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

Parkinson's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03462680
• Other study ID #: N1613-I
• Status: Completed
• Phase: N/A
• Start date: September 28, 2016
• Est. completion date: April 23, 2020

Study information

• Verified date: October 2021
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: April 23, 2020
• Est. primary completion date: April 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Dietary Supplement:
• niacin
Niacin or nicotinic acid 250 mg tablets

Other:
• placebo
placebo tablet

Locations

Country	Name	City	State
United States	Charlie Norwood VA Medical Center, Augusta, GA	Augusta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	at the recruitment and after 6 months
Primary	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.	baseline and after 6 months
Primary	Deep Sleep	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 deep sleep percentage.	At baseline and after 6 months
Primary	Light Sleep	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 light sleep percentage.	baseline and 6 months
Primary	Sleep Time - Awake	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 awake time during night sleep percentage.	at baseline and 6 months
Primary	Mini-Mental State Examination (MMSE) Change	It captures mental status and awareness of time, place and surrounding. A zero is minimum and 30 is maximum. Higher score indicates better cognition.	at baseline and after 6 months of treatment
Primary	Stroop Test Change	It captures understanding of color and its description within a certain time frame when letters and colors do not match. There are only two choices to pick from and the correct choices should be made to proceed to the next one. Correct choices are given one point and incorrect choices delete one point. Maximum number of correct choices per unit time are recorded. Three initial trials are given to understand the test. No minimum or maximum values. Higher numbers indicate better cognition.	at the baseline and after 6 months of intervention
Primary	Fatigue Severity Scale	Fatigue was rated from 0-7 in a fatigue questionnaire. A 0 being the least and 7 being the highest level of fatigue.	at baseline and after 6 months
Secondary	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.	at baseline and after 6 months
Secondary	Cerebrospinal Fluid Changes - Interleukin 10 (IL-10)	IL-10 will be tested in cerebral spinal fluid (CSF) at baseline and 6 months after intervention.	at baseline and after 6 months
Secondary	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	at baseline and after 6 months
Secondary	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	at baseline and 6 months
Secondary	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.	baseline and 6 months
Secondary	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	at baseline and 6 months
Secondary	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.	at baseline and after 6 months
Secondary	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	at baseline and after 6 months
Secondary	CSF Fluid Changes - Interleukin 1B (IL-1B)	IL-1beta levels were tested in cerebral spinal fluid (CSF) at baseline and 6 months after intervention.	at baseline and 6 months
Secondary	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.	at baseline and after 6 months
Secondary	Macrophage Changes	The blood is tested to report G-protein coupled receptor 109A (GPR109A) levels in macrophages in M1 and M2 populations.	at baseline and after 6 months
Secondary	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.	at baseline and after 6 months
Secondary	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.	at baseline and after 6 months
Secondary	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.	at baseline and after 6 months
Secondary	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.	at baseline and after 6 months
Secondary	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.	at baseline and after 6 months
Secondary	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.	at baseline and after 6 months
Secondary	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.	at baseline and after 6 months
Secondary	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.	at baseline and after 6 months
Secondary	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.	at baseline and after 6 months
Secondary	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.	at baseline and after 6 months
Secondary	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.	at baseline and after 6 Months
Secondary	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.	at baseline and after 6 months
Secondary	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.	at baseline and after 6 months
Secondary	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.	at baseline and after 6 months
Secondary	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.	at baseline and after 6 months
Secondary	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.	at baseline and after 6 months
Secondary	Plasma Levels - Serotonin	Plasma serotonin levels	at baseline and after 6 months