Treatment of Systemic Lupus Erythematosus (SLE) With N-acetylcysteine

NCT00775476 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRBnet # 1566736NIH Award #1U01AR076092 - 01A1
• Study Type: interventional
• Target: 290
• Locations: 1 country
• Sites: 12

Brief Summary

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease which often has debilitating and potentially life-threatening consequences. The cause of SLE is unknown and current therapies lack specificity and carry significant side-effects. We previously discovered the depletion of glutathione in lymphocytes of patients with SLE and associated this metabolic change with the elevation of the mitochondrial transmembrane potential. This study will titrate to tolerance during an initial 3 month open label period and then subjects will be randomized to one of 2 arms. It was determined by statistical analysis that each group must have 105 subjects. All subjects will be enrolled and evaluated for tolerance of NAC between dosages of 2.4 g/day and 4.8 g/day for 3 months. After A 3-month open-label dose-titration phase, SLE subjects will be randomized into 2 groups of 105 subjects either to continue the tolerated dosage of NAC or switched to equal number of placebo capsules. There will be up to seven study visits per SLE subject, including the screening and wash out visits. Visits 2-6 will be scheduled three months apart. The study will last 13 months with the wash-out visit. Each subject will donate approximately 100 ml of blood for biomarker studies at each visit. Healthy control subjects will donate blood at the same time. They will be matched to the SLE subjects by gender, age within 10 years, and ethnicity. Their blood will be used as reference for biomarker assays. There is a consent form required to participate in the phase II study.

Conditions

Systemic Lupus Erythematosus

Keywords

Systemic lupus erythematosus (SLE), an autoimmune disease

Outcome Measures

Primary Outcomes (3)

• Therapeutic benefit

  Positive response on the SLE Responder Index (SRI) in the NAC arm vs placebo

  12 months

• Improvement of disease activity

  Improvement of disease activity as measurable by the reduction of SLEDAI or BILAG disease activity scores and the reduction of prednisone usage

  12 months

• Tolerance and safety

  Monitor adverse events and tolerance of the study drug

  12 months

Secondary Outcomes (1)

• Immunobiological outcomes measurable improved lymphocyte function

  12 months

Study Arms (2)

NAC

ACTIVE COMPARATOR

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

Drug: N-acetylcysteine

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

N-acetylcysteine DRUG

Capsules of NAC, each containing 600 mg of NAC between dosages of 2.4 g to 4.8 g daily

NAC

Placebo DRUG

placebo (sugar) twice daily, daily dosage will match that of NAC that was tolerated between daily dosages of 2.4 g and 4.8 g during the open-label titration phase.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18;
• Male or female;
• ≥ 4 ACR SLE classification criteria (104,105);
• Positive ANA at a titer of ≥ 1/80;
• Stable immunosuppressants (MMF ≤ 3 g/day, azathioprine ≤ 150 mg/day; methotrexate ≤ 25 mg/week; leflunomide ≤ 20 mg/week; cyclosporin 100 mg/day; voclosporin 47.4 mg/day) and/or antimalarials (hydroxychloroquine ≤ 400 mg/day) for 30 days prior to screening; stable oral corticosteroids for 2 weeks prior to screening; ≤ 20 mg/day prednisone or equivalent; stable belimumab or anifrolumab for 90 days prior to screening;
• Untreated patients must be off above immunosuppressants and/or antimalarials for 30 days prior to screening; oral corticosteroids for 2 weeks prior to screening; belimumab or anifrolumab for 90 days prior to screening;
• BILAG 2004 index (48) level A disease activity in ≥ 1 organ/system except renal or central nervous system or BILAG 2004 index level B disease activity in ≥ 1 organs/systems if no level A disease activity is present and SLEDAI ≥ 6 (106);
• Enrollment is approved by adjudication committee within 10 days, which may include retesting and communication with study sites, as necessary.
• Patients may be considered for enrollment 12 months after rituximab treatment, or 6 months after rituximab treatment if their B cell counts have normalized.

You may not qualify if:

• Acute SLE flare threatening vital organs;
• Pregnant or lactating;
• Moderately serious or serious comorbidities (e.g., diabetes mellitus, congestive heart failure, chronic obstructive pulmonary disease, chronic renal insufficiency) that in investigator's opinion confers high risk for adverse events;
• Patients receiving cyclophosphamide within 3 months;
• Active chronic infections (e.g., HIV, hepatitis B virus, hepatitis C virus, mycobacteria); patients 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 (which is considered sufficient time to revert GSH to pre-treatment levels (29);
• Patients who participated in the pilot RCT or are taking daily acetaminophen (≤ 1 g/day prn is allowed if documented);
• Patients receiving mTOR inhibitors (rapamycin/sirolimus, everolimus);
• Patients enrolled in other interventional trials.
• Patients should not take medications containing acetaminophen (Tylenol) as it may reduce the effectiveness of NAC. 1 g/day of acetaminophen is allowed if documented. Patients who are currently taking more than 1 gram of acetaminophen per day may be eligible for participation if they are willing to reduce their intake to 1 gram per day or less prior to enrollment.
• Patients should avoid taking more than 500 mg of vitamin C and more than 30 IU of vitamin E daily as both vitamin C and E can confound the study results. However, patients currently taking doses above these thresholds may be eligible for participation if they are willing to reduce their intake to 500 mg or less of vitamin C and 30 IU or less of vitamin E per day prior to enrollment.

Sponsors & Collaborators

• State University of New York - Upstate Medical University: lead
• Cedars-Sinai Medical Center: collaborator
• Penn State University: collaborator
• Columbia University: collaborator
• Hospital for Special Surgery, New York: collaborator
• Yale University: collaborator
• Ohio State University: collaborator
• Oklahoma City VA Health Care System: collaborator
• St. Luke's Hospital and Health Network, Pennsylvania: collaborator
• Emory University: collaborator
• University of Pittsburgh: collaborator
• University of Kentucky: collaborator
• University of Rochester: collaborator

Study Sites (12)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Yale Center for Clinical Investigation

New Haven, Connecticut, 06519, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30307, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

University of Columbia

New York, New York, 10032, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

VA Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

St. Luke's University Health Network

Allentown, Pennsylvania, 18102, United States

Location

Penn State MS Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

Related Publications (2)

• Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.

  PMID: 33687069 DERIVED

• Lai ZW, Hanczko R, Bonilla E, Caza TN, Clair B, Bartos A, Miklossy G, Jimah J, Doherty E, Tily H, Francis L, Garcia R, Dawood M, Yu J, Ramos I, Coman I, Faraone SV, Phillips PE, Perl A. N-acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2012 Sep;64(9):2937-46. doi: 10.1002/art.34502.

  PMID: 22549432 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Andras Perl, M.D., Ph.D.

  State University of New York - Upstate Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study will titrate to tolerance during an initial 3 month open label period and then subjects will be randomized to one of 2 arms.

Study Record Dates

• First Submitted: October 17, 2008
• First Posted: October 20, 2008
• Study Start: May 5, 2022
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): September 30, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (12)