AtherosclerosisNCT02812238
Study to Evaluate the Effect of Nicotinamide Riboside on Immunity
A study testing Nicotinamide riboside (NR) in people with Atherosclerosis and Diabetes, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 39 years
- Conditions the study is for
- Atherosclerosis, Diabetes, Coronary Artery Disease
- What is being tested?
- Nicotinamide riboside (NR)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jun 2016to 28 Aug 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 39 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Atherosclerosis, Diabetes, Coronary Artery Disease
- Being tested
- Nicotinamide riboside (NR), Placebo
- Keywords
- Inflammasome, Sirt3, Nicotinamide Riboside, Fasting
- Medical subject headings
- Atherosclerosis, Diabetes Mellitus, Coronary Artery Disease, Fasting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotinamide riboside (NR)Dietary supplement
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | 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. Receives: Dietary Supplement: Nicotinamide riboside (NR); Drug: Placebo |
| Arm 2 | Experimental | 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. Receives: Dietary Supplement: Nicotinamide riboside (NR); Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean IL-1 Beta Release From Peripheral Blood Mononuclear Cells During Refeeding After 24 Hour Fast
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.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2016 (estimated)
- Study start23 Jun 2016
- Primary completion28 Aug 2018
- Study completion28 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Michael N Sack, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02812238
- Sponsor's protocol ID
- 160129
- Other IDs
- 16-H-0129
- Status last verified
- 3 Apr 2019
- First submitted
- 23 Jun 2016
- Last updated
- 17 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Traba J, Kwarteng-Siaw M, Okoli TC, Li J, Huffstutler RD, Bray A, Waclawiw MA, Han K, Pelletier M, Sauve AA, Siegel RM, Sack MN. Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects. J Clin Invest. 2015 Nov 3;125(12):4592-600. doi: 10.1172/JCI83260.
PubMed 26529255Canto C, Houtkooper RH, Pirinen E, Youn DY, Oosterveer MH, Cen Y, Fernandez-Marcos PJ, Yamamoto H, Andreux PA, Cettour-Rose P, Gademann K, Rinsch C, Schoonjans K, Sauve AA, Auwerx J. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012 Jun 6;15(6):838-47. doi: 10.1016/j.cmet.2012.04.022.
PubMed 22682224Brown KD, Maqsood S, Huang JY, Pan Y, Harkcom W, Li W, Sauve A, Verdin E, Jaffrey SR. Activation of SIRT3 by the NAD(+) precursor nicotinamide riboside protects from noise-induced hearing loss. Cell Metab. 2014 Dec 2;20(6):1059-68. doi: 10.1016/j.cmet.2014.11.003.
PubMed 25470550Han K, Singh K, Meadows AM, Sharma R, Hassanzadeh S, Wu J, Goss-Holmes H, Huffstutler RD, Teague HL, Mehta NN, Griffin JL, Tian R, Traba J, Sack MN. Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects. Cell Rep Med. 2023 Sep 19;4(9):101157. doi: 10.1016/j.xcrm.2023.101157. Epub 2023 Aug 15.
PubMed 37586364Wu J, Singh K, Lin A, Meadows AM, Wu K, Shing V, Bley M, Hassanzadeh S, Huffstutler RD, Schmidt MS, Blanco LP, Tian R, Brenner C, Pirooznia M, Kaplan MJ, Sack MN. Boosting NAD+ blunts TLR4-induced type I IFN in control and systemic lupus erythematosus monocytes. J Clin Invest. 2022 Mar 1;132(5):e139828. doi: 10.1172/JCI139828.
PubMed 35025762
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study to Evaluate the Effect of Nicotinamide Riboside on Immunity
- ClinicalTrials.gov ID
- NCT02812238
- Acronym / sponsor ID
- 160129
- Conditions
- Atherosclerosis, Diabetes, Coronary Artery Disease
- Keywords
- Inflammasome, Sirt3, Nicotinamide Riboside, Fasting
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 23 Jun 2016
- Primary completion
- 28 Aug 2018 (actual)
- Study completion
- 28 Aug 2018 (actual)
- First posted
- 24 Jun 2016 (estimated)
- Results
- Posted 17 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Dietary Supplement: Nicotinamide riboside (NR), Drug: PlaceboEither 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. |
| Arm 2 | Experimental | Dietary Supplement: Nicotinamide riboside (NR), Drug: PlaceboEither 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. |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Dietary supplement | Arm 1, Arm 2 |
| PlaceboPlacebo 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. | Drug | Arm 1, Arm 2 |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26529255Traba J, Kwarteng-Siaw M, Okoli TC, Li J, Huffstutler RD, Bray A, Waclawiw MA, Han K, Pelletier M, Sauve AA, Siegel RM, Sack MN. Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects. J Clin Invest. 2015 Nov 3;125(12):4592-600. doi: 10.1172/JCI83260.
- Background: PubMed 22682224Canto C, Houtkooper RH, Pirinen E, Youn DY, Oosterveer MH, Cen Y, Fernandez-Marcos PJ, Yamamoto H, Andreux PA, Cettour-Rose P, Gademann K, Rinsch C, Schoonjans K, Sauve AA, Auwerx J. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012 Jun 6;15(6):838-47. doi: 10.1016/j.cmet.2012.04.022.
- Background: PubMed 25470550Brown KD, Maqsood S, Huang JY, Pan Y, Harkcom W, Li W, Sauve A, Verdin E, Jaffrey SR. Activation of SIRT3 by the NAD(+) precursor nicotinamide riboside protects from noise-induced hearing loss. Cell Metab. 2014 Dec 2;20(6):1059-68. doi: 10.1016/j.cmet.2014.11.003.
- Derived from this study: PubMed 37586364Han K, Singh K, Meadows AM, Sharma R, Hassanzadeh S, Wu J, Goss-Holmes H, Huffstutler RD, Teague HL, Mehta NN, Griffin JL, Tian R, Traba J, Sack MN. Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects. Cell Rep Med. 2023 Sep 19;4(9):101157. doi: 10.1016/j.xcrm.2023.101157. Epub 2023 Aug 15.
- Derived from this study: PubMed 35025762Wu J, Singh K, Lin A, Meadows AM, Wu K, Shing V, Bley M, Hassanzadeh S, Huffstutler RD, Schmidt MS, Blanco LP, Tian R, Brenner C, Pirooznia M, Kaplan MJ, Sack MN. Boosting NAD+ blunts TLR4-induced type I IFN in control and systemic lupus erythematosus monocytes. J Clin Invest. 2022 Mar 1;132(5):e139828. doi: 10.1172/JCI139828.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael N Sack, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nicotinamide riboside (NR) in people with Atherosclerosis and Diabetes, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean IL-1 Beta Release From Peripheral Blood Mononuclear Cells During Refeeding After 24 Hour Fast (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02812238, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2019.