Smectite Gel and Probiotic for Obesity and Insulin Resistance

Study Overview
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Brief Summary
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Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Smectite is a natural silicate clay belonging to the dioctahedral smectite class formed from aluminomagnesium silicate. It is not absorbed from the gastrointestinal tract, but binds to intestinal mucous, forms multilayer structure with high plastic viscosity and powerful coating properties hence preserving integrity of the mucus, and has the ability to absorb directly bacterial toxins, bacteria, viruses and bile salts. The current study aim was to conduct placebo-controlled randomize clinical trial for the efficiency of a combination of multiprobiotics with smectite (Symbiter-Forte formulation) as an adjunction to the standard anti-diabetic therapy on IR, glycemic control parameters, β-cells functional activity, anthropometric parameters and markers of a chronic systemic inflammatory response in type 2 diabetes patients.

Detailed Description
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In this single-center double-blind, placebo controlled, parallel group study, 55 type 2 diabetes patients from the Kyiv City Clinical Endocrinology Center were selected. They were randomly assigned to receive Symbiter Smectite 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 Smectite was supplied by Scientific and Production Company O.D. Prolisok. It contains a biomass of alive probiotic microorganism symbiosis, colony forming units - CFU/g: Lactobacillus - 1.0х109, Bifidobacterium - 1.0х109, Lactococcus - 1.0х108, Propionibacterium - 1.0х108 and Acetobacter - 1.0х105; and smectite gel (250 mg). Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) of probiotic-smectite 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.

Official Title
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Co-administration of Smectite Gel With Live Probiotic Strains on Obesity Parameters and Insulin Resistance

Conditions
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Obesity, Insulin Resistance, Insulin Sensitivity, Type2 Diabetes Mellitus, Visceral Obesity

Intervention / Treatment
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* Dietary Supplement: Symbiter-Smectite
* 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) presence of type 2 diabetes 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); type 2 diabetes 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Symbiter-Smectite<br>Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) per day | Dietary Supplement: Symbiter-Smectite<br>* Symbiter-Smectite contains biomass of alive probiotic microorganism symbiosis, colony forming units - CFU/g: Lactobacillus - 1.0х109, Bifidobacterium - 1.0х109, Lactococcus - 1.0х108, Propionibacterium - 1.0х108 and Acetobacter - 1.0х105; and smectite gel (250 mg)<br>|
| Placebo Comparator: Placebo<br>Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) per day | Dietary Supplement: Placebo<br>* Placebo<br>|

What is the study measuring?
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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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smectite, Probiotic, Lactobacillus, Bifidobacterium, Propionibacterium, Acetobacter, Obesity, Type2 Diabetes, Insulin Resistance