Effects of Probiotics on Gastrointestinal Symptoms and on the Immune System in Patients With Systemic Sclerosis

Phase 3

• Conditions: Scleroderma; Systemic Sclerosis

• Registration Number: NCT02302352
• Lead Sponsor: Federal University of São Paulo

Brief Summary

Systemic sclerosis (SSc) is an autoimmune disease with unknown etiology, which affects especially the gastrointestinal tract, lungs, heart and kidneys. Immunological abnormalities characterized by innate and acquired immune disturbances are associated with the disease development. The present study aims to evaluate the efficacy and safety of probiotics in gastrointestinal symptoms, nutritional status and innate and acquired immune responses, by means of the evaluation of IgA, Treg and Th1, Th2, and Th17 T helper subtypes levels in patients with SSc. In addition the levels of CD4+ T helper Th1, Th2 and Th17 subtypes and Treg levels will be compared to a healthy control group.

Detailed Description

Systemic sclerosis (SSc) is a chronic autoimmune disease, which affects the gastrointestinal tract, lungs, heart and kidneys. A shift in the balance between T helper 1 (Th1) and Th2 subtypes and between regulatory T cells (Treg) and Th17 cells levels, as well as intestinal microbiota abnormalities may be present in SSc. These abnormalities can stimulate inflammatory response, and cause intestinal epithelial damage. The use of oral probiotics for microbiome or immune response modulation can be attractive especially in autoimmune diseases. Objectives: To evaluate the efficacy and safety of probiotics in gastrointestinal symptoms, nutritional status and innate and acquired immune responses, by means of the evaluation of IgA, Treg and Th1, Th2, and Th17 T helper subtypes levels in patients with SSc. In addition the levels of CD4+ T helper Th1, Th2 and Th17 subtypes and Treg levels will be compared to a healthy control group. Patients and methods: A randomized double-blind placebo-controlled clinical trial, with 76 SSc patients will be performed. Patients will be randomly assigned to receive oral probiotics once a day or placebo for 8 weeks. The primary outcome will be changes in the gastrointestinal symptoms between baseline and week 8. Clinical evaluation, scleroderma Health Assessment Questionnaire (sHAQ), food intake record, anthropometry assessment and laboratory evaluation will be performed at baseline (T0), at week 4 (T1) and week 8 (T2). C-reactive protein (CRP) and immunoglobulin A (IgA) serum levels assessment will be performed at each visit. The proportion of CD4+ and CD8+ T cells, and Tregs (CD4+CD25+Foxp3+CD127low), and Th1, Th2 e Th17 CD4+ T cell subsets levels will be evaluated using flow cytometer at each visit in SSc patients and also in 50 healthy subjetcs.

Study Timeline

• Status Verified: 2014-11
• Study First Submitted: 2014-11-17
• Study First Submitted QC: 2014-11-24
• Last Update Submitted: 2014-11-24
• Study First Posted: 2014-11-27
• Last Update Posted: 2014-11-27
• Study Start: 2014-12
• Primary Completion: 2015-04
• Study Completion: 2016-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 76

Inclusion Criteria

• Patients with systemic sclerosis according to the 2013 ACR/EULAR classification criteria for SSc;
• Patients with gastrointestinal symptoms related to SSc including: gastrointestinal reflux, bloating, diarrhea and constipation;
• Written informed consent provided by the subjects.

Exclusion Criteria

• Overlap syndromes with systemic lupus erythematosus, polymyositis/dermatomyositis and rheumatoid arthritis;
• Use of antibiotics and/or probiotics four weeks before baseline;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Changes in the gastrointestinal symptoms as measured by the "The University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (GIT 2.0)" Questionnaire	baseline and eight weeks

Secondary Outcome Measures

Name	Time	Method
Scleroderma Health Assessment Questionnaire (sHAQ)	baseline and eight weeks
Food intake record	baseline and eight weeks
Anthropometry assessment as measured by the body mass index (BMI)	baseline and eight weeks
Th1, Th2 and Th17 CD4+ T cell subsets levels	baseline and eight weeks
Proportion of CD4+ and CD8+ T cells	baseline and eight weeks
Tregs (CD4+CD25+Foxp3+CD127low) levels	baseline and eight weeks
C-reactive protein (CRP) and immunoglobulin A (IgA) serum levels	baseline and eight weeks

Trial Locations

Locations (1)

Systemic Sclerosis Outpatient Clinic, Hospital São Paulo; 🇧🇷 São Paulo, SP, Brazil