Nicotinamide Riboside for Systemic Lupus Erythematosus
Double-blind Placebo Controlled Study to Evaluate the Effect of NAD+ Boosting With Nicotinamide Riboside on Immunometabolism and Immunity in Systemic Lupus Erythematosus
Recruiting
Phase 1Phase 2Interventional Study
Systemic Lupus Erythematosus (Sle)
Prior Safety Data
This treatment has already been tested in at least one earlier human trial.
Healthy Volunteers Welcome
You do not need to have the condition being studied to take part.
Ready to participate?
Review the details below, then apply to join this clinical trial.
At a Glance
Age
18 – 120
Sex
Female
Trial phase
Phase 1/2
Study type
Interventional
Purpose
Treatment
Participants needed
78 (estimated)
Sponsor
National Heart, Lung, and Blood Institute (NHLBI) · NIH
Who this trial is looking for
This trial is looking for women with systemic lupus erythematosus to compare the effects of a supplement called nicotinamide riboside with a placebo. Participants will undergo assessments to see how this treatment affects immune responses and metabolism.
Are You a Good Fit for This Trial?
You may be able to join if
I am a female aged 18 or older.
I have been diagnosed with systemic lupus erythematosus.
I meet more than 3 of the 11 criteria for SLE.
I have mild to moderate disease activity.
I have stable doses of certain medications for at least 12 weeks.
I agree to practice effective birth control during the study.
I am willing to follow study procedures.
You may not be able to join if
I have active renal or central nervous system disease.
I have major liver problems or renal dysfunction.
I have taken certain biologic medications in the last 6 months.
I am pregnant or breastfeeding.
I have taken experimental drugs in the last 6 months.
Summarized in plain language from this trial's official eligibility criteria.
The full criteria are further down this page — only the research team can
confirm whether you qualify.
Think this trial could be right for you?
Answer a few quick questions to see if you may meet the eligibility requirements.
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…
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
Trial Locations
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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 dise…
* 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.
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