Clinical trial NCT02689882: "Pharmacokinetic Study of Nicotinamide Riboside"
Official title: "Pharmacokinetic Study of Nicotinamide Riboside"
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metabolic Disturbance
Keywords: nicotinamide riboside
nicotinamide ribonucleoside
Nicotinamide-Adenine Dinucleotide
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2016-02-24
Enrollment: 8
Sex: ALL
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Nicotinamide riboside (NR) has been available over the counter as a nutraceutical (Niagen®, ChromaDex, Inc.) since the summer of 2013. However, classical pharmacokinetic (PK) data for NR have not been reported in humans. This study will use a recently-developed, whole blood assay for NR to assess the pharmacokinetics of NR at a maximum dose of 1000 mg twice daily, and will collect history, physical examination and laboratory data to determine the safety and tolerability of NR in eight, healthy volunteers. In addition, whole blood nicotinamide adenine dinucleotide (NAD) levels will be measured at each time point, to determine whether this NR dose significantly raises whole blood NAD levels.

Detailed description: 1. On Day 1, participants will have a baseline assessment, including blood pressure and heart rate, as well as baseline assessment of "safety" labs: complete blood count with white blood count differential and platelets, serum chemistry panel (sodium, potassium, chloride, glucose, blood urea nitrogen and creatinine), uric acid, creatine kinase, aspartate aminotransferase and alanine aminotransferase, and lactate dehydrogenase.
2. Participants will receive 250 mg nicotinamide riboside (NR) by mouth daily on Days 1-2, 250 mg NR by mouth twice daily on Days 3-4, 500 mg NR twice daily by mouth on Days 5-6 and 1000 mg NR twice daily by mouth on Days 7-8.
3. On Day 2, a blood sample will be obtained from each participant to measure serum chemistry panel to assess for the possibility of hyperkalemia and hyperglycemia. In addition, an instant read potassium will be measured using a point-of-care device available on the University of Washington (UW) General Clinical Research Center (GCRC). If the potassium is greater than 5.5, a repeat value and an ECG will be performed and the Study Investigator. If it is greater than 6.0, the Study Investigator will evaluate the subject for admission.
4. On Day 9 prior to receiving their morning dose, participants will be admitted to the UW GCRC for an overnight stay.

   1. In the UW GCRC, the participants will receive the last 1000 mg dose of NR at time=0.
   2. Blood samples will be collected at time = 30 minutes and at 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours.
   3. Whole blood samples will be frozen at -80 degrees C until assayed for NR and NAD+.
   4. "Safety labs" performed on Day 1 will be repeated

Eligibility criteria: Inclusion Criteria:

* Healthy, adult (age 21-50 years), male or female
* Willing and able to provide informed consent

Exclusion Criteria:

* Current smoking
* Receiving concurrent medications or supplements
* History of liver, renal, cardiovascular, endocrine, or neurological disease
* Known allergy to niacin or nicotinamide ribosome
* Unwilling to refrain from drinking alcohol during the duration of the study

Primary outcomes:
measure: Percent change in the average steady state concentration (Css) of nicotinamide riboside (NR) on day 9 (following up titration of nicotinamide riboside to 1000 mg by mouth twice daily) compared to pre-dose baseline.
timeFrame: 9 days
measure: Percent change in the average steady state concentration (Css) of nicotinamide adenine dinucleotide (NAD) on day 9 (following up titration of nicotinamide riboside to 1000 mg by mouth twice daily) compared to pre-dose baseline.
timeFrame: 9 days
Secondary outcomes:
measure: Effect of nicotinamide riboside on serum potassium levels
timeFrame: 9 days
measure: Effect of nicotinamide riboside on serum creatine kinase levels
timeFrame: 9 days
measure: Effect of nicotinamide riboside on serum glucose levels
timeFrame: 9 days
measure: Effect of nicotinamide riboside on serum uric acid levels
timeFrame: 9 days
measure: Effect of nicotinamide riboside on serum alanine aminotransferase levels
timeFrame: 9 days
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Washington
name: Kevin D O'Brien, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: Rong Tian, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Airhart SE, Shireman LM, Risler LJ, Anderson GD, Nagana Gowda GA, Raftery D, Tian R, Shen DD, O'Brien KD. An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers. PLoS One. 2017 Dec 6;12(12):e0186459. doi: 10.1371/journal.pone.0186459. eCollection 2017.