Clinical Trial: Safety and Efficacy of Fecal Microbiome Transplantation (FMT) in the Treatment of Antibiotic Dependent Pouchitis (ADP)

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Safety and Efficacy of Fecal Microbiome Transplantation (FMT) in the Treatment of Antibiotic Dependent Pouchitis (ADP)

Brief Summary: 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.

Detailed Summary:

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.


Sponsor: University of North Carolina, Chapel Hill

Current Primary Outcome: Incidence of Treatment Emergent Adverse Events [ Time Frame: 16 weeks in the randomized placebo controlled study segment and 22 weeks in the open label FMT extension segment ]

Number of patients with FMT related adverse event (classified according to MEDRAS LLT; lowest level term) and categorized according to CTCAE Version 4.0. The safety will be assessed in the randomized placebo controlled segment of the study over 16 weeks and if the patient should enter the open label extension part of the study over 22 weeks.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Clinical Remission week 4 [ Time Frame: Week 4 ]
    Clinical remission as defined by a composite assessment, of which all criteria need to be met: Clinical mPDAI score ≤4 points and decrease from the baseline mPDAI > 2 points and no need for antibiotic therapy at week 4.
  • Clinical remission week 16 [ Time Frame: Week 16 ]
    Clinical remission as defined by a composite assessment, of which all criteria need to be met: Clinical mPDAI score ≤4 points and decrease from the baseline mPDAI > 2 points and no need for antibiotic therapy at week 16.
  • Endoscopic improvement week 4 [ Time Frame: Week 4 ]
    Endoscopic improvement of active pouchitis (decrease from baseline in mPDAI endoscopic subscore > 2 points) at week 4.
  • Clinical Response week 4 [ Time Frame: Week 4 ]
    Response as defined by a composite assessment of which both criteria has to be met: Decrease from baseline mPDAI clinical subscore > 2 points and no need for antibiotic therapy at week 4.
  • Clinical Response week 8 [ Time Frame: Week 8 ]
    Response as defined by a composite assessment of which both criteria has to be met: Decrease from baseline mPDAI clinical subscore > 2 points and no need for antibiotic therapy at week 8.
  • Clinical Response week 16 [ Time Frame: Week 16 ]
    Response as defined by a composite assessment of which both criteria has to be met: Decrease from baseline mPDAI clinical subscore > 2 points and no need for antibiotic therapy at week 16.


Original Secondary Outcome: Same as current

Information By: University of North Carolina, Chapel Hill

Dates:
Date Received: May 12, 2016
Date Started: April 2017
Date Completion: January 2020
Last Updated: March 20, 2017
Last Verified: March 2017