Clinical trial NCT02302352: Effects of Probiotics on Gastrointestinal Symptoms and on the Immune System in Patients With Systemic Sclerosis
Official title: Effects of Probiotics on Gastrointestinal Symptoms and on the Immune System in Patients With Systemic Sclerosis: a Randomized Double-blind Placebo-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Systemic Sclerosis
Scleroderma
Keywords: Probiotics
Immune system
Lead sponsor: Federal University of São Paulo
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2014-11-27
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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;

Primary outcomes:
measure: 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
timeFrame: baseline and eight weeks
Secondary outcomes:
measure: Scleroderma Health Assessment Questionnaire (sHAQ)
timeFrame: baseline and eight weeks
measure: Food intake record
timeFrame: baseline and eight weeks
measure: Anthropometry assessment as measured by the body mass index (BMI)
timeFrame: baseline and eight weeks
measure: C-reactive protein (CRP) and immunoglobulin A (IgA) serum levels
timeFrame: baseline and eight weeks
measure: Proportion of CD4+ and CD8+ T cells
timeFrame: baseline and eight weeks
measure: Tregs (CD4+CD25+Foxp3+CD127low) levels
timeFrame: baseline and eight weeks
measure: Th1, Th2 and Th17 CD4+ T cell subsets levels
timeFrame: baseline and eight weeks
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Systemic Sclerosis Outpatient Clinic, Hospital São Paulo
state: SP
Study officials:
affiliation: Associate Professor
name: Cristiane Kayser
role: PRINCIPAL_INVESTIGATOR
References:
citation: Marighela TF, Arismendi MI, Marvulle V, Brunialti MKC, Salomao R, Kayser C. Effect of probiotics on gastrointestinal symptoms and immune parameters in systemic sclerosis: a randomized placebo-controlled trial. Rheumatology (Oxford). 2019 Nov 1;58(11):1985-1990. doi: 10.1093/rheumatology/kez160.