Effect of Probiotic on Insulin Resistance in Type 2 Diabetes Patients

Effect of Alive Multistrain Probiotic on Insulin Resistance in Type 2 Diabetes Patients

Probiotics have beneficial effect on obesity related disorders in animal models. Despite a large number of animal data, randomized placebo-controlled trials (RCT) concluded that probiotics have a moderate effect on glycemic control-related parameters. However, effect of probiotics on insulin resistance are inconsistent. In this double-blind single center RCT, effect of alive multistrain probiotic vs. placebo on insulin resistance in type 2 diabetes patient will be assessed.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance; Type2 Diabetes; Probiotic
• Intervention / Treatment: Dietary supplement: probiotic; Dietary supplement: placebo

Detailed Description

In this single-center double blind, placebo controlled, parallel group study, type 2 diabetes patients from the Kyiv City Clinical Endocrinology Center will be selected. They will be randomly assigned to receive multiprobiotic "Symbiter" or placebo for 8-weeks administered as a sachet formulation in double-blind treatment. Randomization will be done by the study statistician based on a computer-generated list. The groups will be homogeneous according to age, sex and diagnostic criteria. The assignment of groups will be blind to participants, research staff and outcome assessors moreover, to maintain blind parallel study the statistician was not aware of the allocation of participants to intervention.

The multiprobiotic "Symbiter" will be supplied by Scientific and Production Company "O.D. Prolisok". It contains of 14 alive probiotic strains of Lactobacillus + Lactococcus (6×1010 CFU/g), Bifidobacterium (1×1010/g), Propionibacterium (3×1010/g), Acetobacter (1×106/g) genera. Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) of probiotic and placebo per day. All sachets were identical with similar organoleptic characteristics (e.g., taste and appearance).

The pre-randomization period designed to minimize the effects of dietary changes on metabolic markers. For this purpose, 2 weeks before the study start, after inform consent signed, patients will be instructed in one-on-one sessions with a dietitian to follow a therapeutic lifestyle-change diet as classified by the NCEP. In addition, participants will be instructed to continue with stable anti-hyperglycemic treatment and received standardized mild physical training for 1 hour per day.

Patients who underwent study will be instructed to take the trial medication as prescribed. Throughout the study, weekly phone follow-up visits will be provided for assessment of compliance, adherence to the protocol, as well as the recording of adverse events. The effectiveness of therapy will be compared and evaluated separately in the two groups.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult participants (ages 18-75, BMI ≥25 kg/m2) diagnosed with T2D according WHO (1999) for at least 6 months prior to the study;
• patient who treated with diet and exercise alone or metformin, SUs and insulin on a stabilized dose for at least 3 months before the study;
• presence of insulin resistance established as HOMA-IR≥2.0;
• HbA1c between 6.5 and 11.0 %;
• written informed consent.

Exclusion Criteria:

• presence of type 1 diabetes;
• treatment with other than mention in inclusion criteria antidiabetic drugs (pioglitazone, GLP-1 analogues, DPP IV inhibitors etc);
• regular use of a probiotic or prebiotic supplement within 3 months prior to enrollment;
• antibiotic use within 3 months prior to enrollment;
• uncontrolled cardiovascular or respiratory disease, decompensated liver disease including ascites, encephalopathy or variceal bleeding, active malignancy, or chronic infections;
• participation in other clinical trials;
• presence of pregnancy or lactation.

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
ACTIVE_COMPARATOR: probiotic; Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) per day.	Dietary supplement: probiotic; The multiprobiotic "Symbiter" which contains of 14 alive probiotic strains of Lactobacillus + Lactococcus (6×1010 CFU/g), Bifidobacterium (1×1010/g), Propionibacterium (3×1010/g), Acetobacter (1×106/g) genera. Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) of probiotic per day.
PLACEBO_COMPARATOR: placebo; Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) per day.	Dietary supplement: placebo; Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) of gel per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HOMA-IR	HOMA-IR was calculated according to the formula: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5	8 weeks compared to baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c	HbA1c in %	8 weeks compared to baseline
fasting plasma glucose (FPG)	FPG in mmol/L	8 weeks compared to baseline
weight	weight in kg	8 weeks compared to baseline
waist circumferences (WC)	WC in cm	8 weeks compared to baseline
cytokines levels	TNF-α, IL-1β, IL-6, IL-8, INF-γ	8 weeks compared to baseline
fasting plasma insulins (FPI)	FPI in microU/L	8 weeks compared to baseline
body mass index (BMI)	weight and height will be combined to report BMI in kg/m^2	8 weeks compared to baseline

Collaborators and Investigators

• Sponsor: Bogomolets National Medical University

Publications and helpful links

General Publications

• Kobyliak N, Falalyeyeva T, Mykhalchyshyn G, Kyriienko D, Komissarenko I. Effect of alive probiotic on insulin resistance in type 2 diabetes patients: Randomized clinical trial. Diabetes Metab Syndr. 2018 Sep;12(5):617-624. doi: 10.1016/j.dsx.2018.04.015. Epub 2018 Apr 10.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 15, 2016
• Primary Completion (ACTUAL): November 20, 2016
• Study Completion (ACTUAL): January 25, 2017

Study Registration Dates

• First Submitted: January 21, 2018
• First Submitted That Met QC Criteria: February 14, 2018
• First Posted (ACTUAL): February 15, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 17, 2019
• Last Update Submitted That Met QC Criteria: December 15, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance
• Other Study ID Numbers: ENDO-4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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