Study to Evaluate the Effect of Nicotinamide Riboside on Immunity

August 26, 2019 updated by: National Heart, Lung, and Blood Institute (NHLBI)

Background:

The immune system controls how the body responds to infection or injury. Researchers want to see what effect a dietary supplement called nicotinamide riboside (NR) has on the immune system. A study showed that fasting has a good effect on immune cell health in healthy people. And when immune cells were exposed to NR they had a similar positive response as with fasting. Researchers want to see if healthy people have the same effects from NR and fasting, and if those effects last.

Objectives:

To see if taking nicotinamide riboside will have the same healthy immune system effects as fasting. To see if these good effects continue even after eating again.

Eligibility:

Healthy volunteers ages 18 - 39 years

Design:

Participants will be screened with medical history, physical exam, and blood tests. Women will have a urine pregnancy test.

Participants will take 4 pills of either NR or a placebo once a day for 1 week.

On day 6, they will not eat or drink anything.

On day 7, they will have a study visit to give a blood sample before and after eating a meal at the clinic.

They will also give a urine sample.

Participants will stop taking the pills for 1 2 weeks.

Participants will take either NR or a placebo once a day for 1 week.

They will repeat day 6 and day 7 of the first week.

Participants will get NR once and placebo once, but will not know which they are taking.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Intermittent caloric restriction or fasting has numerous health effects including the reduction in numerous cardiovascular disease risk factors. The cellular programs activated by caloric restriction are similarly turned on in preclinical studies in response to a 24-hour fast. We have found that a beneficial effect of 24-hour fasting is that it blunts the activation of a component of the immune system, termed the Nod-like receptor family protein 3 (NLRP3) Inflammasome. This inflammasome, as a mediator of sterile inflammation, is associated with the development of diabetes and atherosclerosis. At the same time, we found that refeeding after the 24-hour fast significantly increased NLRP3 protein levels, IL-1Beta, and TNF signaling, and that fasting blunted the NLRP3 inflammasome response, in association with the activation of a fasting sensing protein called SIRT3. Interestingly, a recently discovered naturally occurring form of vitamin B3, called nicotinamide riboside (NR), has been found to activate SIRT3. We found that NR reproduces the NLRP3 inflammasome blunting effect of fasting when administered to primary human monocytes/macrophages in culture. Putting this together, it would be interesting to evaluate whether the administration of NR to human subjects would replicate the fasting blunting effect on the NLRP3 inflammasome. Interestingly, at the same time, it has recently been found, in a preclinical study, that the NLRP3 protein can orchestrate differentiation of naive T- cells into Th2 cells. We therefore propose to more broadly examine the effects of NR administration on myeloid and lymphoid cell biology in healthy volunteers.

Study Type

Interventional

Enrollment (Actual)

38

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 39 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • INCLUSION CRITERIA:

As this is a pilot study, the age-range and BMI range of subjects will be restricted to potentially reduce metabolic variables associated with a wide age- and BMI-range.

  • Males and females between the ages of 18 and 39
  • BMI between 18.5 and 29.9
  • Agrees to comply with study procedures and maintain current level of physical activity and dietary intake throughout the study.
  • Female subjects of child-bearing ability willing to commit to reliable contraception while participating in the study.

EXCLUSION CRITERIA:

  • Subjects with an acute or chronic illness as per history, on laboratory analysis or requiring medications to manage disease.
  • Subjects taking vitamins or supplements or any medications, except oral contraceptives, within 4 weeks of participation into this study.
  • BMI <18.5 or >29.9.
  • Female subjects who are pregnant or lactating.
  • Subjects who have donated blood or participated in another clinical trial involving blood draws in the last 8 weeks.
  • Subjects who use nicotine products including chewing tobacco, vaporizer, gum, cigarette or patch form within three months.
  • Any other medical condition that, in the opinion of the Principal Investigator, might put the subject at risk of harm during the study or might adversely affect the interpretation of the study data.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1
Either NR at 1000mg/day or placebo for one week, followed by a washout period of 2-3 weeks, then a crossover to placebo or NR at 1000mg/day for one additional week. The end point was analyzed at end of each treatment.
Dietary supplement: Nicotinamide riboside (NR)
NR at dose of 1000mg/day will be given for a period of 7 days in a double blinded fashion either from the start of tx or after 1 week of placebo pills.
Drug: Placebo
Placebo capsule daily for a period of 7 days in a double blinded fashion either from the start of tx or after 1 week of NR at a dose of 1000mg/day.
Experimental: Arm 2
Either NR at 1000mg/day or placebo for one week, followed by a washout period of 2-3 weeks, then a crossover to placebo or NR at 1000mg/day for one additional week. The end point was analyzed at end of each treatment.
Dietary supplement: Nicotinamide riboside (NR)
NR at dose of 1000mg/day will be given for a period of 7 days in a double blinded fashion either from the start of tx or after 1 week of placebo pills.
Drug: Placebo
Placebo capsule daily for a period of 7 days in a double blinded fashion either from the start of tx or after 1 week of NR at a dose of 1000mg/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean IL-1 Beta Release From Peripheral Blood Mononuclear Cells During Refeeding After 24 Hour Fast
Time Frame: 4 weeks
The IL- 1beta secretion is measured in response to fasting, refeeding and administration of Nicotinamide Riboside (or placebo). Nicotinamide riboside acts as a fasting mimetic, and is supposed to maintain the reduction of IL-1 beta secretion (indicating NLRP3 inflammasome activation) induced by fasting. 1000 mg of Nicotinamide riboside on a daily basis is given to the subjects for a period of 7-10 days.
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 23, 2016

Primary Completion (Actual)

August 28, 2018

Study Completion (Actual)

August 28, 2018

Study Registration Dates

First Submitted

June 23, 2016

First Submitted That Met QC Criteria

June 23, 2016

First Posted (Estimate)

June 24, 2016

Study Record Updates

Last Update Posted (Actual)

September 17, 2019

Last Update Submitted That Met QC Criteria

August 26, 2019

Last Verified

April 3, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 160129
  • 16-H-0129

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Coronary Artery Disease

Clinical Trials on Nicotinamide riboside (NR)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Liberia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe