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

NCT06032923 · Status: RECRUITING · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 78

Last updated 2026-02-17

No results posted yet for this study

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)

Interventions

DIETARY_SUPPLEMENT

Nicotinamide Riboside

The dietary supplement Nicotinamide Riboside or a placebo capsule in subjects with SLE. Niagen(R) is a commercially available form of nicotinamide riboside (NR)

Sponsors & Collaborators

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

    lead NIH

Principal Investigators

  • Michael N Sack, M.D. · National Heart, Lung, and Blood Institute (NHLBI)

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Model
PARALLEL

Eligibility

Min Age
18 Years
Max Age
120 Years
Sex
FEMALE
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2024-03-13
Primary Completion
2028-08-01
Completion
2028-08-01

Countries

  • United States

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06032923 on ClinicalTrials.gov