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

Federal University of São Paulo

Status and phase

Unknown

Phase 3

Conditions

Scleroderma

Systemic Sclerosis

Treatments

Other: Placebo

Other: Probiotic

Study type

Interventional

Funder types

Other

Identifiers

NCT02302352

2013/26788-3

Details and patient eligibility

About

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.

Full 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.

Enrollment

76 estimated patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

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;

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

76 participants in 2 patient groups, including a placebo group

Probiotic

Active Comparator group

Description:

Oral probiotic 1g, once/day, containing: Lactobacillus paracasei, 10x9 CFU; Lactobacillus rhamnosus,10x9 CFU; Lactobacillus acidophillus, 10x9 CFU; Bifidobacterium lactis 10x9 CFU per sachet

Treatment:

Other: Probiotic

Placebo

Placebo Comparator group

Description:

Maltodextrin 1g per sachet, once/day

Treatment:

Other: Placebo