<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03808961</url>
  </required_header>
  <id_info>
    <org_study_id>NURE-013-18S</org_study_id>
    <nct_id>NCT03808961</nct_id>
  </id_info>
  <brief_title>Niacin for Parkinsons Disease</brief_title>
  <acronym>NAPS</acronym>
  <official_title>NAPS: Niacin for Parkinsons Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      (1) To examine the blood, urine and spinal fluid of persons with Parkinson's to look for&#xD;
      evidence of inflammation and; (2) whether 18 months of vitamin B3(niacin or niacinamide)&#xD;
      supplementation may reduce the inflammation and/or improve PD motor and non-motor symptoms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Number of people affected by Parkinson's disease is increasing each year. Vitamin B3&#xD;
      (Niacin/Niacinamide) supplement can be used to slow the progression of PD.&#xD;
&#xD;
      Inflammation plays a central role in Parkinson's disease (PD) pathology as evidenced by the&#xD;
      presence of microglia in the substantia nigra in post-mortem samples as well as activated&#xD;
      microglia and cytokines in clinical and animal studies. The use of non-aspirin non-steroidal&#xD;
      anti-inflammatory drugs was found to reduce the risk of PD. The investigators recently&#xD;
      identified an anti-inflammatory receptor GPR109A that is upregulated in PD. Niacin has a high&#xD;
      affinity for this receptor, suggesting that it (niacin) may play an important role in&#xD;
      reducing inflammation in PD. The investigators also found that individuals with PD have a&#xD;
      chronic niacin deficiency. In a three month trial at Augusta University (the investigators'&#xD;
      affiliate) the investigators demonstrated that niacin was helpful for PD patients in reducing&#xD;
      inflammatory macrophages and boosting the anti-inflammatory macrophages in blood.&#xD;
&#xD;
      In this VA-funded study, the investigators will determine the effect of 18 months&#xD;
      over-the-counter (OTC) niacin or niacinamide supplementation on inflammation (as assessed in&#xD;
      the blood and spinal fluid) and severity of the PD symptoms.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 1, 2020</start_date>
  <completion_date type="Anticipated">April 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>There are three arms, niacin, niacinamide and placebo. They are double blind and randomized.</intervention_model_description>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Only Pharmacists keep the log of the drug dispensed. Everyone else is blinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Unified Parkinson's Disease Rating Scale (UPDRS) change</measure>
    <time_frame>Baseline, 6 month, 12 month and 18 months</time_frame>
    <description>This is the Unified Parkinson's disease rating scale assessment. The investigators assess part III of the UPDRS regarding motor skills.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mini-Mental State Examination (MMSE) change</measure>
    <time_frame>Baseline, 6 month, 12 month and 18 months</time_frame>
    <description>It captures mental status and awareness of time, place and surrounding.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Macrophage and cytokine changes</measure>
    <time_frame>Baseline, 6 month, 12 month and 18 months</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Niacin changes</measure>
    <time_frame>Baseline, 6 month, 12 month and 18 months</time_frame>
    <description>Plasma and urine samples will be tested to report levels of niacin and its metabolites.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Visual analogue fatigue scale changes</measure>
    <time_frame>Baseline, 6 month, 12 month and 18 months</time_frame>
    <description>Fatigue is self-reported on the Visual analogue fatigue scale (VAFS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trail making test time change</measure>
    <time_frame>Baseline, 6 month, 12 month and 18 months</time_frame>
    <description>This is a timed test where the patient connects numbers in order for part A. Numbers and letters are connected interchangeably in past B. The time of B minus the time of A gives a measure for set shift change ability which is reduced in Parkinson's patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Arm strength and fatigue</measure>
    <time_frame>Baseline, 6 month, 12 month and 18 months</time_frame>
    <description>An electromyogram is performed on each arm of the patient. The test is recorded and aims to measure muscle strength and fatigue. Patients squeeze a bulb as hard as possible, then hold it for 30 seconds. This is done three times for each hand.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Parkinson's Disease</condition>
  <arm_group>
    <arm_group_label>Group 1 ? Niacin Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral 100 mg fixed dose twice daily x 18-months (200 mg total / day) with assessments @ baseline, 6 month, 12 month and 18 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 ? Niacinamide Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral 100 mg fixed dose twice daily (200 mg total / day) x 18-months with assessments @ baseline, 6 month, 12 month and 18 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3 ? Placebo Wait-listed Arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Oral placebo twice daily x 18- months with assessments @ baseline, 6 month, 12 month and 18 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Niacin</intervention_name>
    <description>100mg tablets twice daily</description>
    <arm_group_label>Group 1 ? Niacin Arm</arm_group_label>
    <other_name>Vitamin B3, Nicotinic acid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Niacinamide</intervention_name>
    <description>100mg tablets twice daily</description>
    <arm_group_label>Group 2 ? Niacinamide Arm</arm_group_label>
    <other_name>Vitamin B3, Nicotinamide</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo tablet twice daily</description>
    <arm_group_label>Group 3 ? Placebo Wait-listed Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  PD subjects will be adult men and women diagnosed with idiopathic mild to moderately&#xD;
             severe PD&#xD;
&#xD;
          -  The majority of PD subjects are expected to be &gt; 60 years old&#xD;
&#xD;
          -  Disease severity is defined as modified Hoehn &amp; Yahr Stages I-IV (while &quot;On&quot;)&#xD;
&#xD;
          -  PD is defined according to the UK Brain Bank Criteria made at least six months prior&#xD;
             to recruitment to the study&#xD;
&#xD;
          -  PD features include the presence of at least two of the four cardinal clinical&#xD;
             manifestations of the disease, which are:&#xD;
&#xD;
               -  tremor&#xD;
&#xD;
               -  rigidity&#xD;
&#xD;
               -  bradykinesia&#xD;
&#xD;
               -  disturbances of posture or gait, without any other known or suspected cause of&#xD;
                  Parkinsonism&#xD;
&#xD;
          -  Subjects should be stabilized on PD medication for at least 3 months before enrollment&#xD;
             into the study&#xD;
&#xD;
          -  Subjects' PD drug prescriptions will not be altered nor withheld during the study&#xD;
&#xD;
          -  The patient will have signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects will be excluded if they present with significant cognitive deficits&#xD;
&#xD;
          -  A MMSE score of 25 is considered substantial global cognitive impairment&#xD;
&#xD;
          -  Subjects will be excluded if they had previous brain surgery or other severe&#xD;
             neurological problems&#xD;
&#xD;
               -  intracerebral hemorrhage&#xD;
&#xD;
               -  traumatic brain injury&#xD;
&#xD;
               -  central nervous system malignancy&#xD;
&#xD;
               -  active central nervous system (CNS) infection&#xD;
&#xD;
               -  significant stroke&#xD;
&#xD;
               -  Alzheimer disease or any type of implanted stimulator including but not limited&#xD;
                  to Deep Brain Stimulator (DBS) or pacemaker&#xD;
&#xD;
          -  All subjects must be without evidence of dementia&#xD;
&#xD;
               -  defined as a score &gt; 24 the Mini-Mental State Examination and able to understand&#xD;
                  test instructions&#xD;
&#xD;
          -  Subjects must not have functional blindness (inability to participate in gait and&#xD;
             visuomotor assessments) or lower limb amputation higher than the forefoot or any&#xD;
             orthopedic problem that precludes performance of physical tests&#xD;
&#xD;
          -  Subjects must not have known allergy to vitamin B3&#xD;
&#xD;
          -  Significant cardiac, pulmonary, hepatic, gastrointestinal, renal disease, or&#xD;
             uncontrolled/advanced diabetes are also exclusionary factors, e.g.:&#xD;
&#xD;
               -  New York Heart Association Class III or IV congestive heart failure&#xD;
&#xD;
               -  endocarditis&#xD;
&#xD;
               -  pulmonary insufficiency symptomatic at rest or with mild physical exertion&#xD;
&#xD;
               -  acute or chronic hepatitis&#xD;
&#xD;
               -  renal failure requiring dialysis&#xD;
&#xD;
               -  second and third degree atrioventricular (AV) block&#xD;
&#xD;
               -  sick sinus syndrome&#xD;
&#xD;
          -  Subjects will be excluded if they are taking B3 but will be included if they are&#xD;
             taking B complex that has very low dose B3 (25 mg) which has minimal effects on&#xD;
             GPR109A (based on our unpublished observation)&#xD;
&#xD;
          -  Overall, the investigators will exercise clinical judgment to exclude a subject from&#xD;
             the study if, in the investigators' opinion, that a patient presents with a set of&#xD;
             comorbidities which renders unsuitability for the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chandramohan Wakade, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Charlie Norwood VA Medical Center, Augusta, GA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Charlie Norwood VA Medical Center, Augusta, GA</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30904</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>March 8, 2022</last_update_submitted>
  <last_update_submitted_qc>March 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Parkinson's disease, Niacin, Niacinamide</keyword>
  <keyword>Niacin</keyword>
  <keyword>Niacinamide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamins</mesh_term>
    <mesh_term>Niacin</mesh_term>
    <mesh_term>Niacinamide</mesh_term>
    <mesh_term>Nicotinic Acids</mesh_term>
    <mesh_term>Vitamin B Complex</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>At the investigators request, we will share the data</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>One year after the study is closed.</ipd_time_frame>
    <ipd_access_criteria>When we are ready to publish, the data will be available</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03808961
org study id: NURE-013-18S
nct id: NCT03808961
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
(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.
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: There are three arms, niacin, niacinamide and placebo. They are double blind and randomized.
primary purpose: Health Services Research
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Only Pharmacists keep the log of the drug dispensed. Everyone else is blinded.
measure: Unified Parkinson's Disease Rating Scale (UPDRS) change
time frame: Baseline, 6 month, 12 month and 18 months
description: This is the Unified Parkinson's disease rating scale assessment. The investigators assess part III of the UPDRS regarding motor skills.
measure: Mini-Mental State Examination (MMSE) change
time frame: Baseline, 6 month, 12 month and 18 months
description: It captures mental status and awareness of time, place and surrounding.
measure: Macrophage and cytokine changes
time frame: Baseline, 6 month, 12 month and 18 months
description: 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.
measure: Niacin changes
time frame: Baseline, 6 month, 12 month and 18 months
description: Plasma and urine samples will be tested to report levels of niacin and its metabolites.
measure: Visual analogue fatigue scale changes
time frame: Baseline, 6 month, 12 month and 18 months
description: Fatigue is self-reported on the Visual analogue fatigue scale (VAFS).
measure: Trail making test time change
time frame: Baseline, 6 month, 12 month and 18 months
description: This is a timed test where the patient connects numbers in order for part A. Numbers and letters are connected interchangeably in past B. The time of B minus the time of A gives a measure for set shift change ability which is reduced in Parkinson's patients.
measure: Arm strength and fatigue
time frame: Baseline, 6 month, 12 month and 18 months
description: An electromyogram is performed on each arm of the patient. The test is recorded and aims to measure muscle strength and fatigue. Patients squeeze a bulb as hard as possible, then hold it for 30 seconds. This is done three times for each hand.
arm group label: Group 1 ? Niacin Arm
arm group type: Active Comparator
description: Oral 100 mg fixed dose twice daily x 18-months (200 mg total / day) with assessments @ baseline, 6 month, 12 month and 18 months
arm group label: Group 2 ? Niacinamide Arm
arm group type: Active Comparator
description: Oral 100 mg fixed dose twice daily (200 mg total / day) x 18-months with assessments @ baseline, 6 month, 12 month and 18 months
arm group label: Group 3 ? Placebo Wait-listed Arm
arm group type: Placebo Comparator
description: Oral placebo twice daily x 18- months with assessments @ baseline, 6 month, 12 month and 18 months
intervention type: Dietary Supplement
intervention name: Niacin
description: 100mg tablets twice daily
arm group label: Group 1 ? Niacin Arm
other name: Vitamin B3, Nicotinic acid
intervention type: Dietary Supplement
intervention name: Niacinamide
description: 100mg tablets twice daily
arm group label: Group 2 ? Niacinamide Arm
other name: Vitamin B3, Nicotinamide
intervention type: Other
intervention name: Placebo
description: Placebo tablet twice daily
arm group label: Group 3 ? Placebo Wait-listed Arm
criteria: 
gender: All
minimum age: 35 Years
maximum age: N/A
healthy volunteers: No
last name: Chandramohan Wakade, MBBS
role: Principal Investigator
affiliation: Charlie Norwood VA Medical Center, Augusta, GA
facility: 
country: United States
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Vitamins
mesh term: Niacin
mesh term: Niacinamide
mesh term: Nicotinic Acids
mesh term: Vitamin B Complex
sharing ipd: Yes
ipd description: At the investigators request, we will share the data
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: One year after the study is closed.
ipd access criteria: When we are ready to publish, the data will be available