Probiotic Supplementation and Pancreatic β-Cell Function in Type 2 Diabetes

Efficacy and Safety of Multi-strain Probiotic on Pancreatic β-cell Function in Type 2 Diabetes Patients

Probiotics have beneficial effect on obesity related disorders in animal models. Current understanding for the beneficial effects of probiotics in type 2 diabetes strictly relies on animal and clinical data, which mainly focus on their impact on insulin resistance, anthropometric parameters, glycemic control and markers of chronic systemic inflammation. From the other hand, there is a lack of evidence-based probiotic efficacy on pancreatic β-cell function in terms of type 2 diabetes and related metabolic disorders. In this double-blind single center randomized clinical trial, effect of alive multistrain probiotic vs. placebo on pancreatic β-cell function in type 2 diabetes patient will be assessed.

Study Overview

• Status: Completed
• Conditions: Obesity; Insulin Resistance; Type2 Diabetes; Obesity, Abdominal
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Probiotic

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): 68
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Ukraine
  • Kyiv, Ukraine, 01601
    • Bogomolets National Medical University
  • Kyiv, Ukraine, 01601
    • Taras Shevchenko National University of Kyiv
  • Kyiv, Ukraine, 01601
    • Kyiv City Clinical Endocrinology Center
  • Lviv, Ukraine
    • Danylo Halytsky Lviv National Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult participants (aged 18 to 75);
• presence of T2D diagnosis based on the criteria of the American Diabetes Association (plasma glucose in fasting state ≥7.0 mmol/l; plasma glucose at random measuring ≥11.1 mmol/l; HbA1c ≥6.5% or glucose > 11.1 mmol/l 2 hours after tolerance test with 75 g of glucose);
• presence of pancreatic β-cell dysfunction which defined as HOMA2-β<50%;
• treatment with insulin therapy alone or in combination with oral anti-diabetic drugs (metformin and/or sulphonylureas) in a stable dose for at least 3 months prior to randomization;
• HbA1c level 6.5 to 11.0%;
• signed informed consent

Exclusion Criteria:

• presence of T1D;
• intake of anti-diabetic drugs except for those specified in the inclusion criteria (pioglitazone, glucagon-like peptide (GLP-1) analogs, dipeptide-peptidase 4 (DPP-4) inhibitors, etc.);
• severe diabetes-related complications at screening (ie, end-stage diabetic kidney disease, neuropathy requiring pharmacological treatment, proliferative retinopathy, autonomic neuropathy);
• regular intake of probiotics, prebiotics or antibiotics for 3 months prior the inclusion;
• previously diagnosed allergy to probiotics;
• gastrointestinal disorders including food allergy, gluten-sensitive enteropathy, ulcerative colitis;
• an uncontrolled cardiovascular or respiratory disease, an active malignant tumor or chronic infections;
• participant who had severe course of COVID-19 (extracorporeal membrane oxygenation, mechanically ventilated), and/or had a confirmed case of COVID-19 within 4 weeks prior to enrollment;
• participation in another clinical trial;
• pregnancy or lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: probiotic; The multiprobiotic 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.	Dietary supplement: Probiotic; The multiprobiotic 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 pa; Other Names: Symbiter
Placebo Comparator: placebo; Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) of gel 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
C-peptide	C-peptide, ng/ml	8 weeks compared to baseline
β-cell function (%B)	This model can be calculated using the software supplied by the Oxford Centre for Diabetes Endocrinology and Metabolism available at http://www.dtu.ox.ac.uk/homacalculator/index.php	8 weeks compared to baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HOMA-2IR	This model can be calculated using the software supplied by the Oxford Centre for Diabetes Endocrinology and Metabolism available at http://www.dtu.ox.ac.uk/homacalculator/index.php	8 weeks compared to baseline
insulin sensitivity (%S)	This model can be calculated using the software supplied by the Oxford Centre for Diabetes Endocrinology and Metabolism available at http://www.dtu.ox.ac.uk/homacalculator/index.php	8 weeks compared to baseline
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
body mass index (BMI)	weight in kg and height in meters will be combined to report BMI in kg/m^2	8 weeks compared to baseline
cytokines levels	TNF-α, IL-1β, IL-6, IL-8, INF-γ	8 weeks compared to baseline

Collaborators and Investigators

• Sponsor: Bogomolets National Medical University
• Collaborators: Danylo Halytsky Lviv National Medical University; Taras Shevchenko National University of Kyiv; Kyiv City Clinical Endocrinology Center
• Investigators: Principal Investigator: Nazarii Kobyliak, Bogomolets National Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): November 30, 2021
• Study Completion (Actual): December 15, 2021

Study Registration Dates

• First Submitted: March 1, 2023
• First Submitted That Met QC Criteria: March 10, 2023
• First Posted (Actual): March 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 13, 2023
• Last Update Submitted That Met QC Criteria: March 10, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: probiotics; type 2 diabetes; pancreatic β-cells
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hyperinsulinism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Obesity; Insulin Resistance; Obesity, Abdominal
• Other Study ID Numbers: ENDO-8

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