Clinical trial NCT05829109: Fecal Microbiota Transplant for Patients With Chronic Pouchitis
Official title: Safety and Efficacy of Healthy to Inflamed Pouch Fecal Microbiota Transplantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Chronic Pouchitis
Pouchitis
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2023-04-25
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This will be a pilot study of 16-18 patients who will each receive FMT.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with FMT related adverse events
timeFrame: 8 weeks
Secondary outcomes:
measure: Number of patients in clinical remission
timeFrame: 8 weeks
measure: Number of patients with endoscopic response
timeFrame: 8 weeks
measure: Change in recipient fecal microbial diversity via metagenomics analysis
timeFrame: Baseline and up to 8 weeks
measure: Change in recipient fecal microbial diversity via strain strain isolation
timeFrame: Baseline and up to 8 weeks
measure: Change in recipient microbe tracking
timeFrame: Baseline and up to 8 weeks
measure: Change in B cells
timeFrame: Baseline and 8 weeks
measure: Change in myeloid cells
timeFrame: Baseline and 8 weeks
measure: Change in T cells
timeFrame: Baseline and 8 weeks
measure: Change in NK cell subsets
timeFrame: Baseline and 8 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Maia Kayal, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: