Irritable Bowel Syndrome (IBS)PROTIBSNCT02841878
Genetic Determinism of Epithelial Barrier Defects in Irritable Bowel Syndrome
A study testing Analysis on colorectal biopsy in people with Irritable Bowel Syndrome (IBS), run by Centre Hospitalier Universitaire de Nice at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Irritable Bowel Syndrome (IBS)
- What is being tested?
- Analysis on colorectal biopsy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2016to Sep 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Genetic Determinism of Epithelial Barrier Defects Induced by Increase in Proteases Activity in Irritable Bowel Syndrome
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.
Read the 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.
- Conditions
- Irritable Bowel Syndrome (IBS)
- Being tested
- Analysis on colorectal biopsy
- Medical subject headings
- Irritable Bowel Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Analysis on colorectal biopsyGenetic
| Study group | Role | What they receive |
|---|---|---|
| analysis on colorectal biopsy | Other | * 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 Receives: Genetic: Analysis on colorectal biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical criteria
Abdominal Pain : Francis scoring
Measured: at the medical visit
Clinical criteria
Transit disorders : Rome III criteria questionnaire
Measured: at day one
Clinical criteria
Quality of life alteration (questionnaires)
Measured: at day one
Secondary outcomes (3)
Experimental criteria
Proteases activity (cystein and serin proteases)
Tight junctions genes expression Cytokines genes expression (TNFalpha, interleukines) Cellularity on histologic sections
Measured: at day one
Experimental criteria
Proteases inhibitors genes expression (Serpins A1 / E1)
Measured: at day one
Experimental criteria
Colonic biopsies permeability
Measured: at day one
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2016 (estimated)
- Study startSep 2016 (estimated)
- Primary completionSep 2018 (estimated)
- Study completionSep 2018 (estimated)
Why it stopped: Decision of the investigator
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Irritable Bowel Syndrome (IBS)Studies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NiceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nice
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thierry PICHE, MD, Principal investigator, Nice University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02841878
- Sponsor's protocol ID
- 14-PP-20
- Acronym
- PROTIBS
- Status last verified
- Feb 2018
- First submitted
- 24 Aug 2015
- Last updated
- 22 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Determinism of Epithelial Barrier Defects Induced by Increase in Proteases Activity in Irritable Bowel Syndrome
- ClinicalTrials.gov ID
- NCT02841878
- Acronym / sponsor ID
- PROTIBS / 14-PP-20
- Conditions
- Irritable Bowel Syndrome (IBS)
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Decision of the investigator
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de NiceUniversity, hospital or other
- Study start
- Sep 2016 (estimated)
- Primary completion
- Sep 2018 (estimated)
- Study completion
- Sep 2018 (estimated)
- First posted
- 22 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| analysis on colorectal biopsy | Other | Genetic: 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patient with irritable bowel syndrome (IBS), defined by Rome III criteria (patient group)
- Patients coming for screening colonoscopy (control group)
- Active inflammatory bowel disease
- Infectious bowel disease or other cause that could explain digestive symptoms
- Patients coming for screening colonoscopy without inflammatory bowel disease or IBS
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Analysis on colorectal biopsy | Genetic | analysis on colorectal biopsy |
Primary outcome
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)
3 secondary outcomes
Experimental criteria
Time frame: at day one
Experimental criteria
Time frame: at day one
Experimental criteria
Time frame: at day one
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thierry PICHE, MD principal investigator
Nice University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Analysis on colorectal biopsy in people with Irritable Bowel Syndrome (IBS), run by Centre Hospitalier Universitaire de Nice at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 22 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical criteria (time frame: at the medical visit). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2018.