Systemic Lupus Erythematosus (Sle)Phase 1/2NCT06032923
Double-blind Placebo Controlled Study to Evaluate the Effect of NAD+ Boosting With Nicotinamide Riboside on Immunometabolism and Immunity in Systemic Lupus Erythematosus
A Phase 1/2 study testing Nicotinamide Riboside in people with Systemic Lupus Erythematosus (Sle), run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Study Description: Systemic lupus erythematosus (SLE) occurs predominantly in women and is driven by type I interferon dysregulation and neutrophil hyperresponsiveness. Neutrophils in females have reduced mitochondrial bioenergetic capacity which affects immunometabolism. Read more about this study
- Who is it for?
- Ages 18 to 120 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Systemic Lupus Erythematosus (Sle)
- What is being tested?
- Nicotinamide Riboside
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Mar 2024to 1 Aug 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 120 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- SLE subjects:
- Female subjects 18 years or older who meets > 3 of 11 modified Am. Coll. of Rheumatology (ACR) (1997) Revised Criteria for SLE and mild/moderate disease activity defined as an SLE Disease Activity Index 2000(SLEDAI 2K) between zero and less than or equal to 14 at screening;
- If on glucocorticoids, the dose must be less than or equal to 20 mg daily and stable for at least 4 weeks prior to screening;
- If on hydroxychloroquine or other antimalarials such as chloroquine or quinacrine, dose must have been stable for the 12 weeks prior to screening. The max. allowed doses - hydroxychloroquine 400 mg/day, chloroquine phosphate 500 mg/day and quinacrine 100 mg/day;
- If on immunosuppressive drugs (methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus); dose must have been stable for the 12 weeks prior to screening
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- Subjects of childbearing potential must agree to practice effective birth control for the duration of the study;
- Stated willingness to comply with all study procedures and availability for the duration of the study;
- Agreement to adhere to Lifestyle Considerations throughout study duration;
- Ability of subject to understand and the willingness to sign a written informed consent document.
- If on vitamin B3 or tryptophan supplementation at screening, willing to stop it at least 6 weeks before the baseline visit.
- Control subjects:
- Female subjects 18 years or older
- No history of autoimmune or inflammatory disease
- If on vitamin B3 or tryptophan supplementation at screening, willing to stop it at least 6 weeks before the blood draw visit.
Who cannot join
- SLE Subjects:
- Active renal or central nervous system disease or major renal or hepatic dysfunction;
- Treatment with rituximab, belimumab or any other biologic agent within the 6 months prior to screening
- Treatment with cyclophosphamide or IVIG within the 6 months prior to screening and or increase in glucocorticoid dose within 4 weeks of screening;
- Pregnancy or lactation (nursing)
- Treatment with another investigational drug or other intervention within 6 months of screening
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- Control Subjects:
- Inability to sign consent
- Pregnancy or nursing
- Pregnant women are excluded from participation on this study. Self-reported pregnancy status may be accepted from female control participants of child-bearing potential for a blood draw which is considered a minimal risk procedure.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Study Description:
Systemic lupus erythematosus (SLE) occurs predominantly in women and is driven by type I interferon dysregulation and neutrophil hyperresponsiveness. Neutrophils in females have reduced mitochondrial bioenergetic capacity which affects immunometabolism. Nicotinamide adenine dinucleotide (NAD)+ boosting with nicotinamide riboside blunts type 1 IFN activation in-vivo in monocytes of healthy subjects and ex-vivo in SLE subjects. These findings support the proposal of the hypothesis that NAD+ boosting by NR supplementation will modulate metabolic pathways in lupus and blunt type 1 interferon signaling. Moreover, as type 1 interferon drives endothelial dysfunction, linked to increased cardiovascular risk, the effect of NR on endothelial function will be examined.
Read more
Objectives:
Primary Objective: Evaluate the effect of NR vs. placebo on immunometabolic and inflammatory remodeling in female SLE subjects:
Exploratory Objective: Compare and characterize myeloid cell bioenergetic and immunometabolic profiles in healthy control and SLE female subjects
Endpoints:
Primary Endpoint:
The primary end point will be to assess the effect of NR on blunting type I IFN signaling by measuring monocytic secretion of IFN-beta secretion compared to baseline in response to placebo vs. NR supplemented in SLE study subjects.
Exploratory Endpoints:
Healthy control vs. SLE subjects:
- Compare type I IFN transcript profiles in monocytes and neutrophils at baseline and in response to activation.
- Assess cell bioenergetics including: 1) monocyte and neutrophil metabolic flux mass spectroscopy of 13C-glucose and 13Cglutamine analysis to investigate their metabolic fates; (iii) Mitochondrial oxygen consumption (using glucose, amino acid, and fatty acid substrates) and glycolysis rates.
SLE baseline vs. NR/placebo supplementation:
Baseline vs. 6 weeks of NR/placebo:
-Assess effect of NR on bioenergetics by measuring steady-state metabolite levels comparing changes in placebo vs. NR groups in monocytes and neutrophils.
Baseline vs. 12 weeks of NR/placebo:
- Whole blood NAD+ levels (batched and measured at the end of study enrollment period)
- Explore effects of NR on gene regulation using monocyte and neutrophils by RNA-seq and chromatin remodeling analysis.
- Determine the effect of NR vs placebo on endothelial dysfunction in SLE subjects
Read the detailed description
Study Description:
Systemic lupus erythematosus (SLE) occurs predominantly in women and is driven by type I interferon dysregulation and neutrophil hyper-responsiveness. Neutrophils in females have reduced mitochondrial bioenergetic capacity which affects immunometabolism. Nicotinamide adenine dinucleotide (NAD)+ boosting with nicotinamide riboside blunts type 1 IFN activation in-vivo in monocytes of healthy subjects and ex-vivo in SLE subjects. These findings support the proposal of the hypothesis that NAD+ boosting by NR supplementation will modulate metabolic pathways in lupus and blunt type 1 interferon signaling. Moreover, as type 1 interferon drives endothelial dysfunction, linked to increased cardiovascular risk, the effect of NR on endothelial function will be examined.
Objectives:
Primary Objective: Evaluate the effect of NR vs. placebo on immunometabolic and inflammatory remodeling in female SLE subjects:
Exploratory Objective: Compare and characterize myeloid cell bioenergetic and immunometabolic profiles in healthy control and SLE female subjects
Endpoints:
Primary Endpoint:
The primary end point will be to assess the effect of NR on blunting type I IFN signaling by measuring monocytic secretion of IFN-beta secretion compared to baseline in response to placebo vs. NR supplemented in SLE study subjects.
Exploratory Endpoints:
Healthy control vs. SLE subjects:
- Compare type I IFN transcript profiles in monocytes and neutrophils at baseline and in response to activation.
- Assess cell bioenergetics including: 1) monocyte and neutrophil metabolic flux mass spectroscopy of 13C-glucose and 13C-glutamine analysis to investigate their metabolic fates; (iii) Mitochondrial oxygen consumption (using glucose, amino acid, and fatty acid substrates) and glycolysis rates.
SLE baseline vs. NR/placebo supplementation:
Baseline vs. 6 weeks of NR/placebo:
-Assess effect of NR on bioenergetics by measuring steady-state metabolite levels comparing changes in placebo vs. NR groups in monocytes and neutrophils.
Baseline vs. 12 weeks of NR/placebo:
- Whole blood NAD+ levels (batched and measured at the end of study enrollment period)
- Explore effects of NR on gene regulation using monocyte and neutrophils by RNA-seq and chromatin remodeling analysis.
- Determine the effect of NR vs placebo on endothelial dysfunction in SLE subjects
- Conditions
- Systemic Lupus Erythematosus (Sle)
- Being tested
- Nicotinamide Riboside
- Keywords
- Lupus, Chronic Inflammation
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotinamide RibosideDietary supplement
The dietary supplement Nicotinamide Riboside or a placebo capsule in subjects with SLE. Niagen(R) is a commercially available form of nicotinamide riboside (NR)
| Study group | Role | What they receive |
|---|---|---|
| Healthy controls | No intervention | This group will not receive the dietary supplement or placebo. |
| Subjects with SLE - Active | Active comparator | This study group will take the dietary supplement Nicotinamide Riboside capsules. Receives: Dietary Supplement: Nicotinamide Riboside |
| Subjects with SLE - Placebo | Placebo comparator | This study group will take the Placebo. Receives: Dietary Supplement: Nicotinamide Riboside |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary end point will be to assess the effect of NR on blunting type I IFN signaling and cytokine secretion from placebo vs. NR supplemented subjects in monocytes comparing baseline (visit 1 to visit 3).
Type 1 IFN dysregulation is present in SLE. NAD+ boosting blunts type 1 interferon in healthy subjects in-vivo and in monocytes of SLE subjects ex-vivo. Completion of data collection time is by 01/2027.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2023
- Study start13 Mar 2024
- Primary completion1 Aug 2028 (estimated)
- Study completion1 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Lupus Erythematosus (Sle)Studies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Rachael J Klein, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06032923
- Sponsor's protocol ID
- 10001621
- Other IDs
- 001621-H
- Status last verified
- 29 Jul 2026
- First submitted
- 9 Sep 2023
- Last updated
- 31 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-blind Placebo Controlled Study to Evaluate the Effect of NAD+ Boosting With Nicotinamide Riboside on Immunometabolism and Immunity in Systemic Lupus Erythematosus
- ClinicalTrials.gov ID
- NCT06032923
- Acronym / sponsor ID
- 10001621
- Conditions
- Systemic Lupus Erythematosus (Sle)
- Keywords
- Lupus, Chronic Inflammation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 13 Mar 2024 (actual)
- Primary completion
- 1 Aug 2028 (estimated)
- Study completion
- 1 Aug 2028 (estimated)
- First posted
- 13 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study Description:
Systemic lupus erythematosus (SLE) occurs predominantly in women and is driven by type I interferon dysregulation and neutrophil hyperresponsiveness. Neutrophils in females have reduced mitochondrial bioenergetic capacity which affects immunometabolism. Nicotinamide adenine dinucleotide (NAD)+ boosting with nicotinamide riboside blunts type 1 IFN activation in-vivo in monocytes of healthy subjects and ex-vivo in SLE subjects. These findings support the proposal of the hypothesis that NAD+ boosting by NR supplementation will modulate metabolic pathways in lupus and blunt type 1 interferon signaling. Moreover, as type 1 interferon drives endothelial dysfunction, linked to increased cardiovascular risk, the effect of NR on endothelial function will be examined.
Objectives:
Primary Objective: Evaluate the effect of NR vs. placebo on immunometabolic and inflammatory remodeling in female SLE subjects:
Exploratory Objective: Compare and characterize myeloid cell bioenergetic and immunometabolic profiles in healthy control and SLE female subjects
Endpoints:
Primary Endpoint:
The primary end point will be to assess the effect of NR on blunting type I IFN signaling by measuring monocytic secretion of IFN-beta secretion compared to baseline in response to placebo vs. NR supplemented in SLE study subjects.
Exploratory Endpoints:
Healthy control vs. SLE subjects:
- Compare type I IFN transcript profiles in monocytes and neutrophils at baseline and in response to activation.
- Assess cell bioenergetics including: 1) monocyte and neutrophil metabolic flux mass spectroscopy of 13C-glucose and 13Cglutamine analysis to investigate their metabolic fates; (iii) Mitochondrial oxygen consumption (using glucose, amino acid, and fatty acid substrates) and glycolysis rates.
SLE baseline vs. NR/placebo supplementation:
Baseline vs. 6 weeks of NR/placebo:
-Assess effect of NR on bioenergetics by measuring steady-state metabolite levels comparing changes in placebo vs. NR groups in monocytes and neutrophils.
Baseline vs. 12 weeks of NR/placebo:
- Whole blood NAD+ levels (batched and measured at the end of study enrollment period)
- Explore effects of NR on gene regulation using monocyte and neutrophils by RNA-seq and chromatin remodeling analysis.
- Determine the effect of NR vs placebo on endothelial dysfunction in SLE subjects
Detailed description
Study Description:
Systemic lupus erythematosus (SLE) occurs predominantly in women and is driven by type I interferon dysregulation and neutrophil hyper-responsiveness. Neutrophils in females have reduced mitochondrial bioenergetic capacity which affects immunometabolism. Nicotinamide adenine dinucleotide (NAD)+ boosting with nicotinamide riboside blunts type 1 IFN activation in-vivo in monocytes of healthy subjects and ex-vivo in SLE subjects. These findings support the proposal of the hypothesis that NAD+ boosting by NR supplementation will modulate metabolic pathways in lupus and blunt type 1 interferon signaling. Moreover, as type 1 interferon drives endothelial dysfunction, linked to increased cardiovascular risk, the effect of NR on endothelial function will be examined.
Objectives:
Primary Objective: Evaluate the effect of NR vs. placebo on immunometabolic and inflammatory remodeling in female SLE subjects:
Exploratory Objective: Compare and characterize myeloid cell bioenergetic and immunometabolic profiles in healthy control and SLE female subjects
Endpoints:
Primary Endpoint:
The primary end point will be to assess the effect of NR on blunting type I IFN signaling by measuring monocytic secretion of IFN-beta secretion compared to baseline in response to placebo vs. NR supplemented in SLE study subjects.
Exploratory Endpoints:
Healthy control vs. SLE subjects:
- Compare type I IFN transcript profiles in monocytes and neutrophils at baseline and in response to activation.
- Assess cell bioenergetics including: 1) monocyte and neutrophil metabolic flux mass spectroscopy of 13C-glucose and 13C-glutamine analysis to investigate their metabolic fates; (iii) Mitochondrial oxygen consumption (using glucose, amino acid, and fatty acid substrates) and glycolysis rates.
SLE baseline vs. NR/placebo supplementation:
Baseline vs. 6 weeks of NR/placebo:
-Assess effect of NR on bioenergetics by measuring steady-state metabolite levels comparing changes in placebo vs. NR groups in monocytes and neutrophils.
Baseline vs. 12 weeks of NR/placebo:
- Whole blood NAD+ levels (batched and measured at the end of study enrollment period)
- Explore effects of NR on gene regulation using monocyte and neutrophils by RNA-seq and chromatin remodeling analysis.
- Determine the effect of NR vs placebo on endothelial dysfunction in SLE subjects
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy controls | No intervention | –This group will not receive the dietary supplement or placebo. |
| Subjects with SLE - Active | Active comparator | Dietary Supplement: Nicotinamide RibosideThis study group will take the dietary supplement Nicotinamide Riboside capsules. |
| Subjects with SLE - Placebo | Placebo comparator | Dietary Supplement: Nicotinamide RibosideThis study group will take the Placebo. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Female subjects 18 years or older who meets > 3 of 11 modified Am. Coll. of Rheumatology (ACR) (1997) Revised Criteria for SLE and mild/moderate disease activity defined as an SLE Disease Activity Index 2000(SLEDAI 2K) between zero and less than or equal to 14 at screening;
- If on glucocorticoids, the dose must be less than or equal to 20 mg daily and stable for at least 4 weeks prior to screening;
- If on hydroxychloroquine or other antimalarials such as chloroquine or quinacrine, dose must have been stable for the 12 weeks prior to screening. The max. allowed doses - hydroxychloroquine 400 mg/day, chloroquine phosphate 500 mg/day and quinacrine 100 mg/day;
- If on immunosuppressive drugs (methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus); dose must have been stable for the 12 weeks prior to screening
Key exclusion criteria (10 listed)
- Active renal or central nervous system disease or major renal or hepatic dysfunction;
- Treatment with rituximab, belimumab or any other biologic agent within the 6 months prior to screening
- Treatment with cyclophosphamide or IVIG within the 6 months prior to screening and or increase in glucocorticoid dose within 4 weeks of screening;
- Pregnancy or lactation (nursing)
- Treatment with another investigational drug or other intervention within 6 months of screening
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 RibosideThe dietary supplement Nicotinamide Riboside or a placebo capsule in subjects with SLE. Niagen(R) is a commercially available form of nicotinamide riboside (NR) | Dietary supplement | Subjects with SLE - Active, Subjects with SLE - Placebo |
Primary outcome
The primary end point will be to assess the effect of NR on blunting type I IFN signaling and cytokine secretion from placebo vs. NR supplemented subjects in monocytes comparing baseline (visit 1 to visit 3).
Time frame: 4 years
Type 1 IFN dysregulation is present in SLE. NAD+ boosting blunts type 1 interferon in healthy subjects in-vivo and in monocytes of SLE subjects ex-vivo. Completion of data collection time is by 01/2027.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Rachael J Klein, 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 Phase 1/2 study testing Nicotinamide Riboside in people with Systemic Lupus Erythematosus (Sle), 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 15 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 31 Jul 2026. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rebecca D Huffstutler, C.R.N.P. ((301) 594-1281, rebecca.huffstutler@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary end point will be to assess the effect of NR on blunting type I IFN signaling and cytokine secretion from placebo vs. NR supplemented subjects in monocytes comparing baseline (visit 1 to visit 3). (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Jul 2026.