N-acetylcysteine for Lupus

(NAC Trial)

Recruiting at 7 trial locations

Overseen By Kyriakos Kirou, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: State University of New York - Upstate Medical University

Must be taking: Immunosuppressants, Antimalarials, Corticosteroids

Must not be taking: Cyclophosphamide, mTOR inhibitors, Antioxidants

Disqualifiers: Acute SLE flare, Pregnancy, Serious comorbidities, Active infections, others

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 8

290 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests N-acetylcysteine (NAC) as a treatment for systemic lupus erythematosus (SLE), a chronic disease that causes inflammation and can be life-threatening. Researchers aim to determine if NAC can manage SLE symptoms without the harsh side effects of current treatments. Participants will take NAC for three months to establish a safe dose, then be randomly assigned to continue with NAC or switch to a placebo. Suitable candidates have SLE, confirmed by a positive ANA test, and have been stable on certain medications for a while. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications if they are stable immunosuppressants, antimalarials, or oral corticosteroids, as long as they meet specific dosage limits. However, you must stop taking NAC or other antioxidants at least one month before screening, and avoid certain vitamins and medications like high doses of vitamin C, vitamin E, and acetaminophen.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that N-acetylcysteine (NAC) is generally safe for people with lupus. In studies, patients took up to 4.8 grams a day without major side effects. One study found that taking 1.8 grams a day for three months caused no harmful effects.

Another study found that NAC not only improved lupus symptoms but was also well-tolerated at doses of 2.4 grams and 4.8 grams per day. These findings suggest that NAC is a safe option for people with lupus, based on past research. ^{1 2 3 4 5}

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

Unlike most treatments for lupus that focus on suppressing the immune system, N-acetylcysteine (NAC) offers a different approach by acting as an antioxidant. NAC is unique because it helps to replenish glutathione, a powerful antioxidant in the body, potentially reducing oxidative stress, which is a key player in lupus flare-ups. Researchers are excited about NAC because it could complement existing therapies like corticosteroids and immunosuppressants, potentially offering a gentler option with fewer side effects.

What evidence suggests that N-acetylcysteine might be an effective treatment for lupus?

Research has shown that N-acetylcysteine (NAC) can help treat systemic lupus erythematosus (SLE). Studies have found that taking 1800 mg of NAC daily can reduce disease activity and complications. In this trial, participants will receive either NAC or a placebo. Higher doses, such as 2.4 g/day and 4.8 g/day, have improved symptoms like disease activity and fatigue. These doses are safe and can enhance blood vessel function. Overall, NAC presents a promising option for managing SLE symptoms. ^{3 4 5 6 7}

Who Is on the Research Team?

Andras Perl, M.D., Ph.D.

Principal Investigator

State University of New York - Upstate Medical University

Are You a Good Fit for This Trial?

Adults over 18 with active Systemic Lupus Erythematosus (SLE) can join this trial. They should have a certain level of disease activity but not in the kidneys or central nervous system, and be on stable medication doses for SLE. People who are pregnant, breastfeeding, recently in other trials, or have serious health issues like heart failure cannot participate.

Inclusion Criteria

I have been diagnosed with lupus and meet at least 4 of the criteria set by the American College of Rheumatology.

I've been on stable doses of certain medications for my condition and my disease activity meets specific criteria.

I am older than 18 years.

Exclusion Criteria

I am currently taking mTOR inhibitors for my condition.

I am taking no more than 1g of acetaminophen daily or participated in the pilot RCT.

Active chronic infections (e.g., HIV, hepatitis B virus, hepatitis C virus, mycobacteria); patient with oral steroid-dependent asthma; Infections requiring intravenous antibiotics within a month or oral antibiotics within two weeks of screening; Patients taking (unwilling or unable to stop) NAC or other antioxidants within 1 month of screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Open-label Titration

Participants receive NAC in a dose range of 2.4 g/day to 4.8 g/day, titrated to tolerance

3 months

1 visit (in-person)

Randomized Treatment

Participants are randomized to continue NAC or switch to placebo, with dosage maintained

9 months

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• N-acetylcysteine
• Placebo

Trial Overview The study tests N-acetylcysteine (NAC), an antioxidant thought to help with SLE symptoms by adjusting glutathione levels. Participants will first find a tolerable dose over three months before being randomly assigned to continue NAC or switch to placebo for another ten months.

How Is the Trial Designed?

Group I: NAC Active Control 1 Intervention

2.4 g - 4.8 g of NAC daily starting after 3 month open label titration period.

Group II: Placebo Placebo Group 1 Intervention

2.4 g - 4.8 g of placebo per day after 3 month open label titration period.

N-acetylcysteine is already approved in United States, European Union for the following indications:

Approved in United States as N-acetylcysteine for:

• Acetaminophen overdose
• Chronic bronchitis
• Cystic fibrosis
• Mucolytic agent

Approved in European Union as N-acetylcysteine for:

• Paracetamol overdose
• Chronic bronchitis
• Cystic fibrosis
• Mucolytic agent

Who Is Running the Clinical Trial?

State University of New York - Upstate Medical University

Lead Sponsor

Trials

176

Recruited

27,600+

Ohio State University

Collaborator

Trials

891

Recruited

2,659,000+

St. Luke's Hospital and Health Network, Pennsylvania

Collaborator

Trials

17

Recruited

2,004,000+

Oklahoma City VA Health Care System

Collaborator

Trials

1

Recruited

290+

Cedars-Sinai Medical Center

Collaborator

Trials

523

Recruited

165,000+

Yale University

Collaborator

Trials

1,963

Recruited

3,046,000+

University of Rochester

Collaborator

Trials

883

Recruited

555,000+

Hospital for Special Surgery, New York

Collaborator

Trials

257

Recruited

61,800+

Penn State University

Collaborator

Trials

380

Recruited

131,000+

Published Research Related to This Trial

In a randomized, double-blind trial involving 80 patients with systemic lupus erythematosus (SLE), N-acetylcysteine (NAC) at 1800 mg/day for 3 months significantly reduced disease activity, as shown by lower scores on the British Isles Lupus Assessment Group (BILAG) and SLE Disease Activity Index (SLEDAI).

The NAC treatment led to improvements across various organ systems affected by SLE, with no reported adverse events, suggesting it is a safe and effective adjunct therapy for managing SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of N-acetylcysteine on systemic lupus erythematosus disease activity and its associated complications: a randomized double-blind clinical trial study. Abbasifard, M., Khorramdelazad, H., Rostamian, A., et al.[2023]

A 46-year-old patient with lupus nephritis showed improved health markers after taking 1800 mg of N-acetylcysteine (NAC), including increased glutathione levels and normalized malondialdehyde levels, indicating reduced oxidative stress.

The patient's urinary protein levels and overall health also improved, suggesting that NAC may enhance standard lupus treatment, but further well-controlled trials are necessary to confirm its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of high dose of N-acetylcysteine in lupus nephritis: a case report and literature review. Tewthanom, K., Janwitayanujit, S., Totemchockcyakarn, K., et al.[2013]

In a study of 32 patients with systemic lupus erythematosus (SLE), both N-acetylcysteine (NAC) and atorvastatin significantly improved endothelial dysfunction, as indicated by reductions in stiffness index and reflection index after treatment.

NAC treatment also led to a notable decrease in inflammatory markers (C-reactive protein and malondialdehyde), suggesting it not only improves endothelial function but also reduces oxidative stress in SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in endothelial dysfunction in patients with systemic lupus erythematosus with N-acetylcysteine and atorvastatin. Kudaravalli, J.[2022]

In a study using female B/W mice as a model for systemic lupus erythematosus (SLE), the antioxidants N-acetylcysteine (NAC) and cysteamine (CYST) significantly improved survival rates, with CYST-treated mice living an average of 48 weeks compared to 33 weeks for controls.

NAC was effective in suppressing anti-DNA antibody levels and prolonging survival, while CYST, despite increasing anti-DNA levels and causing some kidney inflammation, prevented renal insufficiency and also improved survival, suggesting that antioxidants may help manage SLE by reducing oxidative damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antioxidants suppress mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus (SLE). Suwannaroj, S., Lagoo, A., Keisler, D., et al.[2017]

In two cases of early-stage lupus nephritis, treatment with 1,200 mg of N-acetylcysteine (NAC) alongside standard therapy led to significant improvements in oxidative stress markers, including increased glutathione levels and decreased lipid peroxidation.

The addition of NAC also resulted in notable improvements in routine blood counts, urine protein levels, and overall disease activity, suggesting its potential as a beneficial adjunct treatment for lupus nephritis, although further research is needed to understand the mechanisms involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early-stage lupus nephritis treated with N-acetylcysteine: A report of two cases. Li, M., Gao, W., Ma, J., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36810107/

Effects of N-acetylcysteine on systemic lupus ... It appears that the administration of 1800 mg/day NAC to SLE patients can decrease the SLE disease activity and its complications.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00775476

Treatment of Systemic Lupus Erythematosus (SLE) With N- ... As an example, the patients tolerating 2.4 g/day, or 4 capsules containing 600 mg of NAC, after 3 months will be randomized to take 4 NAC or 4 placebo (2.4 g/ ...

3. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07083-9

Effects of N-acetylcysteine on systemic lupus erythematosus ... It appears that the administration of 1800 mg/day NAC to SLE patients can decrease the SLE disease activity and its complications.

4. grantome.com grantome.com/grant/NIH/R34-AR068052-01A1

Treatment of Systemic Lupus Erythematosus (SLE) with N- ... The results of this pilot study show that 2.4 g/day NAC and 4.8 g/day NAC are safe and they improve disease activity and fatigue through inhibiting the ...

5. journals.lww.com journals.lww.com/immunometabolism/fulltext/2022/10000/principles_behind_sle_treatment_with.2.aspx

Principles behind SLE treatment with N-acetylcysteine Improvement in endothelial dysfunction in patients with systemic lupus erythematosus with N-acetylcysteine and atorvastatin (randomized ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9605192/

Principles behind SLE treatment with N-acetylcysteine - PMC N-acetylcysteine (NAC) is an antioxidant that has shown potential benefits in SLE patients without having major side effects.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3411859/

N-ACETYLCYSTEINE REDUCES DISEASE ACTIVITY BY ... This pilot study suggests that NAC safely improves lupus disease activity by blocking mTOR in T lymphocytes. INTRODUCTION. Systemic lupus erythematosus (SLE) is ...