Sjögren SyndromeNACSSNCT04793646
N-acetylcysteine for Primary Sjögren's Syndrome
A study testing N-acetylcysteine syrup in people with Sjögren Syndrome and Sicca Syndrome, run by University of Sao Paulo General Hospital at 2 sites in Brazil.
Trial summary
N-acetylcysteine (NAC) allows the elimination of reactive oxygen species (ROSs) and it has an anti-inflammatory effect. For this reason, NAC has been used and researched for treatment of several diseases, such as autoimmune diseases. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Sjögren Syndrome, Sicca Syndrome
- What is being tested?
- N-acetylcysteine syrup
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 2 sitesBrazil
- Study dates
- 30 Apr 2021to 21 Jan 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Agreement to participate in the study according to signed informed consent.
- Filling the pSS classification criteria.
- Absence of other autoimmune associates systemic diseases.
- EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) <= 5.
- Prednisone dose < 20 mg/day at study inclusion.
- Without pilocarpine or cevimeline use at study inclusion.
- No use of N-acetylcysteine for at least 1 month before study inclusion.
Who cannot join
- Diabetes, sarcoidosis, previous history of head and neck radiotherapy or iodine therapy, positive serologies for HIV, hepatitis B and C, graft versus host disease, IgG4 (immunoglobulin G4) related disease, and current use of antidepressants tricyclics.
- Current use of biological therapy.
- Current smoking.
- Alcoholism.
- Liver cirrhosis and chronic kidney disease.
Trial locations and contacts
2 sites in 1 country.
Brazil2 sites
Hospital das Clinicas da Faculdade de Medicina da USP
São Paulo, São Paulo, 05403-000
Rheumatology Division of Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo
São Paulo, São Paulo, 05403-000
About this study
Official title: Prospective Randomized, Double-blind Controlled Clinical Study of N-acetylcysteine for Treatment of Dryness Symptoms Due to Primary Sjogren's Syndrome
N-acetylcysteine (NAC) allows the elimination of reactive oxygen species (ROSs) and it has an anti-inflammatory effect. For this reason, NAC has been used and researched for treatment of several diseases, such as autoimmune diseases. In these diseases there are a process of oxidative stress due to chronic inflammation, which promotes an imbalance between ROSs levels and the cellular capacity to eliminate reactive intermediates and repair the resulting damage through antioxidants. The imbalance between the production of free radicals from oxygen and antioxidant species may also be involved in the pathogenesis of primary Sjögren's syndrome (pSS). In fact, increased levels of oxidative stress markers were detected in biopsy samples from minor salivary glands in these patients. Treatment of pSS is not well established and it is also not able to modify the evolution of the disease, being often only symptomatic. In addition, there is little data in the literature regarding the true efficacy of NAC in the treatment of pSS and the few existing studies have evaluated heterogeneous populations (including patients with other causes of sicca syndrome) and validated instruments to measure the symptom index and disease activity were not use in these previous studies. Thus, the present randomized double-blind clinical study aims to evaluate the efficacy of NAC in the control of sicca syndrome symptoms in a homogeneous population of patients with pSS (not only regarding the classification criteria, but also regarding the low rate of systemic disease activity at study inclusion) through tests widely accepted in the literature. Additionally, the investigators will study the possible role of NAC on oxidative stress in peripheral blood and saliva of these patients.
Read the detailed description
Study design: This is a prospective, randomized, double-blind controlled study of N-acetylcysteine (600 mg orally every 12 hours in the form of syrup) lasting 12 weeks for the treatment of sicca syndrome symptoms due to pSS.
Patients: Sixty adult female patients (aged >=18 years), with a well-established diagnosis of pSS (2016 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) and/or 2002 American-European Consensus classification criteria) and follow-up regularly at the Sjögren Syndrome Outpatient Clinic of the Rheumatology Division of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP).
Sample size: There is only a controlled study of NAC for treatment of SS, which included a heterogeneous population with a total of 26 patients and who observed superiority to placebo in the sicca symptoms control. Based on this study, the investigators will work with a convenience sample of 60 patients.
Clinical evaluation: It will be carried out at study inclusion, 4 weeks and 12 weeks through clinical instruments widely accepted in the literature.
Laboratorial evaluation: ROs will also be assessed throughout the study.
- Conditions
- Sjögren Syndrome, Sicca Syndrome
- Being tested
- N-acetylcysteine syrup, Placebo syrup
- Medical subject headings
- Sjogren's Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteine syrupDrug
Also called N-acetylcysteine
N-acetylcysteine syrup 600 mg (15 mL) twice a day for 3 months
Placebo syrupDrug
Also called Placebo
Placebo syrup 15 mL twice a day for 3 months
| Study group | Role | What they receive |
|---|---|---|
| N-acetylcysteine syrup | Active comparator | Thirty pSS patients Receives: Drug: N-acetylcysteine syrup |
| Placebo syrup | Placebo comparator | Thirty pSS patients Receives: Drug: Placebo syrup |
What is being measured
The primary outcome is the main question the study is designed to answer.
EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI)
Comparative analysis of ESSPRI values
Measured: 3 months
Secondary outcomes (1)
Xerostomia inventory
Comparative analysis of xerostomia inventory values
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2021
- Study start30 Apr 2021
- Primary completion31 Dec 2024
- Study completion21 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Sjögren SyndromeStudies of the same condition, open and under way.
- More trials run by University of Sao Paulo General HospitalThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double-blind controlled study of N-acetylcysteine for treatment of dryness symptoms due to primary Sjogren's syndrome
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sandra Pasoto, MD, PhD, Principal investigator, University of Sao Paulo General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04793646
- Sponsor's protocol ID
- 24088719.4.0000.0068
- Acronym
- NACSS
- Status last verified
- Jan 2025
- First submitted
- 8 Mar 2021
- Last updated
- 27 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH; European Study Group on Classification Criteria for Sjogren's Syndrome. Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002 Jun;61(6):554-8. doi: 10.1136/ard.61.6.554.
PubMed 12006334Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, Rasmussen A, Scofield H, Vitali C, Bowman SJ, Mariette X; International Sjogren's Syndrome Criteria Working Group. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjogren's syndrome: A consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis. 2017 Jan;76(1):9-16. doi: 10.1136/annrheumdis-2016-210571. Epub 2016 Oct 26.
PubMed 27789466Seror R, Ravaud P, Mariette X, Bootsma H, Theander E, Hansen A, Ramos-Casals M, Dorner T, Bombardieri S, Hachulla E, Brun JG, Kruize AA, Praprotnik S, Tomsic M, Gottenberg JE, Devauchelle V, Devita S, Vollenweider C, Mandl T, Tzioufas A, Carsons S, Saraux A, Sutcliffe N, Vitali C, Bowman SJ; EULAR Sjogren's Task Force. EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjogren's syndrome. Ann Rheum Dis. 2011 Jun;70(6):968-72. doi: 10.1136/ard.2010.143743. Epub 2011 Feb 22.
PubMed 21345815Seror R, Ravaud P, Bowman SJ, Baron G, Tzioufas A, Theander E, Gottenberg JE, Bootsma H, Mariette X, Vitali C; EULAR Sjogren's Task Force. EULAR Sjogren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren's syndrome. Ann Rheum Dis. 2010 Jun;69(6):1103-9. doi: 10.1136/ard.2009.110619. Epub 2009 Jun 28.
PubMed 19561361Walters MT, Rubin CE, Keightley SJ, Ward CD, Cawley MI. A double-blind, cross-over, study of oral N-acetylcysteine in Sjogren's syndrome. Scand J Rheumatol Suppl. 1986;61:253-8.
PubMed 3296153Ramos-Casals M, Brito-Zeron P, Siso-Almirall A, Bosch X. Primary Sjogren syndrome. BMJ. 2012 Jun 14;344:e3821. doi: 10.1136/bmj.e3821. No abstract available.
PubMed 22700787Danilovic A, Lucon AM, Srougi M, Shimizu MH, Ianhez LE, Nahas WC, Seguro AC. Protective effect of N-acetylcysteine on early outcomes of deceased renal transplantation. Transplant Proc. 2011 Jun;43(5):1443-9. doi: 10.1016/j.transproceed.2011.02.020.
PubMed 21693215D'Agostino Gennari J, Deveza GBH, Ribeiro CT, Seguro AC, Aikawa NE, Shimizu MHM, Leon EP, Guedes LKN, Kupa LVK, Silva CAA, Bonfa E, Pasoto SG. Efficacy of N-acetylcysteine for treating dryness symptoms of Sjogren's disease: randomised placebo-controlled double-blind clinical study. Clin Exp Rheumatol. 2024 Dec;42(12):2427-2436. doi: 10.55563/clinexprheumatol/dmd5dv. Epub 2024 Sep 27.
PubMed 39360368
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Randomized, Double-blind Controlled Clinical Study of N-acetylcysteine for Treatment of Dryness Symptoms Due to Primary Sjogren's Syndrome
- ClinicalTrials.gov ID
- NCT04793646
- Acronym / sponsor ID
- NACSS / 24088719.4.0000.0068
- Conditions
- Sjögren Syndrome, Sicca Syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of Sao Paulo General HospitalUniversity, hospital or other
- Study start
- 30 Apr 2021 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 21 Jan 2025 (actual)
- First posted
- 11 Mar 2021 (actual)
- 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.
N-acetylcysteine (NAC) allows the elimination of reactive oxygen species (ROSs) and it has an anti-inflammatory effect. For this reason, NAC has been used and researched for treatment of several diseases, such as autoimmune diseases. In these diseases there are a process of oxidative stress due to chronic inflammation, which promotes an imbalance between ROSs levels and the cellular capacity to eliminate reactive intermediates and repair the resulting damage through antioxidants. The imbalance between the production of free radicals from oxygen and antioxidant species may also be involved in the pathogenesis of primary Sjögren's syndrome (pSS). In fact, increased levels of oxidative stress markers were detected in biopsy samples from minor salivary glands in these patients. Treatment of pSS is not well established and it is also not able to modify the evolution of the disease, being often only symptomatic. In addition, there is little data in the literature regarding the true efficacy of NAC in the treatment of pSS and the few existing studies have evaluated heterogeneous populations (including patients with other causes of sicca syndrome) and validated instruments to measure the symptom index and disease activity were not use in these previous studies. Thus, the present randomized double-blind clinical study aims to evaluate the efficacy of NAC in the control of sicca syndrome symptoms in a homogeneous population of patients with pSS (not only regarding the classification criteria, but also regarding the low rate of systemic disease activity at study inclusion) through tests widely accepted in the literature. Additionally, the investigators will study the possible role of NAC on oxidative stress in peripheral blood and saliva of these patients.
Detailed description
Study design: This is a prospective, randomized, double-blind controlled study of N-acetylcysteine (600 mg orally every 12 hours in the form of syrup) lasting 12 weeks for the treatment of sicca syndrome symptoms due to pSS.
Patients: Sixty adult female patients (aged >=18 years), with a well-established diagnosis of pSS (2016 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) and/or 2002 American-European Consensus classification criteria) and follow-up regularly at the Sjögren Syndrome Outpatient Clinic of the Rheumatology Division of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP).
Sample size: There is only a controlled study of NAC for treatment of SS, which included a heterogeneous population with a total of 26 patients and who observed superiority to placebo in the sicca symptoms control. Based on this study, the investigators will work with a convenience sample of 60 patients.
Clinical evaluation: It will be carried out at study inclusion, 4 weeks and 12 weeks through clinical instruments widely accepted in the literature.
Laboratorial evaluation: ROs will also be assessed throughout the study.
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
- Randomized, double-blind controlled study of N-acetylcysteine for treatment of dryness symptoms due to primary Sjogren's syndrome
| Arm | Type | Receives |
|---|---|---|
| N-acetylcysteine syrup | Active comparator | Drug: N-acetylcysteine syrupThirty pSS patients |
| Placebo syrup | Placebo comparator | Drug: Placebo syrupThirty pSS patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Agreement to participate in the study according to signed informed consent.
- Filling the pSS classification criteria.
- Absence of other autoimmune associates systemic diseases.
- EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) <= 5.
- Prednisone dose < 20 mg/day at study inclusion.
Key exclusion criteria (5 listed)
- Diabetes, sarcoidosis, previous history of head and neck radiotherapy or iodine therapy, positive serologies for HIV, hepatitis B and C, graft versus host disease, IgG4 (immunoglobulin G4) related disease, and current use of antidepressants tricyclics.
- Current use of biological therapy.
- Current smoking.
- Alcoholism.
- Liver cirrhosis and chronic kidney disease.
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-acetylcysteine syrupAlso: N-acetylcysteineN-acetylcysteine syrup 600 mg (15 mL) twice a day for 3 months | Drug | N-acetylcysteine syrup |
| Placebo syrupAlso: PlaceboPlacebo syrup 15 mL twice a day for 3 months | Drug | Placebo syrup |
Primary outcome
EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI)
Time frame: 3 months
Comparative analysis of ESSPRI values
1 secondary outcome
Xerostomia inventory
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2025.
- Background: PubMed 12006334Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH; European Study Group on Classification Criteria for Sjogren's Syndrome. Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002 Jun;61(6):554-8. doi: 10.1136/ard.61.6.554.
- Background: PubMed 27789466Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, Rasmussen A, Scofield H, Vitali C, Bowman SJ, Mariette X; International Sjogren's Syndrome Criteria Working Group. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjogren's syndrome: A consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis. 2017 Jan;76(1):9-16. doi: 10.1136/annrheumdis-2016-210571. Epub 2016 Oct 26.
- Background: PubMed 21345815Seror R, Ravaud P, Mariette X, Bootsma H, Theander E, Hansen A, Ramos-Casals M, Dorner T, Bombardieri S, Hachulla E, Brun JG, Kruize AA, Praprotnik S, Tomsic M, Gottenberg JE, Devauchelle V, Devita S, Vollenweider C, Mandl T, Tzioufas A, Carsons S, Saraux A, Sutcliffe N, Vitali C, Bowman SJ; EULAR Sjogren's Task Force. EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjogren's syndrome. Ann Rheum Dis. 2011 Jun;70(6):968-72. doi: 10.1136/ard.2010.143743. Epub 2011 Feb 22.
- Background: PubMed 19561361Seror R, Ravaud P, Bowman SJ, Baron G, Tzioufas A, Theander E, Gottenberg JE, Bootsma H, Mariette X, Vitali C; EULAR Sjogren's Task Force. EULAR Sjogren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren's syndrome. Ann Rheum Dis. 2010 Jun;69(6):1103-9. doi: 10.1136/ard.2009.110619. Epub 2009 Jun 28.
- Background: PubMed 3296153Walters MT, Rubin CE, Keightley SJ, Ward CD, Cawley MI. A double-blind, cross-over, study of oral N-acetylcysteine in Sjogren's syndrome. Scand J Rheumatol Suppl. 1986;61:253-8.
- Background: PubMed 22700787Ramos-Casals M, Brito-Zeron P, Siso-Almirall A, Bosch X. Primary Sjogren syndrome. BMJ. 2012 Jun 14;344:e3821. doi: 10.1136/bmj.e3821. No abstract available.
- Background: PubMed 21693215Danilovic A, Lucon AM, Srougi M, Shimizu MH, Ianhez LE, Nahas WC, Seguro AC. Protective effect of N-acetylcysteine on early outcomes of deceased renal transplantation. Transplant Proc. 2011 Jun;43(5):1443-9. doi: 10.1016/j.transproceed.2011.02.020.
- Derived from this study: PubMed 39360368D'Agostino Gennari J, Deveza GBH, Ribeiro CT, Seguro AC, Aikawa NE, Shimizu MHM, Leon EP, Guedes LKN, Kupa LVK, Silva CAA, Bonfa E, Pasoto SG. Efficacy of N-acetylcysteine for treating dryness symptoms of Sjogren's disease: randomised placebo-controlled double-blind clinical study. Clin Exp Rheumatol. 2024 Dec;42(12):2427-2436. doi: 10.55563/clinexprheumatol/dmd5dv. Epub 2024 Sep 27.
- Individual participant dataSharing planned: No
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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.
Sandra Pasoto, MD, PhD principal investigator
University of Sao Paulo General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing N-acetylcysteine syrup in people with Sjögren Syndrome and Sicca Syndrome, run by University of Sao Paulo General Hospital at 2 sites in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. 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: finished, as of the sponsor's last update on 27 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Brazil. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) (time frame: 3 months). 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 NCT04793646, which also lists 8 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 27 Jan 2025.