Clinical trial NCT03494036: Effect of Synbiotic on Immune Response, Gut Permeability and Microbiota in Patient With Connective Tissue Disease
Official title: Effect of Synbiotic Supplementation on Interleukin 17 (IL-17) Level, Regulatory T-cells, Gut Permeability and Microbiota in Patient With Connective Tissue Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Connective Tissue Diseases
Keywords: synbiotic
probiotic
lupus
connective tissue disease
Lead sponsor: Fakultas Kedokteran Universitas Indonesia
Sponsor class: OTHER
First posted: 2018-04-11
Enrollment: 46
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a double blind randomized placebo controlled trial to determine the effect of synbiotic to FOXP3 regulatory T cells, IL-17, gut permeability and gut microbiota in patients with connective tissue disease. Synbiotic can increase FOXP3 regulatory T cells, decrease IL-17 and improve gut permeability and gut microbiota in patients with connective tissue disease.

Detailed description: Study showed gut microbiota has a role in the pathogenesis of autoimmune diseases. Gut microbiota which can increase gut permeability affect the antigen presentation to the immune system. Synbiotic supplementation is expected to improve immune system, gut permeability, and gut microbiota in patients with connective tissue disease.

The subjects who fulfill inclusion criteria, willing to participate and sign informed consent will be randomized into two groups: the group receiving synbiotic containing probiotic (Lactobacillus helveticus R0052 60%, Bifidobacterium infantis R0033 20%, dan Bifidobacterium bifidum R0071 20%) and 80 mg fructooligosaccharide (group I, n=23) and the group receiving placebo (group II, n=23). Both groups receive intervention for two months. Patients continue to receive their immunosuppressive drugs (corticosteroids, hydroxychloroquine, mycophenolate mofetil, azathioprine, or cyclosporine).

Percentage of FOXP3 Regulatory T-cells, serum IL-17, zonulin, high sensitivity C-reactive protein, and gut microbiota are evaluated at the beginning and at the end of the study. FOXP3 regulatory T-cell is evaluated by flowcytometry. Serum IL-17 and zonulin are measured by ELISA. Gut microbiota is evaluated using 16s ribosomal RNA gene next generation sequencing. The DNA from the stool is isolated by DNA stool mini kit (QIAamp).

The results are presented in mean ± standard deviation, median (IQR 25-75%) and n (%). The Kolmogorov-Smirnov test is used to determine the normality of the data, assuming the normality of the data is fulfilled if p\> 0.05. Bivariate analysis uses paired T test if the data has normal distribution. If the distribution is not normal, Wilcoxon test will be used. Differences are said to be significant when the value of p \<0.05.

Eligibility criteria: Inclusion Criteria:

* patients diagnosed with connective tissue disease
* has gastrointestinal symptoms (abdominal pain, diarrhea, constipation, or bloating)
* age between 18-60 years old

Exclusion Criteria:

* pregnant or breastfeeding
* acute infection
* on antibiotic treatment
* taking yoghurt or probiotic supplementation in the last 3 weeks before recruitment
* taking corticosteroid more than 20 mg prednison a day or equal\\
* refuse to join the study

Primary outcomes:
measure: FOXP3 regulatory T cell
timeFrame: 2 months
Secondary outcomes:
measure: IL-17
timeFrame: 2 months
measure: zonulin
timeFrame: 2 months
measure: gut microbiota
timeFrame: 2 months
Other outcomes:
Locations:
city: Jakarta
country: Indonesia
facility: Cipto Mangunkusumo Hospital
Study officials:
affiliation: Faculty of Medicine University of Indonesia
name: alvina widhani, MD
role: PRINCIPAL_INVESTIGATOR
References: