Effect of Probiotic Co-administration With Omega-3 Fatty Acids on Obesity Parameters and Insulin Resistance (ENDO-5)

Probiotic With Omega-3 Fatty Acids on Obesity and Insulin Resistance Management in Patients With Type 2 Diabetes

Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Omega-3 fatty acids belong to the family of polyunsaturated fatty acids. They are known to exert a strong positive influence on metabolism and inflammation. The data from animal studies suggested that both probiotics and omega-3 can affect body weight, influence on glucose and fat metabolism, improve insulin sensitivity and reduce chronic systemic inflammation. In respect to experimental data, the current study aim was to provide double-blind single center RCT, for study the efficacy of co-administration of probiotic with omega-3 vs. placebo in type 2 diabetes patient

Study Overview

• Status: Completed
• Conditions: Obesity; Insulin Resistance; Type2 Diabetes; Insulin Sensitivity; Visceral Obesity
• Intervention / Treatment: Dietary supplement: Placebo; Combination product: Symbiter-Omega

Detailed Description

In this single-center double-blind, placebo controlled, parallel group study, 56 type 2 diabetes patients from the Kyiv City Clinical Endocrinology Center were selected. They were randomly assigned to receive "Symbiter Omega" or placebo for 8 weeks, administered as a sachet formulation in double-blind treatment. Randomization was done by the study statistician based on a computer-generated list. The groups were homogeneous according to age, sex and diagnostic criteria. The assignment of groups was 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 "Symbiter Omega" was supplied by Scientific and Production Company "O.D. Prolisok". It contains combination of flax and wheat germ oil (250 mg of each, concentration of omega-3 fatty acids 1-5%), supplemented with biomass of 14 alive probiotic strains: 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-omega and placebo per day. All sachets were identical with similar organoleptic characteristics (e.g., taste and appearance).

The pre-randomization period was 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 were instructed in one-on-one sessions with a dietitian to follow a therapeutic lifestyle-change diet as classified by the NCEP. In addition, participants were instructed to continue with stable anti-hyperglycemic treatment and received standardized mild physical training for 1 hour per day.

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

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Ukraine
  • Kyiv, Ukraine, 01601
    • Bogomolets National Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• adult participants (ages 18-75, BMI ≥25 kg/m2)
• presence of T2D diagnosed according to criteria of the American Diabetes Association (fasting plasma glucose (FPG)≥7.0mmol/l, random plasma glucose ≥11.1mmol/l, HbA1c ≥6.5%, or glucose higher than 11.1mmol/l 2 hours after a 75-g oral glucose load);
• T2D duration 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-2IR≥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;
• allergy on probiotics or their components;
• presence of gastrointestinal diseases such as food allergy, celiac disease, non-specific ulcerative colitis;
• 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 Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Symbiter-Omega; Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) per day	Combination product: Symbiter-Omega; Symbiter-Omega contains combination of flax and wheat germ oil (250 mg of each, concentration of omega-3 fatty acids 1-5%), supplemented with biomass of 14 alive probiotic strains: Lactobacillus + Lactococcus (6×1010 CFU/g), Bifidobacterium (1×1010/g), Propionibacterium (3×1010/g), Acetobacter (1×106/g) genera.
Placebo Comparator: Placebo; Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) of gel per day	Dietary supplement: Placebo; Placebo

What is the study measuring?

Primary 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

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
β-cell function (%B)	(%B)	8 weeks compared to baseline
C-peptide	C-peptide, ng/ml	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
• Collaborators: Taras Shevchenko National University of Kyiv
• Investigators: Principal Investigator: Nazarii Kobyliak, PhD, Bogomolets National Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2018
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): January 15, 2019

Study Registration Dates

• First Submitted: December 15, 2019
• First Submitted That Met QC Criteria: December 15, 2019
• First Posted (Actual): December 17, 2019

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Obesity; Insulin Resistance; Probiotic; Lactobacillus; Bifidobacterium; Propionibacterium; Omega-3 Fatty Acids; Type2 Diabetes; Acetobacter
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hyperinsulinism; Diabetes Mellitus, Type 2; Obesity; Insulin Resistance; Obesity, Abdominal
• Other Study ID Numbers: ENDO-5

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