Genetic Determinism of Epithelial Barrier Defects in Irritable Bowel Syndrome (PROTIBS)
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|ClinicalTrials.gov Identifier: NCT02841878|
Recruitment Status : Withdrawn (Decision of the investigator)
First Posted : July 22, 2016
Last Update Posted : February 22, 2018
|Condition or disease||Intervention/treatment||Phase|
|Irritable Bowel Syndrome (IBS)||Genetic: Analysis on colorectal biopsy||Not Applicable|
Irritable bowel syndrome (IBS) is the first reason for consultation in gastroenterology and his prevalence reach 5% of the general population. IBS is characterized by abdominal discomfort, diarrhea or constipation and decreased quality of life.
Recent facts on IBS pathophysiology show association between mucosal immunity activation (mast cells and their proteases) and epithelial permeability disorder. Permeability disorder can be reproduced by application of colonic biopsies cultures supernatants on in-vitro cell cultures. In parallel, tight junctions proteins mRNA (ZO-1, Occludin) decrease is observed ex-vivo in biopsies and in-vitro.
Gut bacterial proteases (cystein and serin proteases) may also play a role. In human, proteases activity is correlated with IBS symptoms severity. Proteases activity increase (cystein and serin proteases) is poorly understood, and this increase could be subjected to a genetic determinism (decrease in proteases inhibitors genes expression - Serpin A1/E1).
Objectives: 1/ To study relations between proteases activity (in stool and colonic biopsies supernatants), proteases inhibitors genes expression and mucosal cellular infiltrate (IBS patients and healthy subjects). 2/ Establishing a correlation between proteases activity, mucosal micro-inflammation and symptoms. 3/ To evaluate proteases inhibitors therapeutic potential.
Method: Subjects will be recruited in gastroenterology consultation. IBS patients will answer to Rome III criteria. Patients coming for screening colonoscopy will be defined as healthy subjects.
Colonic biopsies will be sent in real time to the research laboratory (EA 6302) for supernatants collecting, mRNA expression studies (Serpins, ZO-1, occludin, cytokines), proteases activity / permeability measurements and proteases inhibitors reversibility tests. Histologic study will also be performed.
Expected results: 1/ Decreased expression of proteases inhibitors genes in subjects with IBS. 2/ Correlation of symptoms with proteases activity intensity. 3/ Demonstration of restorative potential of proteases inhibitors.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Genetic Determinism of Epithelial Barrier Defects Induced by Increase in Proteases Activity in Irritable Bowel Syndrome|
|Estimated Study Start Date :||September 2016|
|Estimated Primary Completion Date :||September 2018|
|Estimated Study Completion Date :||September 2018|
analysis on colorectal biopsy
Genetic: Analysis on colorectal biopsy
- Clinical criteria [ Time Frame: at the medical visit ]Abdominal Pain : Francis scoring
- Clinical criteria [ Time Frame: at day one ]Transit disorders : Rome III criteria questionnaire
- Clinical criteria [ Time Frame: at day one ]Quality of life alteration (questionnaires)
- Experimental criteria [ Time Frame: at day one ]
Proteases activity (cystein and serin proteases)
Tight junctions genes expression Cytokines genes expression (TNFalpha, interleukines) Cellularity on histologic sections
- Experimental criteria [ Time Frame: at day one ]Proteases inhibitors genes expression (Serpins A1 / E1)
- Experimental criteria [ Time Frame: at day one ]Colonic biopsies permeability
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02841878
|Department of gastroenterology, Hopital Archet 2|
|Nice, France, 06002|
|Principal Investigator:||Thierry PICHE, MD||Nice University Hospital|