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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Recruitment Status : Withdrawn (Decision of the investigator)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
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nice

Tracking Information
First Submitted Date  ICMJE August 24, 2015
First Posted Date  ICMJE July 22, 2016
Last Update Posted Date February 22, 2018
Estimated Study Start Date  ICMJE September 2016
Estimated Primary Completion Date September 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2016)
  • 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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2016)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Genetic Determinism of Epithelial Barrier Defects in Irritable Bowel Syndrome
Official Title  ICMJE Genetic Determinism of Epithelial Barrier Defects Induced by Increase in Proteases Activity in Irritable Bowel Syndrome
Brief Summary Irritable bowel syndrome (IBS) profoundly affects the quality of life. Mucosal micro-inflammation, epithelial permeability disorder and proteases activity increase have been demonstrated in the patients' gastrointestinal tract. Protease activity increase could be subjected to a genetic determinism (decrease in proteases inhibitors genes expression). 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. 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.
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Irritable Bowel Syndrome (IBS)
Intervention  ICMJE Genetic: Analysis on colorectal biopsy
Study Arms  ICMJE analysis on colorectal biopsy
  • Proteases activity (cystein and serin proteases)
  • Proteases inhibitors genes expression (Serpins A1 / E1)
  • Colonic biopsies permeabilityTight junctions genes expression
  • Cytokines genes expression (TNFalpha, interleukines)
  • Cellularity on histologic sections
Intervention: Genetic: Analysis on colorectal biopsy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: February 15, 2018)
0
Original Estimated Enrollment  ICMJE
 (submitted: July 19, 2016)
70
Estimated Study Completion Date  ICMJE September 2018
Estimated Primary Completion Date September 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patient with irritable bowel syndrome (IBS), defined by Rome III criteria (patient group)
  • Patients coming for screening colonoscopy (control group)

Patients exclusion criteria :

  • Active inflammatory bowel disease
  • Infectious bowel disease or other cause that could explain digestive symptoms

Healthy subjects inclusion criteria :

  • Patients coming for screening colonoscopy without inflammatory bowel disease or IBS
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02841878
Other Study ID Numbers  ICMJE 14-PP-20
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Centre Hospitalier Universitaire de Nice
Study Sponsor  ICMJE Centre Hospitalier Universitaire de Nice
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Thierry PICHE, MD Nice University Hospital
PRS Account Centre Hospitalier Universitaire de Nice
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP