"Pharmacokinetic Study of Nicotinamide Riboside"

Metabolic Disturbance Clinical Trial

Official title:

"Pharmacokinetic Study of Nicotinamide Riboside"

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02689882
• Other study ID #: HL126209-01S1
• Secondary ID: R21HL126209-01S1
• Status: Completed
• Phase: Phase 1
• First received: February 16, 2016
• Last updated: February 6, 2018
• Start date: November 2015
• Est. completion date: February 2016

Study information

• Verified date: February 2018
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: February 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Metabolic Disturbance

Intervention

Dietary Supplement:
• nicotinamide riboside
Nicotinamide riboside dose up-titration: Days 1 and 2: 250 mg by mouth daily; Days 3 and 4: 250 mg by mouth twice daily; Days 5 and 6: 500 mg by mouth twice daily; Days 7 and 8: 1000mg by mouth twice daily; Day 9: single dose of 1000mg by mouth followed by 24 hour pharmacokinetic study.

Locations

Country	Name	City	State
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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+ le — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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. Group mean values will be compared by paired t-test, with correction for multiple primary endpoints.	9 days
Primary	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.	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. Group mean values will be compared by paired t-test, with correction for multiple primary endpoints.	9 days
Secondary	Effect of nicotinamide riboside on serum potassium levels	Comparison of group mean serum potassium levels at day 1 (baseline) vs. day 9 (while on nicotinamide riboside 1000mg twice daily). Group mean potassium levels will be compared by paired t-test, with correction for multiple comparisons.	9 days
Secondary	Effect of nicotinamide riboside on serum creatine kinase levels	Comparison of group mean serum creatine kinase levels at day 1 (baseline) vs. day 9 (while on nicotinamide riboside 1000mg twice daily). Group mean creatine kinase levels will be compared by paired t-test, with correction for multiple comparisons.	9 days
Secondary	Effect of nicotinamide riboside on serum glucose levels	Comparison of group mean serum glucose levels at day 1 (baseline) vs. day 9 (while on nicotinamide riboside 1000mg twice daily). Group mean glucose levels will be compared by paired t-test, with correction for multiple comparisons.	9 days
Secondary	Effect of nicotinamide riboside on serum uric acid levels	Comparison of group mean serum uric acid levels at day 1 (baseline) vs. day 9 (while on nicotinamide riboside 1000mg twice daily). Group mean uric acid levels will be compared by paired t-test, with correction for multiple comparisons.	9 days
Secondary	Effect of nicotinamide riboside on serum alanine aminotransferase levels	Comparison of group mean serum alanine aminotransferase levels at day 1 (baseline) vs. day 9 (while on nicotinamide riboside 1000mg twice daily). Group mean alanine aminotransferase levels will be compared by paired t-test, with correction for multiple comparisons.	9 days