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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03462680
Recruitment Status : Completed
First Posted : March 12, 2018
Results First Posted : November 17, 2021
Last Update Posted : November 17, 2021
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Brief 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.


Condition or disease Intervention/treatment Phase
Parkinson's Disease Dietary Supplement: niacin Other: placebo Not Applicable

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: There are two arms, niacin 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: GPR109A and Parkinson's Disease: Role of Niacin in Outcome Measures
Actual Study Start Date : September 28, 2016
Actual Primary Completion Date : April 23, 2020
Actual Study Completion Date : April 23, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: niacin
Niacin 250 mg is compared to placebo tablet.
Dietary Supplement: niacin
Niacin or nicotinic acid 250 mg tablets
Other Name: vitamin B3

Placebo Comparator: placebo
placebo
Other: placebo
placebo tablet




Primary Outcome Measures :
  1. Unified Parkinson's Disease Rating Scale (UPDRS) Change [ Time Frame: at the recruitment and after 6 months ]
    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.

  2. REM Sleep Pattern [ Time Frame: baseline and after 6 months ]
    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.

  3. Deep Sleep [ Time Frame: At baseline and after 6 months ]
    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.

  4. Light Sleep [ Time Frame: baseline and 6 months ]
    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.

  5. Sleep Time - Awake [ Time Frame: at baseline and 6 months ]
    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.

  6. Mini-Mental State Examination (MMSE) Change [ Time Frame: at baseline and after 6 months of treatment ]
    It captures mental status and awareness of time, place and surrounding. A zero is minimum and 30 is maximum. Higher score indicates better cognition.

  7. Stroop Test Change [ Time Frame: at the baseline and after 6 months of intervention ]
    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.

  8. Fatigue Severity Scale [ Time Frame: at baseline and after 6 months ]
    Fatigue was rated from 0-7 in a fatigue questionnaire. A 0 being the least and 7 being the highest level of fatigue.


Secondary Outcome Measures :
  1. Cerebrospinal Fluid Changes - Interleukin 6 (IL6) [ Time Frame: at baseline and after 6 months ]
    IL-6 cytokine levels will be tested in cerebral spinal fluid (CSF) at baseline and 6 months after intervention.

  2. Cerebrospinal Fluid Changes - Interleukin 10 (IL-10) [ Time Frame: at baseline and after 6 months ]
    IL-10 will be tested in cerebral spinal fluid (CSF) at baseline and 6 months after intervention.

  3. Niacin Metabolite in Urine - Niacin [ Time Frame: at baseline and after 6 months ]
    Plasma and urine samples will be tested to report levels of niacin and its metabolites. Higher value indicates higher niacin levels

  4. Niacin Metabolites in Urine - NAM Nicotinamide [ Time Frame: at baseline and 6 months ]
    Plasma and urine samples will be tested to report levels of niacin and its metabolites. Higher value indicates higher niacin levels

  5. Niacin Changes in Plasma - Niacin [ Time Frame: baseline and 6 months ]
    Plasma and urine samples will be tested to report levels of niacin and its metabolites. Higher value indicates higher niacin levels.

  6. Niacin Changes in Plasma - NUA Nicotinuric Acid [ Time Frame: at baseline and 6 months ]
    Plasma and urine samples will be tested to report levels of niacin and its metabolites. Higher value indicates higher niacin levels

  7. Cerebrospinal Fluid Changes - Interleukin 8 (IL8) [ Time Frame: at baseline and after 6 months ]
    IL-8 cytokine levels will be tested in cerebral spinal fluid (CSF) at baseline and 6 months after intervention.

  8. Niacin Metabolite in Urine - Nicotinuric Acid NUA [ Time Frame: at baseline and after 6 months ]
    Plasma and urine samples will be tested to report levels of niacin and its metabolites. Higher value indicates higher niacin levels

  9. CSF Fluid Changes - Interleukin 1B (IL-1B) [ Time Frame: at baseline and 6 months ]
    IL-1beta levels were tested in cerebral spinal fluid (CSF) at baseline and 6 months after intervention.

  10. Cerebrospinal Fluid (CSF) Changes - Macrophage Inflammatory Protein 1 Beta (MIP 1 Beta) [ Time Frame: at baseline and after 6 months ]
    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.

  11. Macrophage Changes [ Time Frame: at baseline and after 6 months ]
    The blood is tested to report G-protein coupled receptor 109A (GPR109A) levels in macrophages in M1 and M2 populations.

  12. Niacin Metabolite Changes in Plasma - Nicotinamide (NAM) [ Time Frame: at baseline and after 6 months ]
    Plasma and urine samples will be tested to report levels of niacin and its metabolites. Higher value indicates higher niacin levels.

  13. CSF Changes in Interferon Gamma (IF-gamma) [ Time Frame: at baseline and after 6 months ]
    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.

  14. CSF Changes - Tumor Necrosis Factor - Alpha (TNF-alpha) [ Time Frame: at baseline and after 6 months ]
    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.

  15. Cerebral Spinal Fluid Changes - Interferon Gamma Induced Protein -10 (IP-10) [ Time Frame: at baseline and after 6 months ]
    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.

  16. Cerebral Spinal Fluid (CSF) Changes - Monocyte Chemoattractant Protein 4 (MCP4) [ Time Frame: at baseline and after 6 months ]
    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.

  17. Cerebral Spinal Fluid (CSF) Changes - MIP1-alpha [ Time Frame: at baseline and after 6 months ]
    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.

  18. Plasma Cytokines - IF Gamma [ Time Frame: at baseline and after 6 months ]
    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.

  19. Plasma Cytokines - IL-10 [ Time Frame: at baseline and after 6 months ]
    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.

  20. Plasma Cytokines - IL1-B [ Time Frame: at baseline and after 6 months ]
    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.

  21. Plasma Cytokines - IL-6 [ Time Frame: at baseline and after 6 months ]
    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.

  22. Plasma Cytokines - IL-8 [ Time Frame: at baseline and after 6 Months ]
    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.

  23. Plasma Cytokines - TNF-alpha [ Time Frame: at baseline and after 6 months ]
    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.

  24. Plasma Cytokines - IP-10 [ Time Frame: at baseline and after 6 months ]
    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.

  25. Plasma Cytokines - MCP-4 [ Time Frame: at baseline and after 6 months ]
    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.

  26. Plasma Cytokines - MIP1-alpha [ Time Frame: at baseline and after 6 months ]
    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.

  27. Plasma Cytokines - MIP1-beta [ Time Frame: at baseline and after 6 months ]
    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.

  28. Plasma Levels - Serotonin [ Time Frame: at baseline and after 6 months ]
    Plasma serotonin levels



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03462680


Locations
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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
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Principal Investigator: Chandramohan Wakade, MBBS Charlie Norwood VA Medical Center, Augusta, GA
  Study Documents (Full-Text)

Documents provided by VA Office of Research and Development:
Informed Consent Form  [PDF] January 21, 2020

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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT03462680    
Other Study ID Numbers: N1613-I
First Posted: March 12, 2018    Key Record Dates
Results First Posted: November 17, 2021
Last Update Posted: November 17, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: As 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.

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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
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Synucleinopathies
Neurodegenerative Diseases
Niacin
Vitamins
Micronutrients
Physiological Effects of Drugs
Vitamin B Complex
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents