Treatment of Systemic Lupus Erythematosus (SLE) With N-acetylcysteine
NCT ID: NCT00775476
Last Updated: 2024-11-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
290 participants
INTERVENTIONAL
2022-05-05
2028-09-30
Brief Summary
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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.
Detailed Description
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The primary outcome variable will be the response (yes/no) in the SLE Respinder Index or SRI at Month 12 (reduction ≥ 4 points in SELENA-SLEDAI score and therefore also called SRI-4; no new BILAG A organ domain score and no more than 1 new BILAG B organ domain score; and no worsening in Physician's Global Assessment (PGA) score) by ≥ 0.3 points versus baseline). A positive response will also require no treatment failure, defined as the need for non-protocol treatment, i.e., new or increased immunosuppressives or antimalarials; increased or parenteral corticosteroids; or premature discontinuation from study treatment. Corticosteroids can be tapered off at the investigator's discretion, based on disease activity. Four weeks after randomization, once tapered, corticosteroids can only be increased again to the dosage preceding the last taper step; any larger increase will be deemed a treatment failure. In addition, any increase in corticosteroid dosage during the last 3 months of the trial will result in declaration of treatment failure.
We will monitor tolerance and safety, and assess SLEDAI, BILAG, FAS, PROMIS, ASRS, prednisone use, liver and bone marrow function as secondary outcomes.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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NAC
2.4 g - 4.8 g of NAC daily starting after 3 month open label titration period.
N-acetylcysteine
Capsules of NAC, each containing 600 mg of NAC between dosages of 2.4 g to 4.8 g daily
Placebo
2.4 g - 4.8 g of placebo per day after 3 month open label titration period.
Placebo
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.
Interventions
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N-acetylcysteine
Capsules of NAC, each containing 600 mg of NAC between dosages of 2.4 g to 4.8 g daily
Placebo
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.
Eligibility Criteria
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Inclusion Criteria
* 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;
* 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.
Exclusion Criteria
* 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 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.
18 Years
ALL
Yes
Sponsors
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Cedars-Sinai Medical Center
OTHER
University of Rochester
OTHER
Yale University
OTHER
Penn State University
OTHER
Hospital for Special Surgery, New York
OTHER
Ohio State University
OTHER
Oklahoma City VA Health Care System
FED
St. Luke's Hospital and Health Network, Pennsylvania
OTHER
State University of New York - Upstate Medical University
OTHER
Responsible Party
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Principal Investigators
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Andras Perl, M.D., Ph.D.
Role: PRINCIPAL_INVESTIGATOR
State University of New York - Upstate Medical University
Locations
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Cedars-Sinai Medical Center
Los Angeles, California, United States
Yale Center for Clinical Investigation
New Haven, Connecticut, United States
Hospital for Special Surgery
New York, New York, United States
SUNY Upstate Medical University
Syracuse, New York, United States
The Ohio State University
Columbus, Ohio, United States
VA Medical Center
Oklahoma City, Oklahoma, United States
St. Luke's University Health Network
Allentown, Pennsylvania, United States
Penn State MS Hershey Medical Center
Hershey, Pennsylvania, United States
Countries
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Central Contacts
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Facility Contacts
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References
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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.
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.
Other Identifiers
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NIH Award #1U01AR076092 - 01A1
Identifier Type: -
Identifier Source: secondary_id
IRBnet # 1566736
Identifier Type: -
Identifier Source: org_study_id