Is There Any Correlation Between Plasmatic Zonulin and Expression of Intestinal Tight Junction Proteins in IBS Patients?

Study Overview
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Brief Summary
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Increased intestinal permeability is one of the main pathophysiological mechanisms involved in irritable bowel syndrome. The expression of some intestinal tight junction proteins is decreased mostly in IBS-diarrhoea patients. This decrease is correlated with increased intestinal permeability. Currently, no test used in clinical practice could assess intestinal permeability. We hypothesis plasmatic zonulin could reflect intestinal permeability in IBS patients.

Detailed Description
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The goal of our study is to look for a correlation between plasmatic zonulin and increased colonic permeability (assessed by the expression of intestinal tight junction proteins by western blot) in IBS patients and to look for a role of intestinal low-grade inflammation and microbiota. Population : IBS patients with diarrhoea or IBS with constipation or mixed with worsening of symptoms Outcomes measures : Plasmatic zonulin (ELISA kit) Occludin expression in colonic biopsies (western blot)

Official Title
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Assessment of Intestinal Barrier in Irritable Bowel Syndrome Patients : Is There Any Correlation Between Plasmatic Zonulin and Expression of Intestinal Tight Junction Proteins ?

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Procedure: colonoscopy with biopsies in the left colon to assess intestinal permeability


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: IBS-Diarrhoea, IBS-constipation or alternating with recent worsening of symptoms, according to Rome III criteria Effective contraception since 1 month for women in childbearing age Exclusion Criteria: Patients with organic and/or inflammatory digestive disease IBS with constipation or alternating without clinical warning sign Treatment such as anti-inflammatory, probiotic in the last three months Severe renal failure Hypersensitivity to Normacol Patient with blood dyscrasia disorder known or identified, anticoagulant or antiplatelet treatments Anal pathology (anal fissure, hemorrhoidal thrombosis) Pregnant or breastfeeding women Person with administrative or judicial decision or under legal protection measure Patient participating in another trial in the last two weeks

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: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Irritable Bowel Syndrome<br> | Procedure: colonoscopy with biopsies in the left colon to assess intestinal permeability<br>* Eleven colonic biopsies are taken in the left colon during colonoscopy. Intestinal permeability is assessed by western blot, qPCR and immunofluorescence for claudin; occludin and ZO-1. One blood sample is taken to assess plasmatic zonulin (ELISA kit).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| occludin level expression in left colonic biopsies | occludin expression is measured using western blot (for proteins), q RT-PCT (for RNA) and IF (for localization). Plasmatic zonulin is measured in plasma using ELISA kit. | day 1 | 
| plasmatic zonulin expression | Plasmatic zonulin expression is done using ELISA kit | day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Claudin and ZO-1 level expression in left colonic biopsies | Claudin and ZO-1 expression is measured using western blot (for proteins), q RT-PCT (for RNA) and IF (for localization) | day 1 | 
| Faecal calprotectin level | Level is assessed on stool sample by ELISA kit in µg/g | day 1 | 
| Quality of life (GIQLI) | Evaluation of quality of life using the validated score : french version of the Gastrointestinal Quality of Life Index (GIQLI). | day 1 | 
| Abdominal symptoms | Abdominal symptoms of IBS are assessed with IBS symptom severity scale. | day 1 | 
| Anxiety and depression levels | Anxiety and depression are assessed with the Hospital anxiety and depression scale. | day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plasmatic zonulin, Irritable Bowel Syndrome, Intestinal permeability