FMT for Remission of Active Ulcerative Colitis in Adults

• ClinicalTrials.gov Identifier: NCT04202211
• Recruitment Status: Not yet recruiting
• First Posted: December 17, 2019
• Last Update Posted: December 18, 2019
• Sponsor: University of British Columbia
• Collaborators: Crohn's and Colitis Canada; Vancouver Island Health Authority
• Information provided by (Responsible Party): Theodore Steiner, University of British Columbia

Study Description

Brief Summary:

The goal of this study is to establish the safety and effectiveness of lyophilized (LYO) fecal microbiota transplant (FMT) for treating ulcerative colitis (UC) in adults. This is multi-site, randomized double-blind, placebo-controlled trial. UC patients with active disease will be recruited at three Canadian centres and the study involves 3 treatment arms:

1. FMT oral capsules + placebo enema
2. placebo oral capsules + placebo enema
3. FMT oral capsules and FMT enema The primary outcome is achievement of remission of UC; the efficacy of LYO-FMT in achieving remission of active ulcerative colitis in adults will be evaluated.

Condition or disease	Intervention/treatment	Phase
Ulcerative Colitis; Inflammatory Bowel Diseases	Biological: FMT oral; Biological: FMT enema; Other: Placebo oral; Other: Placebo enema	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 145 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 145 active UC participants will be randomized to one of the three treatment groups in 1:2:2 randomization ratio
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Gastroenterologists performing flexible sigmoidoscopes will remain blinded to participant's treatment. One unblinded nurse will administer the FMT enema.
• Primary Purpose: Treatment
• Official Title: A Randomized Double-blind, Placebo-controlled Trial of Lyophilized Fecal Microbiota Transplantation for the Induction of Remission in Adults With Active Ulcerative Colitis
• Estimated Study Start Date: February 2020
• Estimated Primary Completion Date: May 2023
• Estimated Study Completion Date: February 2025

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo oral & enema; twice weekly x 8 weeks: 10 placebo oral capsules + placebo enema	Other: Placebo oral; placebo given orally (10 capsules) twice weekly for total of 8 weeks; Other: Placebo enema; placebo given via enema (1) twice weekly for total of 8 weeks
Active Comparator: LYO-FMT oral + placebo enema; twice weekly x 8 weeks: 10 LYO-FMT oral capsules + 1 placebo enema	Biological: FMT oral; lyophilized FMT given orally (10 capsules) twice weekly for total of 8 weeks; Other: Placebo enema; placebo given via enema (1) twice weekly for total of 8 weeks
Active Comparator: LYO-FMT oral + LYO-FMT enema; twice weekly x 8 weeks: 10 LYO-FMT oral capsules + 1 LYO-FMT enema	Biological: FMT oral; lyophilized FMT given orally (10 capsules) twice weekly for total of 8 weeks; Biological: FMT enema; lyophilized FMT given via enema (1) twice weekly for total of 8 weeks

Outcome Measures

Primary Outcome Measures :

1. Remission of UC [ Time Frame: 9 weeks following receipt of LYO-FMT ]
   achievement of remission of UC as defined by Mayo score ≤ 2 AND Mayo endoscopic score of ≤ 1

Secondary Outcome Measures :

1. Incidence/absence of adverse events upon treatment with LYO-FMT [safety and tolerability] [ Time Frame: up to 5 years post-FMT ]
   Safety of LYO-FMT in patients with active UC as determined by absence of adverse events
2. UC disease progression [ Time Frame: immediately after FMT (study) treatment period up to 5 years post-FMT ]

   Determine progression of UC based on development of any of the following:

   1. Clinical flare of UC requiring hospitalization up to 3 months post-FMT
   2. Increase in dosages of current UC specific medications up to 3 months' post FMT
   3. Time to colectomy for UC flare up to 12 months' post FMT
   4. Time to death directly attributable to UC up to 5 years post FMT
   5. Improvement in clinical response defined by decrease in Partial Mayo score by ≥ 3 points from pre to post LYO-FMT.
   6. Improvement in patient-reported health related QoL using Valuation of Lost Productivity and (VOLP) and RAND VR12 measured at pre and at 5 weeks, 12 and 24 weeks following LYO-FMT and annually for 5 years
   7. Reduction in biologic inflammatory markers (serum c-reactive protein (CRP) and fecal calprotectin) from pre to post LYO-FMT

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Able to provide informed consent.
• Willing and able to comply with all the required trial procedures
• Active ulcerative colitis as defined by Mayo score > 3 AND Mayo endoscopic sub-score > 1 (within 30 days before enrollment, or at baseline)

Exclusion Criteria:

• Planned or actively taking another investigational product
• Abdominal surgery within the past 60 days
• Patients with neutropenia with absolute neutrophil count <0.5 x 109/L at - Evidence of toxic megacolon or gastrointestinal perforation on imaging
• Peripheral white blood cell count > 35.0 x 109/L at enrollment AND temperature > 38.0oC
• Active infectious diarrhea at the time of enrolment
• Increase in medical therapy for UC within 3 months of enrollment. Continued treatment with stable dose of 5-ASA, azathioprine, 6-mercaptopurine, cyclosporine, prednisone and/or anti- TNF agents for at least 3 months of is allowed
• Severe UC requiring hospitalization at the time of enrolment
• Pregnant or lactating
• History of anaphylaxis to any food
• Requiring oral and/or intravenous systemic antibiotic therapy at the time of study enrolment
• Unwilling to discontinue probiotic (yogurt is allowed)
• Severe underlying disease such that the patient is not expected to survive for at least 30 days.
• Any condition that in the opinion of the investigator that would pose harm to the participant or the research staff for the potential participant to take part in the trial

Contacts and Locations

Contacts

Contact: Laura Oliveira; 604 875 4111 ext 64164; laura.oliveira@ubc.ca

Locations

Canada, Alberta

University of Alberta Hospital

Edmonton, Alberta, Canada, T6G 2B7

Contact: Rose Franz Rose.Franz@albertahealthservices.ca

Principal Investigator: Dina Kao, MD

Canada, British Columbia

Vancouver General Hospital

Vancouver, British Columbia, Canada, V5Z 1M9

Contact: Laura Oliveira 604 875 4111 ext 64164 laura.oliveira@ubc.ca

Principal Investigator: Ted Steiner, MD

Royal Jubilee Hospital

Victoria, British Columbia, Canada, V8R 1J8

Contact: Peyman Goldeh Peyman.Goldeh@VIHA.CA

Principal Investigator: Christine Lee, MD

Sponsors and Collaborators

University of British Columbia

Crohn's and Colitis Canada

Vancouver Island Health Authority

Investigators

• Principal Investigator: Ted Steiner, MD; University of British Columbia

More Information

• Responsible Party: Theodore Steiner, MD, Professor, University of British Columbia
• ClinicalTrials.gov Identifier: NCT04202211
• Other Study ID Numbers: H19-03882
• First Posted: December 17, 2019
• Last Update Posted: December 18, 2019
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Theodore Steiner, University of British Columbia:

ulcerative colitis; Fecal Microbiota transplant; FMT; Inflammatory bowel disease; IBD

Additional relevant MeSH terms:

Colitis; Colitis, Ulcerative; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Pathologic Processes