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出境医 / 临床实验 / Niacin for Parkinsons Disease (NAPS)

Niacin for Parkinsons Disease (NAPS)

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 Not Applicable

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
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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 : January 1, 2020
Estimated Primary Completion Date : November 1, 2023
Estimated Study Completion Date : April 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 Name: 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 Name: 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

Outcome Measures
Primary Outcome Measures :
  1. Unified Parkinson's Disease Rating Scale (UPDRS) change [ Time Frame: Baseline, 6 month, 12 month and 18 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.

  2. Mini-Mental State Examination (MMSE) change [ Time Frame: Baseline, 6 month, 12 month and 18 months ]
    It captures mental status and awareness of time, place and surrounding.

  3. Stroop test change [ Time Frame: Baseline, 6 month, 12 month and 18 months ]
    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 score is desired within given time. Three initial trials are given to understand the test.

  4. Sleep test change [ Time Frame: Baseline, 6 month, 12 month and 18 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.

  5. Macrophage and cytokine changes [ Time Frame: 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.

  6. Niacin changes [ Time Frame: Baseline, 6 month, 12 month and 18 months ]
    Plasma and urine samples will be tested to report levels of niacin and its metabolites.

  7. Cerebrospinal Fluid (CSF) changes [ Time Frame: Baseline, and 18 months ]
    Inflammatory and non-inflammatory cytokines levels will be tested in CSF at baseline and 18 months after intervention.


Eligibility Criteria
Layout table for eligibility information
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
  • 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
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Chandramohan Wakade, MBBS (706) 733-0188 ext 2378 Chandramohan.Wakade@va.gov
Contact: John C Morgan, MD (706) 733-0188 john.morgan@va.gov

Locations
Layout table for location information
United States, Georgia
Charlie Norwood VA Medical Center, Augusta, GA Recruiting
Augusta, Georgia, United States, 30904
Contact: Thomas J Hartney, MD    706-733-0188 ext 2510    Tom.Hartney@va.gov   
Contact: Christopher Rogers    (706) 733-188 ext 2508    Christopher.Rogers7@va.gov   
Principal Investigator: Chandramohan Wakade, MBBS         
Sponsors and Collaborators
VA Office of Research and Development
Investigators
Layout table for investigator information
Principal Investigator: Chandramohan Wakade, MBBS Charlie Norwood VA Medical Center, Augusta, GA
Tracking Information
First Submitted Date  ICMJE January 16, 2019
First Posted Date  ICMJE January 18, 2019
Last Update Posted Date April 19, 2021
Actual Study Start Date  ICMJE January 1, 2020
Estimated Primary Completion Date November 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2019)
  • Unified Parkinson's Disease Rating Scale (UPDRS) change [ Time Frame: Baseline, 6 month, 12 month and 18 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.
  • Mini-Mental State Examination (MMSE) change [ Time Frame: Baseline, 6 month, 12 month and 18 months ]
    It captures mental status and awareness of time, place and surrounding.
  • Stroop test change [ Time Frame: Baseline, 6 month, 12 month and 18 months ]
    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 score is desired within given time. Three initial trials are given to understand the test.
  • Sleep test change [ Time Frame: Baseline, 6 month, 12 month and 18 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.
  • Macrophage and cytokine changes [ Time Frame: 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 [ Time Frame: Baseline, 6 month, 12 month and 18 months ]
    Plasma and urine samples will be tested to report levels of niacin and its metabolites.
  • Cerebrospinal Fluid (CSF) changes [ Time Frame: Baseline, and 18 months ]
    Inflammatory and non-inflammatory cytokines levels will be tested in CSF at baseline and 18 months after intervention.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Niacin for Parkinsons Disease
Official Title  ICMJE NAPS: Niacin for Parkinsons Disease
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
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
Condition  ICMJE Parkinson's Disease
Intervention  ICMJE
  • Dietary Supplement: Niacin
    100mg tablets twice daily
    Other Name: Vitamin B3, Nicotinic acid
  • Dietary Supplement: Niacinamide
    100mg tablets twice daily
    Other Name: Vitamin B3, Nicotinamide
  • Other: Placebo
    Placebo tablet
Study Arms  ICMJE
  • 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
    Intervention: Dietary Supplement: Niacin
  • 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
    Intervention: Dietary Supplement: Niacinamide
  • 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
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 16, 2019)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 1, 2024
Estimated Primary Completion Date November 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Chandramohan Wakade, MBBS (706) 733-0188 ext 2378 Chandramohan.Wakade@va.gov
Contact: John C Morgan, MD (706) 733-0188 john.morgan@va.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03808961
Other Study ID Numbers  ICMJE NURE-013-18S
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: As the investigators request, we will share the data
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
Time Frame: One year after the study is closed.
Access Criteria: When we are ready to publish, the data will be available
Responsible Party VA Office of Research and Development
Study Sponsor  ICMJE VA Office of Research and Development
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Chandramohan Wakade, MBBS Charlie Norwood VA Medical Center, Augusta, GA
PRS Account VA Office of Research and Development
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP