PouchitisPhase 1/2NCT02782325
Safety and Efficacy of Fecal Microbiome Transplantation (FMT) in the Treatment of Antibiotic Dependent Pouchitis (ADP)
A Phase 1/2 study testing Active FMT, then open label FMT in people with Pouchitis, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pouchitis
- What is being tested?
- Active FMT, then open label FMT
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2017to 3 Dec 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 23Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina
Chapel Hill, North Carolina, 27599
About this study
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.
Read the 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.
- Conditions
- Pouchitis
- Being tested
- Active FMT, then open label FMT, Placebo FMT, then open label FMT
- Medical subject headings
- Pouchitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active FMT, then open label FMTBiological
Also called Active FMT
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.
Placebo FMT, then open label FMTBiological
Also called Placebo 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.
| Study group | Role | What they receive |
|---|---|---|
| Active FMT, then open label FMT | Active comparator | 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. Receives: Biological: Active FMT, then open label FMT |
| Placebo FMT, then open label FMT | Placebo comparator | 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. Receives: Biological: Placebo FMT, then open label FMT |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 weeks
Secondary outcomes (6)
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.
Measured: 4 weeks
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.
Measured: 16 weeks
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.
Measured: 4 weeks
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.
Measured: 4 weeks
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.
Measured: 8 weeks
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.
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2016 (estimated)
- Study start1 Jun 2017
- Primary completion3 Dec 2018
- Study completion3 Dec 2018
Why it stopped: Due low efficacy of FMT in interim analysis.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PouchitisStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- OpenBiome, Crohn's and Colitis Foundation, The Broad Foundation
- Responsible party
- Sponsor
- Investigators
- Hans Herfarth, MD, PhD, Principal investigator, University of North Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02782325
- Sponsor's protocol ID
- 16-1310
- Other IDs
- FMTADP
- Status last verified
- Dec 2018
- First submitted
- 12 May 2016
- Last updated
- 14 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: The final results of the trial will be posted on clinical trials.gov. No individual patient data will be posted.
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Fecal Microbiome Transplantation (FMT) in the Treatment of Antibiotic Dependent Pouchitis (ADP)
- ClinicalTrials.gov ID
- NCT02782325
- Acronym / sponsor ID
- 16-1310
- Conditions
- Pouchitis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due low efficacy of FMT in interim analysis.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- OpenBiome, Crohn's and Colitis Foundation, The Broad Foundation
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 3 Dec 2018 (actual)
- Study completion
- 3 Dec 2018 (actual)
- First posted
- 25 May 2016 (estimated)
- Results
- Posted 14 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active FMT, then open label FMT | Active comparator | Biological: Active FMT, then open label FMTEndoscopic 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. |
| Placebo FMT, then open label FMT | Placebo comparator | Biological: Placebo FMT, then open label FMTEndoscopic 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active FMT, then open label FMTAlso: Active FMTEndoscopic 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. | Biological | Active FMT, then open label FMT |
| Placebo FMT, then open label FMTAlso: Placebo FMTEndoscopic 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. | Biological | Placebo FMT, then open label FMT |
Primary outcome
Number of Patients With FMT Related Adverse Event
Time frame: 24 weeks
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.
6 secondary outcomes
Number of Patients in Clinical Remission Week 4 After Endoscopic and Oral FMT
Time frame: 4 weeks
Number of Patients in Clinical Remission Week 16
Time frame: 16 weeks
Number of Patients With Endoscopic Improvement Week 4 After Endoscopic and Oral FMT
Time frame: 4 weeks
Number of Patients With Clinical Response at Week 4 in Patients Entering the Trial With Active Pouchitis Symptoms
Time frame: 4 weeks
Number of Patients With Clinical Response Week 8 and Active Pouchitis at Baseline
Time frame: 8 weeks
Number of Patients With Clinical Response i at Week 16 and Active Pouchitis at Baseline
Time frame: 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. The final results of the trial will be posted on clinical trials.gov. No individual patient data will be posted.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hans Herfarth, MD, PhD principal investigator
University of North Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Active FMT, then open label FMT in people with Pouchitis, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With FMT Related Adverse Event (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2019.