Effect of Probiotic Co-administration With Omega-3 Fatty Acids on Obesity Parameters 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. 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

Detailed Description
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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.

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

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

Intervention / Treatment
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* Combination Product: Symbiter-Omega
* 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 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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-Omega<br>Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) per day | Combination Product: Symbiter-Omega<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) of gel 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 insulins (FPI) | FPI in microU/L | 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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Omega-3 Fatty Acids, Probiotic, Lactobacillus, Bifidobacterium, Propionibacterium, Acetobacter, Obesity, Type2 Diabetes, Insulin Resistance