Ileal Crohn's Disease and Post-operative Outcome: Prospective Cohort Study of the REMIND Group
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 575
- 试验地点
- 27
- 主要终点
- Study of Treatments efficacy to prevent recurrence
研究概览
简要总结
Crohn's disease (CD), a chronic inflammatory process in intestinal segments leads to tissue damage. More than two thirds of CD patients need intestinal resection. Symptomatic clinical recurrence occurs in 60% by 10 years. The principal factors affecting postoperative recurrence are active smoking, penetrating disease, perianal lesions history, prior intestinal resection, small bowel resection extent, and prophylaxis treatment absence.
Ileocolonoscopy within one year of surgery can predict clinical recurrence risk.
Different therapies are proposed after surgery, to prevent post-operative recurrence : Thiopurines, 6-mercaptopurine (positive for clinical and endoscopic postoperative recurrence prevention), Anti-tumour necrosis factor therapy (anti-TNF), the most effective therapy.
Intestinal microbiota acts as a central factor in the CD pathogenesis, and fecal stream role is clearly shown. Various changes in luminal flora with a possible link to local inflammation was also demonstrated. Bacteria associated with postoperative recurrence could be more pathogenic as adherent invasive E coli (AIEC), which could be a pathogen in CD through several mechanisms including increased mucosal colonization, adherence, replication and induction of TNF secretion. Alternatively, postoperative CD recurrence could be linked to a protective commensal species lack, such as Faecalibacterium prausnitzii.
Microscopic inflammation occurs as early as 8 days after anastomosis in the neoterminal ileum mucosa. IL6, IL10 and TGFb levels, measured in neoterminal ileum early after surgery are associated with different rates of postoperative recurrence. It suggests cytokines implication in postoperative recurrence. T cells are major players in the intestinal immune response. The presence at time of surgery and persistence of disease inducing T cell clonal expansions could play an important role in post-operative recurrence.
The main objective is to define a classification of ileal Crohn's Disease based on data integration on a large cohort of patients.
详细描述
Crohn's Disease is a major health issue with a complex etiology and despite available medical treatment, patients endure poor quality of life. The disease 's characterization on a molecular level will allow for a better management of patients treatment. To do so, the strategy is to integrate precise prospective clinical records with extensive biological data in a large cohort of patients.
All the clinical centers, participating to the study, include patients, with a tight collaboration between Gastroenterology and Surgery departments. Demographics and clinical parameters are collected in an eCRF.
Inclusion of patients is performed, before a scheduled ileocecal resection or ileal resection, and after eligibility criteria checking, and consent form signature. During surgery, several samples are collected : blood samples, mucosal biopsies, and surgical specimens. As usual practice, post-operative treatment will be prescribed at investigator's discretion, with help of a pre-established algorithm. Then, an endoscopic exam is scheduled, at least 6 months after surgery, or at least 6 months after intestine continuity restoration, in case of temporary stoma. Several samples are also collected during this exam (blood, ileal and colon biopsies).
At the same time as these 2 visits, clinical data regarding medical history, CD history, surgical history, treatments history, post-operative treatment if prescribed, treatments history between surgery and colonoscopy 6 months later, endoscopic score. Clinical data are also collected 18 months after surgery during a scheduled visit organized as usual practice, for long-term study : Clinical relapse, surgical recurrence, change in the therapy, hospitalizations and complications A patient has achieved the study after the endoscopic exam.
Several studies will be performed along the cohort setting-up:
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent obtained before any study-related activities
- •A diagnosis of CD, based on clinical, radiologic, endoscopic, or histological evidence.
- •Men and women ≥18 years of age
- •Required surgical intervention consisting in an ileocecal resection
排除标准
- •Previous history of dysplasia or cancer in the ileum or colon
- •Unwillingness or inability to follow the procedures outlined in the protocol
- •Pregnant women
研究组 & 干预措施
Crohn's disease patients
Patients aged 18 or more, for whom Crohn's disease diagnosis is confirmed and ileum or ileocecal Crohn's disease require surgical resection. in addition to usual practice, a bio-banking (blood samples, biopsies and surgical specimens) is collected.
干预措施: bio-banking collection (Other)
结局指标
主要结局
Study of Treatments efficacy to prevent recurrence
时间窗: 6 months after surgery time
During a clinical visit, scheduled as usual practice 6 months after surgery, clinical data will be collected : treatment modification or optimization, recurrence occurrence. If treament modification or optimization is needed (clinical symptoms or endoscopic recurrence), or complication occurs (abcess, occlusive syndrom, new surgery), patient will be considered as suffering a long-term relapse
Postoperative recurrence study
时间窗: 6 months after surgery
Rates of endoscopic recurrence as defined by a Rutgeerts score ≥ 1 in patients will be evaluated at the endoscopic exam
Identification of biomarkers which could predict postoperative recurrence and response to treatments
时间窗: surgery time, Time 0
Identification of biomarkers taking into account clinical data, immunological, genetic, microbiota, transcriptome data
Ileal Crohn's disease classification
时间窗: surgery time, Time 0
Ileal Crohn's disease classification will be performed using data integration (taking into account clinical data, immunological, genetic, microbiota, transcriptome data). A molecular classification will be possible due to this data integration analysis
次要结局
未报告次要终点
研究者
Madeleine Bezault
Pr Matthieu Allez
Saint-Louis Hospital, Paris, France