N-acetylcysteine for Primary Sjögren's Syndrome (NACSS)

University of Sao Paulo General Hospital

Status

Completed

Conditions

Sicca Syndrome

Sjögren Syndrome

Treatments

Drug: Placebo syrup

Drug: N-acetylcysteine syrup

Study type

Interventional

Funder types

Other

Identifiers

NCT04793646

24088719.4.0000.0068

Details and patient eligibility

About

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.

Full 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.

Enrollment

60 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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.

Exclusion criteria

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.