Effect of Probiotic on Insulin Resistance in Type 2 Diabetes Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Type2 Diabetes, Insulin Resistance, Probiotic

Intervention / Treatment
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* Dietary Supplement: probiotic
* Dietary Supplement: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: probiotic<br>Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) per day. | Dietary Supplement: probiotic<br>* 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.<br>|
| Placebo Comparator: placebo<br>Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) per day. | Dietary Supplement: placebo<br>* Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) of gel per day<br>|

What is the study measuring?
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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 insulins (FPI) | FPI in microU/L | 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 and height 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 |