Safety and Efficacy of Healthy to Inflamed Pouch Fecal Microbiota Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Number of patients with FMT related adverse events
研究概览
简要总结
The purpose of this research study is to assess the safety and efficacy of fecal microbiota transplant (FMT) in the treatment of chronic pouchitis.
详细描述
The purpose of this research study is to assess the safety and efficacy of fecal microbiota transplant (FMT) in the treatment of chronic pouchitis. FMT has been successfully used in the treatment of recurrent Clostridiodes difficile infection and has shown benefit in the treatment of ulcerative colitis in clinical trials. The success of FMT in these patients is because of the reconstitution of the recipient's unhealthy gut bacteria with the donor's healthy gut bacteria.
Surgery to remove the colon is required in a subset of patients with ulcerative colitis that does not respond to medical therapy. In these patients, an internal pouch is created from small intestine to function as a stool reservoir and avoid an ostomy after the colon is removed. Inflammation of the pouch, pouchitis, is common after surgery and can manifest as diarrhea, pelvic pain, urgency and blood in the stool. Chronic pouchitis occurs in up to 20% of patients and there is no approved treatment. A number of studies have evaluated FMT in patients with chronic pouchitis, but have proven unsuccessful. This is likely because these studies have used stool from patients with a colon and transplanted it into patients with a pouch. This is problematic because the gut bacteria of the colon and pouch are not similar, and putting healthy stool from a colon may not reconstitute a healthy pouch microbiome. The specific purpose of this project is to transplant stool from patients with a healthy pouch to patients with an inflamed pouch.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients age 18 or greater with UC who have undergone TPC with IPAA and have one of the following chronic pouchitis phenotypes, each defined as:
- •Chronic antibiotic dependent pouchitis:
- •The need for continuous antibiotic therapy (>4 weeks) to maintain clinical remission and a history of at least 2 attempts in the last 24 months to stop antibiotic therapy resulting in pouchitis episodes, OR
- •Active pouchitis with a modified Pouchitis Disease Activity Index (mPDAI) ≥5 and a history of ≥4 antibiotic therapies in the last 12 months
- •Chronic antibiotic refractory pouchitis:
- •Active pouchitis with a modified Pouchitis Disease Activity Index (mPDAI) ≥5 with no response to antibiotics
- •Crohn's disease like pouch inflammation on biologic or small molecule therapy with persistent symptoms:
- •Pre-pouch ileal inflammation, strictures, and/or fistulae, AND
- •Active biologic or small molecule therapy, AND
- •Persistent symptoms with mPDAI clinical sub-score ≥ 2
排除标准
- •Patients with UC who underwent TPC with IPAA and meet one of the following criteria will be excluded:
- •Allergy to vancomycin, metronidazole, or ingredients present in the FMT
- •Women who are breastfeeding
- •Women who are pregnant
- •Participants with fever > 100.4F/38C or other signs of active illness
- •Active treatment with biologics (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab)
- •Active treatment with immunomodulators (azathioprine, 6-mercaptopurine, methotrexate), steroids or any investigational drugs
- •Crohn's disease like pouch inflammation
- •Active enteric infection
- •Isolated cuffitis
- •Clinically significant strictures of the pouch inlet or outlet
- •Participation in a clinical trial in the preceding 30 days
- •Any condition that the physician investigators deems unsafe, including other conditions or medications that the investigator determines will put the participant at greater risk from FMT
研究组 & 干预措施
Fecal Microbiota Transplant (FMT)
Single arm of 16-18 subjects, all of whom will receive the interventional FMT.
干预措施: Fecal Microbiota Transplant (FMT) (Drug)
结局指标
主要结局
Number of patients with FMT related adverse events
时间窗: 8 weeks
The number of patients with FMT related adverse events through week 8 classified according to the Medical Dictionary for Regulatory Activities (MedDRA) and categorized according to the NIH Criteria for Adverse Events.
次要结局
- Number of patients in clinical remission(8 weeks)
- Change in recipient fecal microbial diversity via strain strain isolation(Baseline and up to 8 weeks)
- Number of patients with endoscopic response(8 weeks)
- Change in recipient microbe tracking(Baseline and up to 8 weeks)
- Change in NK cell subsets(Baseline and 8 weeks)
- Change in recipient fecal microbial diversity via metagenomics analysis(Baseline and up to 8 weeks)
- Change in B cells(Baseline and 8 weeks)
- Change in T cells(Baseline and 8 weeks)
- Change in myeloid cells(Baseline and 8 weeks)
研究者
Maia Kayal
Assistant Professor
Icahn School of Medicine at Mount Sinai