Safety and Efficacy of Fecal Microbiome Transplantation (FMT) in the Treatment of Antibiotic Dependent Pouchitis (ADP)
Safety and Efficacy of Fecal Microbiome Transplantation (FMT) in the Treatment of Antibiotic Dependent Pouchitis (ADP)
Antibiotic dependent pouchitis (ADP) is predestined to benefit from FMT, since bacterial
 dysbiosis, which can only be controlled with antibiotics, appears to be the major driver of
 the clinical symptoms. This is a proof of concept randomized placebo controlled trial, in
 which 50% of the patients will receive FMT and 50% will receive a placebo FMT. Additionally
 the trial offers an open label extension period.
FMT for ADP is a promising approach, given the documented role of bacteria in the
 pathogenesis. In contrast to patients with C. difficile colitis, in whom a single FMT is
 highly effective, in patients with Inflammatory Bowel Disease (IBD) an intensified therapy
 with daily or repeated FMT may be more beneficial. Whereas repeated endoscopic application
 are not feasible and repeated enema applications are not favored by patients a combination of
 endoscopic FMT and consecutive maintenance therapy with oral FMT using the FMT capsule G3
 produced by OpenBiome to help establish the donor microbiome in the host seems to be the most
 promising approach. The objective of this trial is to evaluate the safety of FMT in patients
 with ADP and to estimate the effect size to be achieved from FMT therapy in patients with ADP
 for subsequent evaluation in a large definitive trial. A secondary objective is to study the
 microbial engraftment of donor FMT in the recipients.

 This proof of concept randomized placebo controlled trial with an open label extension period
 will evaluate the safety and efficacy of an initial endoscopic FMT followed by 14 days of
 oral FMT. The study has two distinct outcomes, a clinical and translational aim, to
 investigate the effect of FMT in patients with ADP.

 Aim1: Evaluation of safety, tolerability and clinical effectiveness (measured as clinical
 response or remission and discontinuation of antibiotic therapy) of FMT in patients with ADP.

 Aim 2: Evaluation of the impact of FMT on the fecal bacterial microbiome in patients with
 ADP, which will provide functional data about possible mechanisms of this therapy.
Inclusion Criteria:

 -  Signed informed consent.

 -  Man or woman between 18 and 70 years of age.

 -  Ileal Pouch-Anal Anastomosis (IPAA) after colectomy for ulcerative colitis

 -  Active pouchitis, defined as a modified pouch disease activity index (mPDAI) ≥ 5 and a
 history of ≥ 4 antibiotic therapies for pouchitis in the last 12 months

 or

 - Need for ongoing 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.

 Exclusion Criteria:

 -  Treatment with biologics (e.g. infliximab, adalimumab, golimumab, vedolizumab)

 -  Treatment with immunomodulators (azathioprine, 6-mercaptopurine (6-MP), methotrexate),
 steroids or any investigational drugs

 -  Use of cholestyramine

 -  Crohn's disease of the pouch

 -  Known cytomegalovirus infection of the pouch

 -  Clostridium difficile infection

 -  Isolated cuffitis

 -  Clinical significant strictures of the pouch inlet or outlet

 -  Concurrent intestinal obstruction

 -  History of familial adenomatous polyposis

 -  History of uncontrolled lactose intolerance

 -  History of confirmed (serological test and/or histology) celiac disease

 -  Pregnancy, breast feeding, or planning to become pregnant during the trial

 -  Non - steroidal inflammatory medications (NSAIDs) as long-term treatment, defined as
 use for at least 4 days a week each month

 -  Dysphagia (oropharyngeal, esophageal, functional, neuromuscular)

 -  History of recurrent aspiration episodes

 -  Proven Gastroparesis

 -  Allergy to the following generally regarded as safe ingredients (GRAS): glycerol, acid
 resistant hypromellose (HPMC), gellan gum, cocoa butter, titanium dioxide

 -  Adverse event attributable to previous FMT

 -  Allergy/intolerance to pump inhibitor therapy

 -  Any condition for which the investigator thinks the FMT treatment may pose a health
 risk (e.g. severely immunocompromised)

 -  Participation in another clinical trial within the last 30 days, simultaneous
 participation in another clinical trial, or previous participation in this trial

 -  During the trial period until one week after the trial end: Non-use of appropriate
 contraceptives in females of childbearing potential (e.g. condoms, intrauterine device
 (IUD), hormonal contraception, or other means considered adequate by the responsible
 investigator) or in males with a child-fathering potential (condoms, or other means
 considered adequate by the responsible investigator during treatment - Well-founded
 doubt about the patient's cooperation