Clinical trial NCT04293731: Smectite Gel and Probiotic for Obesity and Insulin Resistance
Official title: Co-administration of Smectite Gel With Live Probiotic Strains on Obesity Parameters and Insulin Resistance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Insulin Resistance
Insulin Sensitivity
Type2 Diabetes Mellitus
Visceral Obesity
Keywords: Smectite
Probiotic
Lactobacillus
Bifidobacterium
Propionibacterium
Acetobacter
Obesity
Type2 Diabetes
Insulin Resistance
Lead sponsor: Bogomolets National Medical University
Sponsor class: OTHER
Collaborators: name: Taras Shevchenko National University of Kyiv
First posted: 2020-03-03
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: HOMA-2IR
timeFrame: 8 weeks compared to baseline
measure: insulin sensitivity (%S)
timeFrame: 8 weeks compared to baseline
Secondary outcomes:
measure: HbA1c
timeFrame: 8 weeks compared to baseline
measure: fasting plasma glucose (FPG)
timeFrame: 8 weeks compared to baseline
measure: β-cell function (%B)
timeFrame: 8 weeks compared to baseline
measure: C-peptide
timeFrame: 8 weeks compared to baseline
measure: weight
timeFrame: 8 weeks compared to baseline
measure: waist circumferences (WC)
timeFrame: 8 weeks compared to baseline
measure: body mass index (BMI)
timeFrame: 8 weeks compared to baseline
measure: cytokines levels
timeFrame: 8 weeks compared to baseline
Other outcomes:
Locations:
city: Kyiv
country: Ukraine
facility: Bogomolets National Medical University
Study officials:
affiliation: Bogomolets National Medical University
name: Nazarii Kobyliak, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kobyliak N, Abenavoli L, Falalyeyeva T, Kovalchuk O, Kyriienko D, Komisarenko I. Metabolic Benefits of Probiotic Combination with Absorbent Smectite in type 2 Diabetes Patients a Randomised Controlled Trial. Rev Recent Clin Trials. 2021;16(1):109-119. doi: 10.2174/1574887115666200709141131.