Fecal Microbiota Transplant for Patients With Chronic Pouchitis

Официальное название

Safety and Efficacy of Healthy to Inflamed Pouch Fecal Microbiota Transplantation

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат Fecal Microbiota Transplant (FMT)
  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.

Первичные конечные точки

• Number of patients with FMT related adverse events [Срок оценки: 8 weeks]

Вторичные конечные точки (9)

• Number of patients in clinical remission [Срок оценки: 8 weeks]
• Number of patients with endoscopic response [Срок оценки: 8 weeks]
• Change in recipient fecal microbial diversity via metagenomics analysis [Срок оценки: Baseline and up to 8 weeks]
• Change in recipient fecal microbial diversity via strain strain isolation [Срок оценки: Baseline and up to 8 weeks]
• Change in recipient microbe tracking [Срок оценки: Baseline and up to 8 weeks]
• Change in B cells [Срок оценки: Baseline and 8 weeks]
• Change in myeloid cells [Срок оценки: Baseline and 8 weeks]
• Change in T cells [Срок оценки: Baseline and 8 weeks]
• Change in NK cell subsets [Срок оценки: Baseline and 8 weeks]

Критерии участия

Критерии включения

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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Icahn School of Medicine at Mount Sinai — New York

Идентификаторы

NCT: NCT05829109 · STUDY-22-01753

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗