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Genetic Determinism of Epithelial Barrier Defects in Irritable Bowel Syndrome (PROTIBS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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Recruitment Status : Withdrawn (Decision of the investigator)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

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.

Condition or disease Intervention/treatment Phase
Irritable Bowel Syndrome (IBS) Genetic: Analysis on colorectal biopsy Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Biopsy

Arm Intervention/treatment
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
Genetic: Analysis on colorectal biopsy



Primary Outcome Measures :
  1. Clinical criteria [ Time Frame: at the medical visit ]
    Abdominal Pain : Francis scoring

  2. Clinical criteria [ Time Frame: at day one ]
    Transit disorders : Rome III criteria questionnaire

  3. Clinical criteria [ Time Frame: at day one ]
    Quality of life alteration (questionnaires)


Secondary Outcome Measures :
  1. 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


  2. Experimental criteria [ Time Frame: at day one ]
    Proteases inhibitors genes expression (Serpins A1 / E1)

  3. Experimental criteria [ Time Frame: at day one ]
    Colonic biopsies permeability



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

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


Locations
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France
Department of gastroenterology, Hopital Archet 2
Nice, France, 06002
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
Investigators
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Principal Investigator: Thierry PICHE, MD Nice University Hospital
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Responsible Party: Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier: NCT02841878    
Other Study ID Numbers: 14-PP-20
First Posted: July 22, 2016    Key Record Dates
Last Update Posted: February 22, 2018
Last Verified: February 2018
Additional relevant MeSH terms:
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Irritable Bowel Syndrome
Syndrome
Disease
Pathologic Processes
Colonic Diseases, Functional
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases