Parkinson's Disease
Conditions
Keywords
Parkinson's disease, Niacin, Niacinamide, Niacin, Niacinamide
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.
Interventions
DIETARY_SUPPLEMENTNiacin
100mg tablets twice daily
DIETARY_SUPPLEMENTNiacinamide
100mg tablets twice daily
OTHERPlacebo
Placebo tablet twice daily
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Only Pharmacists keep the log of the drug dispensed. Everyone else is blinded.
Intervention model description
There are three arms, niacin, niacinamide and placebo. They are double blind and randomized.
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Unified Parkinson's Disease Rating Scale (UPDRS) Change | Baseline, 6 month, 12 month and 18 months | This is the Unified Parkinson's disease rating scale assessment. The investigators assess part III of the UPDRS regarding motor skills. The values reported are the averages of baseline, 6months, 12 months, and 18 months values combined for all the participants in that group. So, in the niacin and the niacinamide groups, it indicated the average of 8 values and in the control group it is the average of 12 values. A score is recorded according to the motor skills recorded ranging from 0-5 in each test, 0 being normal and 5 being affected most. Scores are given judging the motor skills. The score may range between 0-132. Lower scores indicate better outcome. |
| Mini-Mental State Examination (MMSE) Change | Baseline, 6 month, 12 month and 18 months | It captures mental status and awareness of time, place and surrounding. Score ranges from 0-30, 30 denotes the best score and best mental status. All the values in the group are pooled for an average score at baseline, 6 months, 12 months, and 18 months. Therefore, Niacin and Niacinamide groups each demonstrates average of 8 values while placebo group shows average of 12 values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analogue Fatigue Scale Changes | Baseline, 6 month, 12 month and 18 months | Fatigue is self-reported on the Visual analogue fatigue scale (VAFS). Participants were asked about how much fatigue they feel ranging from no fatigue (score 0) to extreme fatigue (score 10). Each participant was asked about this score at baseline, 6 months, 12 months, and 18 months visit. Data reported is the averages of all the scores from that group for all the time points. |
| Trail Making Test Time Change | Baseline, 6 month, 12 month and 18 months | 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. Each A and B demonstrates averages from baseline, 6 months, 12 months and 18 months of all the participants. Therefore, in the niacin group A and group B each show averages of 8 values while the control group shows averages of 12 values. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
Niacin: 100mg tablets twice daily | 2 |
| 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
Niacinamide: 100mg tablets twice daily | 2 |
| Group 3 - Placebo Wait-listed Arm Oral placebo twice daily x 18- months with assessments @ baseline, 6 month, 12 month and 18 months
Placebo: Placebo tablet twice daily | 3 |
| Total | 7 |
Baseline characteristics
| Characteristic | Group 1 - Niacin Arm | Group 2 - Niacinamide Arm | Group 3 - Placebo Wait-listed Arm | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 3 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Age, Continuous | 62 years STANDARD_DEVIATION 8 | 67.5 years STANDARD_DEVIATION 3.5 | 69.33 years STANDARD_DEVIATION 2.5 | 66.27 years STANDARD_DEVIATION 3 |
| Mini Mental examination | 30 units on a scale STANDARD_DEVIATION 0 | 28.5 units on a scale STANDARD_DEVIATION 2.5 | 30 units on a scale STANDARD_DEVIATION 0 | 29.5 units on a scale STANDARD_DEVIATION 0.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Region of Enrollment United States | 2 Participants | 2 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| step score | 20.4 seconds STANDARD_DEVIATION 0.4 | 13 seconds STANDARD_DEVIATION 2 | 10.4 seconds STANDARD_DEVIATION 2.2 | 14.6 seconds STANDARD_DEVIATION 4 |
| Trail making A | 35.5 seconds STANDARD_DEVIATION 5.5 | 72.5 seconds STANDARD_DEVIATION 31.5 | 49.33 seconds STANDARD_DEVIATION 21 | 52.44 seconds STANDARD_DEVIATION 18.69 |
| Trail making B | 81.5 seconds STANDARD_DEVIATION 9 | 150.5 seconds STANDARD_DEVIATION 65.5 | 198 seconds STANDARD_DEVIATION 203.22 | 143.33 seconds STANDARD_DEVIATION 58.57 |
| UPDRS III | 40.5 units on a scale. STANDARD_DEVIATION 9 | 20.5 units on a scale. STANDARD_DEVIATION 4 | 17.6 units on a scale. STANDARD_DEVIATION 8 | 26.2 units on a scale. STANDARD_DEVIATION 12 |
| Visual Analogue Fatigue Score | 6.5 score on a scale STANDARD_DEVIATION 0.5 | 5.5 score on a scale STANDARD_DEVIATION 0.5 | 7 score on a scale STANDARD_DEVIATION 3 | 6.3 score on a scale STANDARD_DEVIATION 1.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 | 0 / 3 |
| other Total, other adverse events | 0 / 2 | 0 / 2 | 0 / 3 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 | 0 / 3 |
Outcome results
Primary
Mini-Mental State Examination (MMSE) Change
It captures mental status and awareness of time, place and surrounding. Score ranges from 0-30, 30 denotes the best score and best mental status. All the values in the group are pooled for an average score at baseline, 6 months, 12 months, and 18 months. Therefore, Niacin and Niacinamide groups each demonstrates average of 8 values while placebo group shows average of 12 values.
Time frame: Baseline, 6 month, 12 month and 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 - Niacin Arm | Mini-Mental State Examination (MMSE) Change | 29.57 score on a scale | Standard Deviation 1.04 |
| Group 2 - Niacinamide Arm | Mini-Mental State Examination (MMSE) Change | 29.4 score on a scale | Standard Deviation 1.2 |
| Group 3 - Placebo Wait-listed Arm | Mini-Mental State Examination (MMSE) Change | 30 score on a scale | Standard Deviation 0 |
Primary
Unified Parkinson's Disease Rating Scale (UPDRS) Change
This is the Unified Parkinson's disease rating scale assessment. The investigators assess part III of the UPDRS regarding motor skills. The values reported are the averages of baseline, 6months, 12 months, and 18 months values combined for all the participants in that group. So, in the niacin and the niacinamide groups, it indicated the average of 8 values and in the control group it is the average of 12 values. A score is recorded according to the motor skills recorded ranging from 0-5 in each test, 0 being normal and 5 being affected most. Scores are given judging the motor skills. The score may range between 0-132. Lower scores indicate better outcome.
Time frame: Baseline, 6 month, 12 month and 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 - Niacin Arm | Unified Parkinson's Disease Rating Scale (UPDRS) Change | 40.5 score on a scale | Standard Deviation 10 |
| Group 2 - Niacinamide Arm | Unified Parkinson's Disease Rating Scale (UPDRS) Change | 20.5 score on a scale | Standard Deviation 2.5 |
| Group 3 - Placebo Wait-listed Arm | Unified Parkinson's Disease Rating Scale (UPDRS) Change | 17.5 score on a scale | Standard Deviation 12 |
Secondary
Trail Making Test Time Change
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. Each A and B demonstrates averages from baseline, 6 months, 12 months and 18 months of all the participants. Therefore, in the niacin group A and group B each show averages of 8 values while the control group shows averages of 12 values.
Time frame: Baseline, 6 month, 12 month and 18 months
Secondary
Visual Analogue Fatigue Scale Changes
Fatigue is self-reported on the Visual analogue fatigue scale (VAFS). Participants were asked about how much fatigue they feel ranging from no fatigue (score 0) to extreme fatigue (score 10). Each participant was asked about this score at baseline, 6 months, 12 months, and 18 months visit. Data reported is the averages of all the scores from that group for all the time points.
Time frame: Baseline, 6 month, 12 month and 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 - Niacin Arm | Visual Analogue Fatigue Scale Changes | 5.75 score on a scale | Standard Deviation 1.5 |
| Group 2 - Niacinamide Arm | Visual Analogue Fatigue Scale Changes | 5.75 score on a scale | Standard Deviation 1.5 |
| Group 3 - Placebo Wait-listed Arm | Visual Analogue Fatigue Scale Changes | 8.8 score on a scale | Standard Deviation 2.5 |