Double-blind Placebo Controlled Study to Evaluate the Effect of NAD+ Boosting With Nicotinamide Riboside on Immunometabolism and Immunity in Systemic Lupus Erythematosus

NCT06032923 | Recruiting Phase 1

• 2 other identifiers: 10001621001621-H
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief 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. 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

Conditions

Systemic Lupus Erythematosus (Sle)

Keywords

Lupus; Chronic Inflammation

Outcome Measures

Primary Outcomes (1)

• 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.

  4 years

Study Arms (3)

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.

Dietary Supplement: Nicotinamide Riboside

Subjects with SLE - Placebo

PLACEBO COMPARATOR

This study group will take the Placebo.

Dietary Supplement: Nicotinamide Riboside

Interventions

Nicotinamide Riboside DIETARY_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)

Subjects with SLE - Active; Subjects with SLE - Placebo

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Michael N Sack, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebecca D Huffstutler, C.R.N.P.

CONTACT

(301) 594-1281; rebecca.huffstutler@nih.gov

Michael N Sack, M.D.

CONTACT

(301) 402-9259; ms761k@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2023
• First Posted: September 13, 2023
• Study Start: March 13, 2024
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: February 17, 2026

Record last verified: 2026-02-04

Locations

US (1)