Fecal Microbiota Transplant for Patients With Chronic Pouchitis

Study Overview
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Brief Summary
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The purpose of this research study is to assess the safety and efficacy of fecal microbiota transplant (FMT) in the treatment of chronic pouchitis.

Detailed Description
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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.

Official Title
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Safety and Efficacy of Healthy to Inflamed Pouch Fecal Microbiota Transplantation

Conditions
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Chronic Pouchitis, Pouchitis

Intervention / Treatment
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* Drug: Fecal Microbiota Transplant (FMT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients age 18 or greater with UC who have undergone restorative proctocolectomy with ileal pouch anal anastomosis and have: Chronic antibiotic dependent pouchitis: 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 Exclusion Criteria: 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 Subjects 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 subject at greater risk from FMT

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This will be a pilot study of 16-18 patients who will each receive FMT.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fecal Microbiota Transplant (FMT)<br>Single arm of 16-18 subjects, all of whom will receive the interventional FMT. | Drug: Fecal Microbiota Transplant (FMT)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number 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. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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 | 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. | Baseline and up to 8 weeks | 
| Change in B cells | The change in the mucosal immune profile before and after FMT as measured by B cells | Baseline and 8 weeks | 
| Change in myeloid cells | The change in the mucosal immune profile before and after FMT as measured by myeloid cells | Baseline and 8 weeks | 
| Change in T cells | The change in the mucosal immune profile before and after FMT as measured by T cells | 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 | Baseline and 8 weeks |