Effects of Probiotic VSL#3 on Expression of Small Intestinal Renin-angiotensin System

Study Overview
=================
Brief Summary
-----------------
Probiotics have become very popular and are by WHO defined as Live microorganisms which when administered in adequate amounts confer a health benefit on the host. For example, probiotics have been shown to contribute to improvements of abdominal discomfort and intestinal inflammation. The main hypothesis behind the present study is that probiotics influences mucosal regulatory systems, particularly the actions of the hormone Angiotensin II locally in the intestinal mucosa.

Official Title
-----------------
Effects of Probiotic VSL#3 on Expression of Small Intestinal Mucosal Renin-angiotensin System and Glucose Absorption in Man - a Doubleblind, Randomized Parallel Arm Placebo Controlled Exploratory Study in Healthy Volunteers

Conditions
-----------------
the Local Renin-angiotensin System (RAS) in Small Intestinal Mucosa in Man

Intervention / Treatment
-----------------
* Biological: VSL#3
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: healthy volunteers of both sexes between 18 and 65 years of age. BMI between 18-25 kg/m2 Exclusion Criteria: Any drug abuse Use of prescription medication within the previous 14 days (with the exception of contraceptives) Pregnant or breast feeding woman or woman of childbearing potential not using adequate birth control (e.g. IUD, barrier method, oral contraceptive, abstinence) In the investigator's judgement, clinically significant abnormalities at the screening examination or in the laboratory test results.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

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

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

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

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: VSL#3<br> | Biological: VSL#3<br>* The probiotic product VSL#3® comes in a powder (sachet) that is to be dissolved in half a glass of cold water before ingestion. Two sachets are ingested once daily over 2 weeks. Each dose (sachet) contains 450 billion live (lyophilized) lactic acid bacteria (in defined ratios of the following strains: Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus bulgaricus, Streptococcus thermophilus) and are delivered in a base of maltose and silicon dioxide.<br>|
| Placebo Comparator: Inactive treatment<br> | Biological: Placebo<br>* Two placebo sachets containing maltose and silicon dioxide are given once daily over 2 weeks.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in mucosal expression of components of renin-angiotensin (particularly ACE1, AT1-receptor, AT2-receptor) | Mucosal biopsies from jejunum are sampled via endoscopy immediately before (baseline) and at the end of the 2 weeks treatment period. Protein expressions are assessed by western blotting and the subject acts as its own control. | Change from baseline in protein expressions after 2 weeks of treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in epithelial permeability and glucose absorption capacity in vitro | Mucosal biopsies are mounted in modified Ussing chambers. Permeability and glucose-absorption are assessed. | Change from baseline at 2 weeks after start of treatment. | 
| Change in intestinal glucose absorption capacity in-vivo | Glucose (75g) with an non-metabolisable analogue (3-O-methyl-glucose; 2g) is instilled into the duodenum via a nasogastroduodenal tube (corresponding to an oral glucose tolerance test). Plasma glucose, 3OMG and insulin are assessed in 15 min periods over 2h. | Change from baseline at 2 weeks after start of treatment. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
renin, angiotensin, probiotic, glucose absorption, intestinal