N-acetylcysteine for Primary Sjögren's Syndrome

Study Overview
=================
Brief 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. 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.

Official Title
-----------------
Prospective Randomized, Double-blind Controlled Clinical Study of N-acetylcysteine for Treatment of Dryness Symptoms Due to Primary Sjogren's Syndrome

Conditions
-----------------
Sjögren Syndrome, Sicca Syndrome

Intervention / Treatment
-----------------
* Drug: N-acetylcysteine syrup
* Drug: Placebo syrup


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind controlled study of N-acetylcysteine for treatment of dryness symptoms due to primary Sjogren's syndrome
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: N-acetylcysteine syrup<br>Thirty pSS patients | Drug: N-acetylcysteine syrup<br>* N-acetylcysteine syrup 600 mg (15 mL) twice a day for 3 months<br>* Other names: N-acetylcysteine;|
| Placebo Comparator: Placebo syrup<br>Thirty pSS patients | Drug: Placebo syrup<br>* Placebo syrup 15 mL twice a day for 3 months<br>* Other names: Placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) | Comparative analysis of ESSPRI values | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Xerostomia inventory | Comparative analysis of xerostomia inventory values | 3 months |