Probiotics and Endotoxemia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether probiotic treatment of overweight volunteers consuming high fat diet is able to reduce plasma lipopolysaccharide concentration.

Official Title
-----------------
Probiotics and Endotoxemia in Humans

Conditions
-----------------
Metabolic Endotoxemia, Metabolic Syndrome

Intervention / Treatment
-----------------
* Dietary Supplement: Probiotic bacterium Bifidobacterium lactis


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body mass index ≥ 27 kg/m2; above 18 years of age Used to eat high fat diet (more than 40% of total energy intake) Exclusion Criteria: Treated cardiovascular risk factors, treated hypertension, treated dyslipidemia, treated diabetes; Known diabetes, hypertension, dyslipidemia Severe illnesses Artificial heart valve Immunosuppression Regular consumption of probiotics History of bariatric surgery Consumption or wish to consume Orlistat Participation in other research Pregnancy or wishing/trying to get pregnant Inability to follow protocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic<br> | Dietary Supplement: Probiotic bacterium Bifidobacterium lactis<br>* Probiotic placebo controlled intervention<br>* Other names: Bifidobacterium animalis subsp. lactis;|
| Placebo Comparator: Placebo<br> | Dietary Supplement: Probiotic bacterium Bifidobacterium lactis<br>* Probiotic placebo controlled intervention<br>* Other names: Bifidobacterium animalis subsp. lactis;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of plasma endotoxin (plasma levels of lipopolysaccharides) in the volunteers before and after the 12 week intervention | Quantitative, kinetic assay for the detection of gram negative bacterial endotoxin (lipopolysaccharide) is used to test whether the probiotic intervention can reduce plasma endotoxin levels (IU/ml) compared to the baseline. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volunteer weight before and after the 12 week intervention. |  | 12 weeks | 
| Volunteer waist perimeter before and after the 12 week intervention |  | 12 weeks | 
| Insulin resistance (HOMA-IR index), glycemia, insulinemia and glycated hemoglobin in the volunteers before and after the 12 week intervention | Insulin resistance (IR) will be quantified in the non-diabetic adults using the HOMA-IR index calculated as the product of fasting plasma insulin (in microunits per milliliter) and fasting plasma glucose (in millimoles per liter), divided by 22.5. Higher HOMA values indicate higher IR. Glycated haemoglobin is used as a biological measure indicator of blood glucose concentration over 3 months. | 12 weeks | 
| Brachial blood pressure of the volunteers before and after the 12 week intervention. |  | 12 weeks | 
| Blood lipids in the volunteers before and after the 12 week intervention. | Plasma total cholesterol and triglycerides are measured by enzymatic methods. High-density lipoprotein (HDL) cholesterol is measured in the supernatant after sodium phosphotungstate/magnesium chloride precipitation. Low-density lipoprotein (LDL) cholesterol is determined by the Friedewald formula. | 12 weeks | 
| Serum inflammatory markers of volunteers before and after the 12 week intervention. | IL-6 (Interleukin-6) level is measured by an immunoenzymatic method, sCD14 is measured using an immuno-enzymatic method, and C reactive protein (CRP) levels is measured by an immunonephelemetric method. | 12 weeks | 
| Intestinal microbiota composition measured from stool samples before and after the 12 week intervention. | Stool samples are collected before and after the intervention and stored frozen until analysis. Bacterial DNA is extracted from the samples and relevant bacterial groups including genus Bifidobacterium, species Bifidobacterium animalis subsp. lactis, Enterobacteriaceae, Escherichia coli, Bacteroidetes and Lactobacillus are measures with quantitative real-time PCR. | 12 weeks | 
| Gut function questionaire as a measure of tolerability | Questionaire is used to assess the tolerability of the probiotic supplementation. Questionaire includes questions on frequency and severity of flatulence and bloating, occurence of diarhea, frequency of defecation, and texture of feces using a stool chart. | Symptoms during last 6 days |