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

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ClinicalTrials.gov Identifier: NCT02782325
Recruitment Status : Active, not recruiting
First Posted : May 25, 2016
Last Update Posted : July 13, 2018
Sponsor:
Collaborators:
OpenBiome
Crohn's and Colitis Foundation
The Broad Foundation
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

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.

Condition or disease Intervention/treatment Phase
Pouchitis Biological: Fecal microbiota transplantation Biological: Open Label FMT - Extension phase Biological: Placebo Phase 1 Phase 2

Detailed Description:

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Fecal Microbiome Transplantation (FMT) in the Treatment of Antibiotic Dependent Pouchitis (ADP)
Actual Study Start Date : June 1, 2017
Estimated Primary Completion Date : June 1, 2019
Estimated Study Completion Date : January 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Fecal Microbiota Transplantation (FMT)
Endoscopic application of OpenBiome FMT Lower Delivery followed by 2 weeks of treatment with OpenBiome FMT Capsules G3
Biological: Fecal microbiota transplantation
Endoscopic FMT followed by 2 weeks of oral FMT with evaluation of primary and secondary endpoints at week 4, 8 and 16.
Other Name: FMT

Placebo Comparator: Placebo Transplantation (FMT)
Endoscopic application of placebo FMT followed by 2 weeks of treatment with placebo Capsules G3
Biological: Placebo
Endoscopic placebo FMT followed by 2 weeks of oral placebo FMT with evaluation of primary and secondary endpoints at week 4, 8 and 16.

Active Comparator: Open Label FMT - Extension phase
In case the study patient does not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study he/she will be offered the possibility to participate in open label extension with an additional endoscopic FMT followed by 2 weeks of oral FMT and clinical follow up at week 10, 14 and 22.
Biological: Open Label FMT - Extension phase
In case the study patient does not achieve clinical remission at week 4 or experiences a flare of disease on day 15-28 after start of the study he/she will be offered the possibility to participate in open label extension with an additional endoscopic FMT followed by 2 weeks of oral FMT and clinical follow up at week 10, 14 and 22.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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 no need for antibiotic therapy at week 4.

  2. 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 no need for antibiotic therapy at week 16.

  3. 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.

  4. Clinical Response in patients with active pouchitis at 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.

  5. Clinical Response in patients with active pouchitis 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.

  6. Clinical Response in patients with active pouchitis 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.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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-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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02782325


Locations
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
OpenBiome
Crohn's and Colitis Foundation
The Broad Foundation
Investigators
Principal Investigator: Hans Herfarth, MD, PhD University of North Carolina

Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02782325     History of Changes
Other Study ID Numbers: 16-1310
FMTADP ( Other Identifier: UNC-CH )
First Posted: May 25, 2016    Key Record Dates
Last Update Posted: July 13, 2018
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The final results of the trial will be posted on clinical trials.gov. No individual patient data will be posted.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Pouchitis
Ileitis
Enteritis
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Ileal Diseases
Anti-Bacterial Agents
Anti-Infective Agents