Association Between High Faecal Calprotectin, Increased Intestinal Permeability and Visceral Hypersensitivity in IBS-D Patients

Not Applicable

Completed

• Conditions: Irritable Bowel Syndrome
• Interventions: Procedure: Colonoscopy with eleven biopsies in the left colon to assess intestinal permeability

• Registration Number: NCT02550704
• Lead Sponsor: University Hospital, Rouen

Brief Summary

Visceral hypersensitivity, low grade inflammation and increased intestinal permeability are three main pathophysiological mechanisms involved in irritable bowel syndrome. The connexion between these abnormalities is not known. We hypothesis there is a link between them in IBS with diarrhoea.

Detailed Description

Irritable bowel syndrome (IBS) is a common functional disorder which affect around 10% of the general population. Abdominal pain and discomfort are associated with transit disorders (diarrhea, constipation, alternating). IBS is defined by Rome III criteria.

For clinicians, IBS remains difficult to treat while its pathophysiology remains not completely understood. Visceral hypersensitivity, low grade inflammation and increased intestinal permeability are three abnormalities found in IBS patients. Visceral hypersensitivity is present in 60% of the patients, while intestinal permeability is increased in a subgroup of IBS with diarrhea. Low grade inflammation could be identify with faecal calprotectin dosage. The link between this three abnormalities is not clear.

The goal of our study is to describe the prevalence of these three abnormalities in IBS-Diarrhea population and to look for a correlation between low grade inflammation, visceral hypersensitivity, increased intestinal permeability and clinical phenotypes.

Study Timeline

• Study First Submitted: 2015-09-14
• Study First Submitted QC: 2015-09-14
• Study First Posted: 2015-09-15
• Study Start: 2016-05-20
• Primary Completion: 2021-05-20
• Study Completion: 2021-05-20
• Status Verified: 2021-09
• Last Update Submitted: 2022-05-19
• Last Update Posted: 2022-05-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

• IBS-Diarrhoea according to Rome III criteria,
• Faecal calprotectin ≤200 µg/g in the last two months
• 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
• Treatment such as anti-inflammatory, probiotic in the last three months
• Patient with blood dyscrasia disorder known or identified , anticoagulant or antiplatelet treatments
• Small intestinal bacterial overgrowth (identified by a glucose breath test)
• Hypersensitivity to Normacol
• Severe renal failure
• 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
• Diet based in grapes

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Irritable Bowel Syndrome with diarrhea	Colonoscopy with eleven biopsies in the left colon to assess intestinal permeability	Colonoscopy with eleven biopsies in the left colon to assess intestinal permeability. Intestinal permeability is not routinely performed and is assessed in colonic biopsies (occludin, claudin and ZO-1 by western blot, qPCR and immunofluorescence)

Primary Outcome Measures

Name	Time	Method
Occludin level expression in left colonic biopsies	day 1	Occludin expression is measured using western blot (for proteins), Quantitative Real Time Polymerase Chain Reaction (q RT-PCR) (RNA) and IF (for localization)
Faecal calprotectin level	day 1	Level is assessed on stool sample by ELISA kit in µg/g

Secondary Outcome Measures

Name	Time	Method
Zonula Occludens (ZO)-1 level expression	day 1	ZO-1 expression is measured using western blot (for proteins), q RT-PCR (for RNA) and IF (for localization)
Claudin level expression in left colonic biopsies	day 1	Claudin expression is measured using western blot (for proteins), q RT-PCR (for RNA) and IF (for localization)
Pression pain threshold by rectal barostat	day 1	Pression pain threshold is measured in mmHg during rectal barostat.
Quality of life by GIQLI	day 1	Evaluation of quality of life using the validated score : french version of the Gastrointestinal Quality of Life Index (GIQLI)
Abdominal symptoms	day 1	Abdominal symptoms of IBS are assessed with IBS symptom severity scale.
Anxiety and depression level	day 1	Anxiety and depression are assessed with the Hospital anxiety and depression scale.

Trial Locations

Locations (1)

Rouen University Hospital; 🇫🇷 Rouen, France