Genetic Determinism of Epithelial Barrier Defects Induced by Increase in Proteases Activity in Irritable Bowel Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Clinical criteria
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with irritable bowel syndrome (IBS), defined by Rome III criteria (patient group)
- •Patients coming for screening colonoscopy (control group)
排除标准
- •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
研究组 & 干预措施
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
干预措施: Analysis on colorectal biopsy (Genetic)
结局指标
主要结局
Clinical criteria
时间窗: at day one
Transit disorders : Rome III criteria questionnaire
Clinical criteria
时间窗: at the medical visit
Abdominal Pain : Francis scoring
次要结局
- Experimental criteria(at day one)