The purpose of this research study is to assess the safety and efficacy of fecal microbiota transplant (FMT) in the treatment of chronic pouchitis.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
The intervention consists of the following steps: * Step 1: Vancomycin 125 mg orally every 6 hours and metronidazole 250 mg orally every 6 hours for 5 days. * Step 2: Bowel preparation with 10 ounces of magnesium citrate. * Step 3: Two FMT doses will be administered via enema one week apart using stool from donors with a durably healthy pouch.
Icahn School of Medicine at Mount Sinai
New York, New York, United States
RECRUITINGNumber of patients with FMT related adverse events
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.
Time frame: 8 weeks
Number of patients in clinical remission
The number of patients in clinical remission assessed via patient interview and defined as mPDAI clinical subscore ≤4 points and no need for antibiotic therapy at week 8.
Time frame: 8 weeks
Number of patients with endoscopic response
The number of patients with endoscopic response assessed via pouchoscopy and defined as a decrease from baseline in mPDAI endoscopic subscore \> 2 points at week 8.
Time frame: 8 weeks
Change in recipient fecal microbial diversity via metagenomics analysis
The change in recipient fecal microbial diversity after FMT relative to baseline assessed via stool collection and using metagenomics analysis.
Time frame: Baseline and up to 8 weeks
Change in recipient fecal microbial diversity via strain strain isolation
The change in recipient fecal microbial diversity after FMT relative to baseline assessed via strain isolation - to isolate and sequence the gut microbial strains from each donor
Time frame: Baseline and up to 8 weeks
Change in recipient microbe tracking
The change in recipient fecal microbial diversity after FMT relative to baseline assessed by recipient microbe tracking.
Time frame: Baseline and up to 8 weeks
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Change in B cells
The change in the mucosal immune profile before and after FMT as measured by B cells
Time frame: Baseline and 8 weeks
Change in myeloid cells
The change in the mucosal immune profile before and after FMT as measured by myeloid cells
Time frame: Baseline and 8 weeks
Change in T cells
The change in the mucosal immune profile before and after FMT as measured by T cells
Time frame: Baseline and 8 weeks
Change in NK cell subsets
The change in the mucosal immune profile before and after FMT as measured by NK cell subsets
Time frame: Baseline and 8 weeks