inflammatory cytokines levels will be tested in cerebral spinal fluid (CSF) at baseline and 6 months after intervention. We are reporting levels of MCP4 here.

Time frame: at baseline and after 6 months

Cerebral Spinal Fluid (CSF) Changes - MIP1-alpha

Inflammatory and non-inflammatory cytokines levels will be tested in cerebral spinal fluid (CSF) at baseline and 6 months after intervention. We are reporting levels of MIP1-alpha here.

Time frame: at baseline and after 6 months

Plasma Cytokines - IF Gamma

Inflammatory and non-inflammatory cytokines levels will be tested in plasma at baseline and 6 months after intervention. We are reporting levels of IF-gamma here.

Time frame: at baseline and after 6 months

Plasma Cytokines - IL-10

Inflammatory and non-inflammatory cytokines levels will be tested in plasma at baseline and 6 months after intervention. We are reporting levels of IL-10 here.

Time frame: at baseline and after 6 months

Plasma Cytokines - IL1-B

Inflammatory and non-inflammatory cytokines levels will be tested in plasma at baseline and 6 months after intervention. We are reporting levels of IL-1B here.

Time frame: at baseline and after 6 months

Plasma Cytokines - IL-6

Inflammatory and non-inflammatory cytokines levels will be tested in plasma at baseline and 6 months after intervention. We are reporting levels of IL-6 here.

Time frame: at baseline and after 6 months

Plasma Cytokines - IL-8

Inflammatory and non-inflammatory cytokines levels will be tested in plasma at baseline and 6 months after intervention. We are reporting levels of IL-8 here.

Time frame: at baseline and after 6 Months

Plasma Cytokines - TNF-alpha

Inflammatory and non-inflammatory cytokines levels will be tested in plasma at baseline and 6 months after intervention. We are reporting levels of TNF-alpha here.

Time frame: at baseline and after 6 months

Plasma Cytokines - IP-10

Inflammatory and non-inflammatory cytokines levels will be tested in plasma at baseline and 6 months after intervention. We are reporting levels of IP-10 here.

Time frame: at baseline and after 6 months

Plasma Cytokines - MCP-4

Inflammatory and non-inflammatory cytokines levels will be tested in plasma at baseline and 6 months after intervention. We are reporting levels of MCP-4 here.

Time frame: at baseline and after 6 months

Plasma Cytokines - MIP1-alpha

Inflammatory and non-inflammatory cytokines levels will be tested in plasma at baseline and 6 months after intervention. We are reporting levels of MIP1-alpha here.

Time frame: at baseline and after 6 months

Plasma Cytokines - MIP1-beta

Inflammatory and non-inflammatory cytokines levels will be tested in plasma at baseline and 6 months after intervention. We are reporting levels of MIP1-beta here.

Time frame: at baseline and after 6 months

Plasma Levels - Serotonin

Plasma serotonin levels

Time frame: at baseline and after 6 months