Effect of Synbiotic on Immune Response, Gut Permeability and Microbiota in Patient With Connective Tissue Disease

Effect of Synbiotic Supplementation on Interleukin 17 (IL-17) Level, Regulatory T-cells, Gut Permeability and Microbiota in Patient With Connective Tissue Disease

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.

Study Overview

• Status: Completed
• Conditions: Connective Tissue Diseases
• Intervention / Treatment: Dietary supplement: Synbiotic; Dietary supplement: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Indonesia
  • Jakarta, Indonesia
    • Cipto Mangunkusumo Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Synbiotic; Synbiotic capsule containing 3x1.000.000.000 Colony Forming Units probiotics (Lactobacillus helveticus R0052 60%, Bifidobacterium infantis R0033 20%, dan Bifidobacterium bifidum R0071 20%) and fructooligosaccharide 80 mg. The dosage is once daily and it is given for 60 days	Dietary supplement: Synbiotic; capsule
PLACEBO_COMPARATOR: Placebo; Placebo capsule containing saccharum lactis. The dosage is once daily and it is given for 60 days	Dietary supplement: Placebo; capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FOXP3 regulatory T cell	change in the percentage of FOXP3 regulatory T cell	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IL-17	change in the serum IL-17 level	2 months
zonulin	change in the serum zonulin level	2 months
gut microbiota	change of the profile of gut microbiota	2 months

Collaborators and Investigators

• Sponsor: Fakultas Kedokteran Universitas Indonesia
• Investigators: Principal Investigator: alvina widhani, MD, Faculty of Medicine University of Indonesia

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2017
• Primary Completion (ACTUAL): July 31, 2018
• Study Completion (ACTUAL): August 31, 2018

Study Registration Dates

• First Submitted: March 31, 2018
• First Submitted That Met QC Criteria: March 31, 2018
• First Posted (ACTUAL): April 11, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 12, 2019
• Last Update Submitted That Met QC Criteria: March 10, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: probiotic; synbiotic; lupus; connective tissue disease
• Additional Relevant MeSH Terms: Connective Tissue Diseases
• Other Study ID Numbers: 804/UN2.F1/ETIK/2017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No