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RecruitingPhase 1 / Phase 2

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years to 120 Years
Sex
Female only
Healthy volunteers
Accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests whether nicotinamide riboside (NR), a supplement, changes how immune cells use energy and reduces signals that cause inflammation in women with lupus. It compares NR with a placebo, which has no active study ingredient, and checks blood vessel function. Women age 18 or older with lupus and healthy women for comparison may join.

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

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Women with lupus must be 18 or older, meet at least 4 of 11 listed lupus criteria, and have a lupus activity score from 0 to 14.
  • If taking steroids, the dose must be 20 mg a day or less and unchanged for at least 4 weeks before screening.
  • If taking antimalarial drugs for lupus, doses must be unchanged for 12 weeks before screening. Daily limits are 400 mg for hydroxychloroquine, 500 mg for chloroquine phosphate, and 100 mg for quinacrine.
  • If taking drugs that lower immune system activity, such as methotrexate or mycophenolate, doses must be unchanged for 12 weeks before screening.
  • Women with lupus who can become pregnant must agree to use effective birth control during the study.
  • Women with lupus must understand and sign the consent form, follow study procedures and lifestyle rules, and be available for the whole study.
  • Healthy comparison volunteers must be women age 18 or older with no history of inflammatory disease or disease in which the immune system attacks the body.
  • Anyone taking vitamin B3 or tryptophan supplements must stop at least 6 weeks before the first study visit for lupus participants or the blood draw for healthy volunteers.

Who can't join

  • For women with lupus: active kidney, brain, or spinal cord disease, or major problems with kidney or liver function.
  • For women with lupus: rituximab, belimumab, or another biologic drug within 6 months before screening. Biologics are medicines made from living cells.
  • For women with lupus: cyclophosphamide or IVIG, an antibody treatment given into a vein, within 6 months before screening.
  • For women with lupus: an increase in steroid dose within 4 weeks before screening.
  • For women with lupus: another experimental drug or treatment within 6 months before screening.
  • For all participants: pregnancy or breastfeeding.
  • For healthy comparison volunteers: unable to sign the consent form.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

* INCLUSION CRITERIA: 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. EXCLUSION CRITERIA: 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.

Study sites (1)

MD