Systemic Lupus ErythematosusPhase 2NACNCT00775476
Treatment of Systemic Lupus Erythematosus (SLE) With N-acetylcysteine
A Phase 2 study testing N-acetylcysteine in people with Systemic Lupus Erythematosus, run by State University of New York - Upstate Medical University at 12 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Systemic Lupus Erythematosus
- What is being tested?
- N-acetylcysteine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 290 participants
- Where
- 12 sitesUnited States
- Study dates
- 5 May 2022to 30 Sep 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Participant Inclusion Criteria
- 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.
Participant Exclusion Criteria
- 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.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
St. Luke's University Health Network
Allentown, Pennsylvania, 18102
Emory University School of Medicine
Atlanta, Georgia, 30307
The Ohio State University
Columbus, Ohio, 43210
Penn State MS Hershey Medical Center
Hershey, Pennsylvania, 17033
University of Kentucky
Lexington, Kentucky, 40536
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Yale Center for Clinical Investigation
New Haven, Connecticut, 06519
Hospital for Special Surgery
New York, New York, 10021
University of Columbia
New York, New York, 10032
VA Medical Center
Oklahoma City, Oklahoma, 73104
University of Pittsburgh
Pittsburgh, Pennsylvania, 15261
SUNY Upstate Medical University
Syracuse, New York, 13210
About this study
Official title: Treatment of Systemic Lupus Erythematosus (SLE) With N-acetylcysteine (NAC) (SNAC)
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.
Read more
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.
Read the detailed description
Subjects will take NAC in a dose range of 2.4 g/day to 4.8 g/day which will be titrated to tolerance during an initial 3-month open label period. After the 3-month open label period, patients in each arm will continue taking equal numbers of capsules representing a dosage that has been titrated to tolerance. 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/day dextrose) capsules twice daily for the 9 subsequent months.
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
- Systemic Lupus Erythematosus
- Being tested
- N-acetylcysteine, Placebo
- Keywords
- Systemic lupus erythematosus (SLE), an autoimmune disease
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
Capsules of NAC, each containing 600 mg of NAC between dosages of 2.4 g to 4.8 g daily
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| NAC | Active comparator | 2.4 g - 4.8 g of NAC daily starting after 3 month open label titration period. Receives: Drug: N-acetylcysteine |
| Placebo | Placebo comparator | 2.4 g - 4.8 g of placebo per day after 3 month open label titration period. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Therapeutic benefit
Positive response on the SLE Responder Index (SRI) in the NAC arm vs placebo
Measured: 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
Measured: 12 months
Tolerance and safety
Monitor adverse events and tolerance of the study drug
Measured: 12 months
Secondary outcomes (1)
Immunobiological outcomes measurable improved lymphocyte function
Immunobiological outcomes measurable by improved markers of glutathioen depletion, mitochondrial function and activation of T and B lymphocytes
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2008 (estimated)
- Study start5 May 2022
- Primary completion31 Mar 2027 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 290 participants (estimated)
Sponsor and investigators
- Lead sponsor
- State University of New York - Upstate Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Cedars-Sinai Medical Center, Penn State University, Columbia University, Hospital for Special Surgery, New York, Yale University, Ohio State University, Oklahoma City VA Health Care System, St. Luke's Hospital and Health Network, Pennsylvania, Emory University, University of Pittsburgh, University of Kentucky, University of Rochester
- Responsible party
- Sponsor
- Investigators
- Andras Perl, M.D., Ph.D., Principal investigator, State University of New York - Upstate Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00775476
- Sponsor's protocol ID
- IRBnet # 1566736
- Other IDs
- NIH Award #1U01AR076092 - 01A1
- Acronym
- NAC
- Status last verified
- Apr 2026
- First submitted
- 17 Oct 2008
- Last updated
- 24 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 33687069Lai 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.
PubMed 22549432
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Systemic Lupus Erythematosus (SLE) With N-acetylcysteine (NAC) (SNAC)
- ClinicalTrials.gov ID
- NCT00775476
- Acronym / sponsor ID
- NAC / IRBnet # 1566736
- Conditions
- Systemic Lupus Erythematosus
- Keywords
- Systemic lupus erythematosus (SLE), an autoimmune disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 290 participants (estimated)
- Lead sponsor
- State University of New York - Upstate Medical UniversityUniversity, hospital or other
- Collaborators
- Cedars-Sinai Medical Center, Penn State University, Columbia University, Hospital for Special Surgery, New York, Yale University, Ohio State University, Oklahoma City VA Health Care System, St. Luke's Hospital and Health Network, Pennsylvania, Emory University, University of Pittsburgh, University of Kentucky, University of Rochester
- Study start
- 5 May 2022 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 30 Sep 2028 (estimated)
- First posted
- 20 Oct 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Subjects will take NAC in a dose range of 2.4 g/day to 4.8 g/day which will be titrated to tolerance during an initial 3-month open label period. After the 3-month open label period, patients in each arm will continue taking equal numbers of capsules representing a dosage that has been titrated to tolerance. 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/day dextrose) capsules twice daily for the 9 subsequent months.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| NAC | Active comparator | Drug: N-acetylcysteine2.4 g - 4.8 g of NAC daily starting after 3 month open label titration period. |
| Placebo | Placebo comparator | Drug: Placebo2.4 g - 4.8 g of placebo per day after 3 month open label titration period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetylcysteineCapsules of NAC, each containing 600 mg of NAC between dosages of 2.4 g to 4.8 g daily | Drug | NAC |
| Placeboplacebo (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. | Drug | Placebo |
Primary outcome
Therapeutic benefit
Time frame: 12 months
Positive response on the SLE Responder Index (SRI) in the NAC arm vs placebo
Improvement of disease activity
Time frame: 12 months
Improvement of disease activity as measurable by the reduction of SLEDAI or BILAG disease activity scores and the reduction of prednisone usage
Tolerance and safety
Time frame: 12 months
Monitor adverse events and tolerance of the study drug
1 secondary outcome
Immunobiological outcomes measurable improved lymphocyte function
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2026.
- Derived from this study: PubMed 33687069Hannon 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.
- Derived from this study: PubMed 22549432Lai 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andras Perl, M.D., Ph.D. principal investigator
State University of New York - Upstate Medical University
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing N-acetylcysteine in people with Systemic Lupus Erythematosus, run by State University of New York - Upstate Medical University at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Therapeutic benefit (time frame: 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00775476, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2026.