Pilot Study of a New Technique of Oral Fecal Transplantation Using Frozen Stool Capsules for the Maintenance Treatment of Pediatric Ulcerative Colitis.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 26
- 试验地点
- 6
- 主要终点
- Success of FMT with frozen stool capsules defined by an increase in the richness of the recipient's microbiota at 6 months.
研究概览
简要总结
The purpose of this study is to evaluate whether FMT by frozen stool capsules in pediatric UC patients in remission after corticosteroid treatment, can modify their dysbiotic gut microbiota by increasing the richness of their microbiota at 6 months.
详细描述
Ulcerative colitis (UC) is characterized by chronic inflammation of the colon of undetermined origin. Their incidence is increasing dramatically in the paediatric population.
Pediatric-onset inflammatory bowel disease (IBD) is characterized by a greater severity than adult IBD. Although great progress has been made in recent years, the pathogenesis of IBD is not fully elucidated. During UC, an imbalance in the composition of gut microbiota, called "dysbiosis", has been identified. This dysbiosis is notably characterized by an increased proportion of pro-inflammatory microorganisms and a decreased proportion of anti-inflammatory microorganisms. The current treatments used in IBD mainly target the immune system through immunosuppressants, and help to shorten flairs and prevent recurrences, but there is no curative treatment.
From a therapeutic point of view, the correction of this dysbiosis is thus an attractive approach. Until now, efficacy of microbiome-based therapies such as probiotics or antibiotics has been disappointing in IBD. Fecal microbiota transplantation (FMT) consists of the administration of fecal material from a donor into the intestinal tract of a recipient to change their microbiota composition and restore healthy conditions. FMT has been successfully used for many years for the treatment of Clostridioides difficile infection. Recent studies seem to show a benefit of FMT in UC.
The investigator's main hypothesis is that the replacement of a dysbiotic microbiota by a 'healthy' microbiota by FMT can modify the richness of UC patient's microbiota and has a positive impact on the disease course.
Once steroid-induced remission will be achieved, patients will be included and randomised to receive either FMT by frozen stool capsules or enemas. They will receive 3 doses at 0, 1 and 2 months. They will be followed for one year with stool samples collected every 3 months. Clinical and laboratory data will be collected.
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
- None
入排标准
- 年龄范围
- 8 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for patients:
- •Patient aged 8 to 17 years old
- •Ulcerative colitis (UC), whatever the extent, except isolated proctitis (<5 cm), diagnosed for more than 3 months according to the usual clinical, biological and endoscopic criteria
- •Moderate active UC defined by a PUCAI score > 35 and responding to corticosteroid treatment with a PUCAI score <10 at enrollment
- •Treatment of UC (5-ASA, immunosuppressants, biotherapies) stable for more than 3 months
- •Patient able to swallow test capsules
- •For girls of childbearing age:
- •To have a negative blood (or urine) pregnancy test
- •To agree to use a reliable contraceptive method from visit 1 until the end of the research
- •Patient with health insurance
- •Informed written consent form signed by both parents or by the person (s) with parental authority
排除标准
- •for patients:
- •isolated proctitis (<5 cm)
- •Being on enteral nutrition
- •Have received antibiotic or antifungal treatment in the 4 weeks prior to enrollment
- •Having a Clostridioides difficile infection in the 4 weeks prior to enrollment;
- •Being pregnant or breastfeeding, or have a positive pregnancy test;
- •Have a contraindication to colonoscopy or general anaesthesia
研究组 & 干预措施
Fecal Microbiota Transplantation by enema
Patients receiving fecal microbiota transplantation from a healthy donor in 3 times after inclusion and randomisation (Month 0 - Month 1 - Month 2) using frozen stool enemas.
干预措施: Fecal Microbiota Transplantation by Intra-rectal enemas (Drug)
Fecal Microbiota Transplantation by Stool capsules
Patients receiving fecal microbiota transplantation from a healthy donor in 3 times after inclusion and randomisation (Month 0 - Month 1 - Month 2) using frozen stool capsules
干预措施: Fecal Microbiota Transplantation by Stool capsules (Drug)
结局指标
主要结局
Success of FMT with frozen stool capsules defined by an increase in the richness of the recipient's microbiota at 6 months.
时间窗: 6 months after the first Fecal Microbiota Transplantation (FMT)
Success of FMT is defined by an increase in the richness of the recipient's microbiota at 6 months. Microbiota richness will be evaluated by measuring the alpha diversity of the microbiota using Shannon index. The success of the FMT will be defined by an increase in the Shannon index of 0.5 points between the recipient microbiota at M0 and the recipient microbiota at M6.
次要结局
- Success of FMT by stool enema defined by an increase in the richness of the recipient's microbiota at 6 and 12 months(6 and 12 months after the first FMT)
- Success of FMT with frozen stool capsules on the change of recipient dysbiotic microbiota at 6 and 12 months(6 and 12 months after the first FMT)
- Success of FMT with frozen stool capsules on the richness and change of mucosal microbiota at 12 months(12 months)
- Ulcerative colitis clinical relapse(6 and 12 months)
- Success of FMT by enema on the change of recipient dysbiotic microbiota at 6 and 12 months(6 and 12 months after the first FMT)
- Success of FMT by enema on the change of mucosal recipient dysbiotic microbiota at 6 and 12 months(6 and 12 months after the first FMT)
- FMT with frozen stool capsules Feasibility(At inclusion, 1 and 2 months after each FMT)
- Change of patient's quality of life evaluated with IMPACT-3 questionnaire from inclusion until 12 months(At inclusion 2, 6, 9 and 12 months)
- Change of inflammatory blood markers from baseline to 12 months(At inclusion, 6, 9 and 12 months)
- Success of FMT with frozen stool capsules defined by an increase in the richness of the recipient's microbiota at 12 months(12 months after the first FMT)
- Success of FMT by enema on the richness and change of mucosal microbiota at 12 months(12 months)
- Success of FMT with frozen stool capsules on the change of mucosal recipient dysbiotic microbiota at 6 and 12 months(6 and 12 months after the first FMT)
- FMT by enema Feasibility(At inclusion, 1 and 2 months after each FMT)
- Ulcerative colitis Endoscopic relapse(12 months)
- Change of faecal calprotectin from baseline to 12 months(At inclusion, 6, 9 and 12 months)
- Incidence of adverse events(26 months)