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

Primary Purpose

Pouchitis

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Active FMT, then open label FMT
Placebo FMT, then open label FMT
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pouchitis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of North Carolina

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Active FMT, then open label FMT

Placebo FMT, then open label FMT

Arm Description

Endoscopic application of OpenBiome FMT Lower Delivery followed by 2 weeks of treatment with OpenBiome FMT Capsules G3 with follow-up at week 4, 8, 16 and 24 after inclusion. 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 after at least 10 day of antibiotic therapy with an additional endoscopic FMT followed by 2 weeks of oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT.

Endoscopic application of Placebo FMT Lower Delivery followed by 2 weeks of treatment with Placebo FMT Capsules G3 with follow-up at week 4, 8, 16 and 24 after inclusion. 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 after at least 10 day of antibiotic therapy with an additional endoscopic FMT followed by 2 weeks of oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT.

Outcomes

Primary Outcome Measures

Number of Patients With FMT Related Adverse Event
Number of patients with FMT related adverse event (classified according to MedDRA; lowest level term) and categorized according to CTCAE Version 4.0. The safety was assessed in the randomized placebo controlled segment of the study over 24 weeks after initial endoscopic FMT weeks and if the patient should enter the open label extension part of the study also for 24 weeks after initial open label FMT. 6 patients participated in the randomized arm and 5 patients in the open label extension arm.

Secondary Outcome Measures

Number of Patients in Clinical Remission Week 4 After Endoscopic and Oral FMT
Clinical remission as defined by a composite assessment, of which all criteria need to be met: Clinical modified pouch diseases activity index (mPDAI) score ≤4 points and no need for antibiotic therapy at week 4.
Number of Patients in Clinical Remission 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.
Number of Patients With Endoscopic Improvement Week 4 After Endoscopic and Oral FMT
Endoscopic improvement of active pouchitis (decrease from baseline in modified pouch disease activity index endoscopic subscore > 2 points) at week 4.
Number of Patients With Clinical Response at Week 4 in Patients Entering the Trial With Active Pouchitis Symptoms
This outcome measure is for patients with active pouchitis symptoms entering the trial. Since all patients entered with inactive pouchitis no patient could be evaluated for this outcome. 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.
Number of Patients With Clinical Response Week 8 and Active Pouchitis at Baseline
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 of the randomized phase.
Number of Patients With Clinical Response i at Week 16 and Active Pouchitis at Baseline
This outcome measure is for patients with active pouchitis symptoms entering the trial. 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.

Full Information

First Posted
May 12, 2016
Last Updated
April 23, 2019
Sponsor
University of North Carolina, Chapel Hill
Collaborators
OpenBiome, Crohn's and Colitis Foundation, The Broad Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT02782325
Brief Title
Safety and Efficacy of Fecal Microbiome Transplantation (FMT) in the Treatment of Antibiotic Dependent Pouchitis (ADP)
Official Title
Safety and Efficacy of Fecal Microbiome Transplantation (FMT) in the Treatment of Antibiotic Dependent Pouchitis (ADP)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Terminated
Why Stopped
Due low efficacy of FMT in interim analysis.
Study Start Date
June 1, 2017 (Actual)
Primary Completion Date
December 3, 2018 (Actual)
Study Completion Date
December 3, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
OpenBiome, Crohn's and Colitis Foundation, The Broad Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pouchitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active FMT, then open label FMT
Arm Type
Active Comparator
Arm Description
Endoscopic application of OpenBiome FMT Lower Delivery followed by 2 weeks of treatment with OpenBiome FMT Capsules G3 with follow-up at week 4, 8, 16 and 24 after inclusion. 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 after at least 10 day of antibiotic therapy with an additional endoscopic FMT followed by 2 weeks of oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT.
Arm Title
Placebo FMT, then open label FMT
Arm Type
Placebo Comparator
Arm Description
Endoscopic application of Placebo FMT Lower Delivery followed by 2 weeks of treatment with Placebo FMT Capsules G3 with follow-up at week 4, 8, 16 and 24 after inclusion. 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 after at least 10 day of antibiotic therapy with an additional endoscopic FMT followed by 2 weeks of oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT.
Intervention Type
Biological
Intervention Name(s)
Active FMT, then open label FMT
Other Intervention Name(s)
Active FMT
Intervention Description
Endoscopic application of OpenBiome FMT Lower Delivery followed by 2 weeks of treatment with OpenBiome FMT Capsules G3 with follow-up at week 4, 8, 16 and 24 after inclusion. 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 after at least 10 day of antibiotic therapy with an additional endoscopic FMT followed by 2 weeks of oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT.
Intervention Type
Biological
Intervention Name(s)
Placebo FMT, then open label FMT
Other Intervention Name(s)
Placebo FMT
Intervention Description
Endoscopic application of Placebo FMT Lower Delivery followed by 2 weeks of treatment with Placebo FMT Capsules G3 with follow-up at week 4, 8, 16 and 24 after inclusion. 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 after at least 10 day of antibiotic therapy with an additional endoscopic FMT followed by 2 weeks of oral FMT. Follow-up will occur in open label at week 4, 8, 16 and 24 after open label FMT.
Primary Outcome Measure Information:
Title
Number of Patients With FMT Related Adverse Event
Description
Number of patients with FMT related adverse event (classified according to MedDRA; lowest level term) and categorized according to CTCAE Version 4.0. The safety was assessed in the randomized placebo controlled segment of the study over 24 weeks after initial endoscopic FMT weeks and if the patient should enter the open label extension part of the study also for 24 weeks after initial open label FMT. 6 patients participated in the randomized arm and 5 patients in the open label extension arm.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Number of Patients in Clinical Remission Week 4 After Endoscopic and Oral FMT
Description
Clinical remission as defined by a composite assessment, of which all criteria need to be met: Clinical modified pouch diseases activity index (mPDAI) score ≤4 points and no need for antibiotic therapy at week 4.
Time Frame
4 weeks
Title
Number of Patients in Clinical Remission Week 16
Description
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.
Time Frame
16 weeks
Title
Number of Patients With Endoscopic Improvement Week 4 After Endoscopic and Oral FMT
Description
Endoscopic improvement of active pouchitis (decrease from baseline in modified pouch disease activity index endoscopic subscore > 2 points) at week 4.
Time Frame
4 weeks
Title
Number of Patients With Clinical Response at Week 4 in Patients Entering the Trial With Active Pouchitis Symptoms
Description
This outcome measure is for patients with active pouchitis symptoms entering the trial. Since all patients entered with inactive pouchitis no patient could be evaluated for this outcome. 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.
Time Frame
4 weeks
Title
Number of Patients With Clinical Response Week 8 and Active Pouchitis at Baseline
Description
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 of the randomized phase.
Time Frame
8 weeks
Title
Number of Patients With Clinical Response i at Week 16 and Active Pouchitis at Baseline
Description
This outcome measure is for patients with active pouchitis symptoms entering the trial. 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.
Time Frame
16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hans Herfarth, MD, PhD
Organizational Affiliation
University of North Carolina
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
The final results of the trial will be posted on clinical trials.gov. No individual patient data will be posted.

Learn more about this trial

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

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