Impact of Fecal Microbiota Transplantation in Ulcerative Colitis: a Randomized, Sham Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Steroid-free clinical and endoscopic remission
研究概览
简要总结
Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. UC pathogenesis remains poorly understood but involves an inappropriate immune response toward an unbalanced gut microbiota (called dysbiosis) in predisposed hosts.
The purpose of this study is to determine the effect of the fecal microbiota transplantation on UC.
详细描述
Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease affecting approximately 90 000 patients in France, mostly at young age, and altering their quality of life.
Conventional Immunosuppressive treatment (ie azathioprine, anti-TNF (tumor necrosis factor ), vedolizumab) used in UC are expensive and associated with potentially severe complications such as infections and cancers.
UC pathogenesis remains poorly understood but involves an inappropriate immune response toward an unbalanced gut microbiota (called dysbiosis) in predisposed hosts.
Fecal microbiota transplantation (FMT) is now recommended in guidelines for treating recurrent Clostridium difficile infection. Although the pathogenesis involved in UC is different, FMT is a potential therapeutic strategy as transferring a healthy microbiota in an UC patient could restore the appropriate host-microbiota crosstalk.
As the gut microbiota is dramatically altered by intestinal inflammation, transferring a massive amount of microbial organisms in an inflamed gut with epithelial barrier disruption might be a suboptimal strategy and could even have detrimental effects by allowing bacterial translocation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion Criteria for patients :
- •Age ≥ 18 years and < 75 years
- •Ulcerative colitis (according to the Lennard Jones criteria) diagnosed for at least 3 months and :
- •Currently active (PMC > 1) and planned to be treated by systemic corticosteroids (minimum 40mg prednisone equivalent daily) Or
- •Currently treated by systemic corticosteroid (minimum 40 mg prednisone equivalent daily) within max 3 weeks Or
- •Steroid dependent patients (at least one unsuccessful attempt to discontinue steroid within the last 6 months before inclusion)
- •Patient with health insurance (AME excepted)
- •Informed written consent
- •Female of child-bearing age with an active contraception and this during at least period of treatment until the end of active follow-up period (week 24)
- •Inclusion Criteria for healthy volunteers donors :
- •Age ≥ 18 years and < 50 years
- •17 kg/m² < body mass index < 30 kg/m²
- •Regular bowel movement defined as at least 1 stool every other day and maximum 2 stools per day
- •Subject with health insurance (AME excepted)
- •Informed Written consent
排除标准
- •Exclusion Criteria for patients :
- •UC complication requiring surgical treatment
- •Patient treated with high dose corticosteroid more than three weeks before inclusion (≥ 40 mg prednisone equivalent daily) except in case of steroid-dependence
- •Contraindication to colonoscopy or anesthesia
- •Pregnancy or breastfeeding during the study
- •Treatment preceding the colonoscopy with:
- •intravenous infliximab and/or vedolizumab and/or ustekinumab (< 6 weeks before the planned date of the colonoscopy) and/or subcutaneous infliximab (<2 weeks before the planned date of the colonoscopy), and /or adalimumab (<2 weeks before the planned date of the colonoscopy) and/or golimumab and/or tofacitinib (<4 weeks before the planned date of the colonoscopy)
- •immunosuppressant (thiopurine, methotrexate, tacrolimus or other classical immunosuppressant) started or stopped < 3 months before the planned date of the colonoscopy
- •Antibiotics, antifungic or probiotics treatment < 4 weeks before the planned date of the colonoscopy
- •participation in any other interventional study
- •patient under legal protection
- •Exclusion Criteria for healthy volunteers donors :
- •- For details, please see protocol.
研究组 & 干预措施
Group B - fecal microbiota transplantation
Patients receiving the fecal microbiota transplantation (FMT) in 3 times after inclusion and randomisation
干预措施: Fecal Microbiota Transplantation (FMT) (Drug)
Group A- Sham-transplantation
Patients receiving the sham-transplantation in 3 times after inclusion and randomisation
干预措施: Sham-transplantation Placebo (Drug)
结局指标
主要结局
Steroid-free clinical and endoscopic remission
时间窗: 12 weeks after FMT or sham-transplantation
Steroid-free clinical and endoscopic remission defined as a total Mayo score of 2 or lower and no subscore higher than 1 and mucosal healing defined as an endoscopic subscore of 0 or 1 (Sigmoidoscopy).
次要结局
- Steroid-free clinical remission(24 weeks after FMT or sham-transplantation)
- Steroid-free endoscopic response(12 weeks after FMTor sham-transplantation)
- Steroid-free endoscopic remission(12 weeks after FMT or sham-transplantation)
- Microbiota composition and diversity(12 and 24 weeks after FMT or sham-transplantation)
- Proportion of adverse events in each group(Through study completion, up to 25 months and one week)
- Inflammatory biological parameter 1(up to 24 weeks)
- Inflammatory biological parameter 2(up to 24 weeks)
- Inflammatory biological parameter 3(up to 24 weeks)
- Endoscopic lesions(12 weeks after FMT or sham-transplantation)
- Steroid-free clinical remission(12 weeks after FMT or sham-transplantation)