Effect of Probiotic on Insulin Resistance in Type 2 Diabetes Patients

• ClinicalTrials.gov Identifier: NCT03434860
• Recruitment Status: Completed
• First Posted: February 15, 2018
• Last Update Posted: December 17, 2019
• Sponsor: Bogomolets National Medical University
• Information provided by (Responsible Party): Nazarii Kobyliak, Bogomolets National Medical University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Type2 Diabetes; Insulin Resistance; Probiotic	Dietary Supplement: probiotic; Dietary Supplement: placebo	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 53 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: 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
• Primary Purpose: Treatment
• Official Title: Effect of Alive Multistrain Probiotic on Insulin Resistance in Type 2 Diabetes Patients
• Actual Study Start Date: January 15, 2016
• Actual Primary Completion Date: November 20, 2016
• Actual Study Completion Date: January 25, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. HOMA-IR [ Time Frame: 8 weeks compared to baseline ]
   HOMA-IR was calculated according to the formula: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Sponsors and Collaborators

Bogomolets National Medical University

Investigators

• Principal Investigator: Petro Bodnar, Prof; Bogomolets National Medical University

More Information

Publications of Results:

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.

• Responsible Party: Nazarii Kobyliak, Associate Professor of Endocrinology Department, PhD, Bogomolets National Medical University
• ClinicalTrials.gov Identifier: NCT03434860
• Other Study ID Numbers: ENDO-4
• First Posted: February 15, 2018
• Last Update Posted: December 17, 2019
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism