Nicotinamide Riboside for Systemic Lupus Erythematosus (SLE)

Overseen By Michael N Sack, M.D.

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Must not be taking: Biologics, Cyclophosphamide, IVIG, others

Disqualifiers: Active renal, CNS disease, pregnancy, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

78 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Nicotinamide Riboside (NR) might benefit women with systemic lupus erythematosus (SLE), a condition where the immune system attacks healthy tissues. Researchers aim to determine if NR can enhance the body's energy systems and reduce immune signals that contribute to inflammation in SLE. The trial will compare NR's effects to a placebo (a harmless pill with no active ingredient) to assess its impact on immune health and blood vessel function. Women with SLE who have stable symptoms and treatment, and who can adhere to the study's schedule, may be suitable candidates. As a Phase 1, Phase 2 trial, this research focuses on understanding NR's function in people and measuring its effectiveness in an initial group, offering participants a chance to contribute to groundbreaking lupus research.

Will I have to stop taking my current medications?

The trial requires that if you are taking vitamin B3 or tryptophan supplements, you must stop them at least 6 weeks before the baseline visit. Other medications like glucocorticoids, antimalarials, and immunosuppressive drugs must have stable doses for a certain period before screening.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that Nicotinamide Riboside (NR), a type of vitamin B3, is generally safe for use. Studies have found it usually causes fewer side effects than similar substances. In past research, participants taking NR reported no serious health problems, suggesting it might be safe, though it is still under study for certain conditions.

Researchers are also examining NR for its potential to lower inflammation and boost the immune system. This is particularly important for individuals with systemic lupus erythematosus (SLE), the focus of this study. The safety results from earlier studies are encouraging, but as with all clinical trials, monitoring for any unexpected effects remains crucial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lupus?

Nicotinamide Riboside is unique because it targets the body's cellular energy production, which is a novel approach for treating Systemic Lupus Erythematosus (SLE). Unlike standard treatments like corticosteroids or immunosuppressants that mainly focus on dampening the immune response, Nicotinamide Riboside boosts mitochondrial function, potentially improving overall cellular health and reducing inflammation in a different way. Researchers are excited about this treatment because it could offer a new, less immune-suppressing option for managing SLE, potentially leading to fewer side effects and improved quality of life for patients.

What evidence suggests that Nicotinamide Riboside might be an effective treatment for SLE?

Research has shown that nicotinamide riboside (NR) can reduce inflammation by lowering the levels of proteins that signal inflammation in both healthy individuals and those with systemic lupus erythematosus (SLE). In SLE, a protein called type I interferon, which can cause immune problems, is often too active. Laboratory tests found that NR reduces the activity of type I interferon in the immune cells of healthy individuals and in cells from SLE patients. This suggests that NR might help calm the immune system in people with lupus. Additionally, NR increases levels of NAD+, a molecule important for cell energy, which could improve immune cell function and potentially help manage SLE symptoms. Participants in this trial with SLE will receive either NR or a placebo to further evaluate these effects. ^{6 7 8 9 10}

Who Is on the Research Team?

Michael N Sack, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Are You a Good Fit for This Trial?

This trial is for women over 18 with mild to moderate Systemic Lupus Erythematosus (SLE), meeting specific criteria, and not on certain immunosuppressive drugs or recent biologic agents. They must have stable medication doses, agree to effective birth control, and commit to the study's duration without major organ dysfunction.

Inclusion Criteria

I am willing and able to follow all study rules and attend all appointments.

The subject must demonstrate comprehension and agree to sign a formalized informed consent document.

I have never had an autoimmune or inflammatory disease.

Exclusion Criteria

I haven't taken vitamin B3 or tryptophan supplements in the last 6 weeks.

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.

I am unable to give my consent for treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nicotinamide Riboside or placebo for 12 weeks to evaluate its effect on immunometabolism and immunity in SLE subjects

12 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nicotinamide Riboside

Trial Overview The trial tests if Nicotinamide Riboside (NR) can improve immune system metabolism in SLE by boosting NAD+ levels. It compares NR's effects on inflammatory responses and energy production in cells against a placebo over a period of up to 12 weeks.

How Is the Trial Designed?

Group I: Healthy controls Active Control 1 Intervention

This group will not receive the dietary supplement or placebo.

Group II: Subjects with SLE - Active Active Control 1 Intervention

This study group will take the dietary supplement Nicotinamide Riboside capsules.

Group III: Subjects with SLE - Placebo Placebo Group 1 Intervention

This study group will take the Placebo.

Nicotinamide Riboside is already approved in United States, European Union for the following indications:

Approved in United States as Niagen for:

• Dietary supplement for general health and wellness

Approved in European Union as Niagen for:

• Dietary supplement for general health and wellness

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Early administration of low-dose linomide significantly reduced autoantibody levels by 50-64% in an animal model of systemic lupus erythematosus (SLE), indicating its potential efficacy in preventing disease progression when given before disease onset.

Linomide was ineffective when administered during later stages of SLE, suggesting that its therapeutic benefits are limited to early intervention, and the effects diminished after treatment cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of experimental systemic lupus erythematosus with linomide. Zandman-Goddard, G., George, J., Levy, Y., et al.[2017]

This study involves a prospective randomized trial with 12 patients suffering from systemic lupus erythematosus (SLE) and nephritis, focusing on the effects of monthly intravenous cyclophosphamide administration.

Preliminary data suggests that cyclophosphamide may be a potential treatment option for managing SLE-related nephritis, although further results are needed to assess its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cyclophosphamide pulse therapy of systemic lupus erythematosus with renal involvement]. Hein, R., Neumann, KH., Koch, KM., et al.[2014]

In a clinical trial involving 51 patients with proliferative lupus nephritis, leflunomide (LEF) showed an 80% total response rate and a 40% complete remission rate, comparable to 75% and 25% respectively for IV cyclophosphamide, indicating LEF's efficacy as an induction therapy.

LEF was generally well-tolerated, though some patients experienced adverse events like infections and alopecia, highlighting the need for further research on its long-term safety and effectiveness in maintenance therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of proliferative lupus nephritis with leflunomide and steroid: a prospective multi-center controlled clinical trial]. Cui, TG., Hou, FF., Ni, ZH., et al.[2018]

Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE) that requires tailored treatment based on the specific type of LN, with traditional therapies including cyclophosphamide and prednisone being effective but associated with significant side effects.

Recent clinical trials are exploring new treatment options for LN that aim to improve efficacy while reducing toxicity, addressing the urgent need for safer alternatives given the high risk of progression to end-stage renal disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of proliferative and membranous lupus nephritis: review of key clinical trials. Alshayeb, H., Wall, BM., Gosmanova, EO.[2011]

In a study involving mice with established lupus nephritis, ribavirin significantly improved survival rates and reduced harmful antibodies against DNA, indicating its potential as a therapeutic option for this condition.

Ribavirin also reversed proteinuria, a common symptom of kidney damage in lupus nephritis, while other antiviral agents tested did not show effectiveness at the dosages used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribavirin: efficacy in the treatment of murine autoimmune disease. Klassen, LW., Budman, DR., Williams, GW., et al.[2019]

Citations

1. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/htmlSearchedFile.aspx?Query=Systemic%20Lupus%20Erythematosus%2013&status=&gender=Select%20One&Inst=&age=&healthyVolunteer=0

NIH Clinical Center: Search the Studies 001621-H Double-blind Placebo Controlled Study to Evaluate the Effect of NAD+ Boosting with Nicotinamide Riboside on Immunometabolism and Immunity in Systemic ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06032923

NCT06032923 | Double-blind Placebo Controlled Study to ... Systemic lupus erythematosus (SLE) occurs predominantly in women and is driven by type I interferon dysregulation and neutrophil hyperresponsiveness.

3. investors.chromadex.com investors.chromadex.com/news/news-details/2023/A-Milestone-Clinical-Study-Reveals-that-Elevating-Nicotinamide-Adenine-Dinucleotide-NAD-with-Nicotinamide-Riboside-NR-Supplementation-Effectively-Reduces-Inflammation-in-Both-Healthy-Subjects-and-Immune-Cells-Derived-from-Psoriasis-Patients/default.aspx

News Details Young healthy subjects and patients with systemic lupus erythematosus (SLE). NR reduced relative mRNA expressions of inflammatory cytokines ...

4. cc.nih.gov cc.nih.gov/recruit/protocols/001621-H

Double-Blind Placebo Controlled Study to Evaluate the ... A dietary supplement called nicotinamide riboside (NR) decreases some markers of inflammation in the blood and will research the connection between immune cell ...

5. withpower.com withpower.com/trial/phase-2-lupus-erythematosus-systemic-8-2023-8e70d

Nicotinamide Riboside for Systemic Lupus Erythematosus ... Trial Overview The trial tests if Nicotinamide Riboside (NR) can improve immune system metabolism in SLE by boosting NAD+ levels. It compares NR's effects on ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10361580/

What is really known about the effects of nicotinamide ... Nicotinamide riboside may play a role in the reduction of inflammatory states and has shown some potential in the treatment of diverse severe diseases.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10459282/

Nicotinamide Riboside, a Promising Vitamin B3 Derivative for ... Among the NAD+ precursors, NR may be preferred, as it produces fewer reported unfavorable side effects [7]. In its classical metabolic roles, NAD+ is a ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/acel.70093

Nicotinamide Riboside Supplementation Benefits in ... The exploratory endpoints involved metabolome profiles of plasma. No serious adverse events were observed during NR treatment. Importantly, CAVI ...

9. facebook.com facebook.com/NIHClinicalCenter/posts/people-with-systemic-lupus-erythematosus-sle-are-at-risk-of-developing-inflammat/1124891569682151/

People with systemic lupus erythematosus (SLE) are at risk ... A research study at NIH is testing if the dietary supplement, Nicotinamide Riboside (NR), can improve immune system and blood vessel function and inflammation ...

10. jci.org jci.org/articles/view/139828

Boosting NAD + blunts TLR4-induced type I IFN in control ... Safety and metabolism of long-term administration of NIAGEN (nicotinamide riboside chloride) in a randomized, double-blind, placebo ...