Combination Therapy With Fecal Microbiota Transplantation and Vedolizumab for Induction of Ulcerative Colitis

This is a pilot study of combination therapy using FMT and vedolizumab for induction of UC. The investigators hypothesize that a combination therapy approach which addresses immune trafficking and microbial manipulation simultaneously will lead to superior outcomes than those seen with single agent therapy.

Study Overview

• Status: Recruiting
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Biological: Fecal microbiota transplantation

Detailed Description

This is a prospective pilot trial involving a single centre (McMaster University Medical Centre) recruiting patients from Hamilton, Ontario Canada and the surrounding regions, to evaluate efficacy and safety outcomes when using fecal microbiota transplantation once weekly for six weeks in UC patients who are initiated on vedolizumab.

A lead in study will be conducted with the first five patients to ensure engraftment of FMT within the colon. Interim analysis will be conducted after these five patients to ensure engraftment within the colon. Data Safety and Monitoring Board will also be informed of the results after the first five patients, including any adverse events. Decision will be made based on these results whether to proceed with the prospective study using FMT weekly for six weeks, or whether to modify the dose/frequency of FMT treatment.

As patients with previous biologic failure tend to have sub-optimal response to vedolizumab monotherapy, this pilot study will focus on recruitment of previous biologic failure patients.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Peter Habashi, RN; Phone Number: 73884 905-521-2100; Email: habashp@hhsc.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S4K1
      • Recruiting
      • Hamilton Health Sciences
      • Contact: Carla Rayan; Email: rayanc@mcmaster.ca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients aged 18 or over
2. Active UC defined as total Mayo score of 6 or more points, with endoscopic subscore at > 2
3. Clinician initiating vedolizumab for patients as per standard of care for UC
4. Patient previously has been exposed to one or more biologic or advanced therapies (anti-TNF, JAK inhibitor, anti-interleukin) and never previously exposed to vedolizumab or other anti-integrin therapy.
5. Females of child bearing potential must be willing and able to use acceptable contraception as per Appendix III. II. b. Toxicity section of the Health Canada Guidance

Exclusion Criteria:

1. Participating in another clinical trial
2. Unable to give informed consent
3. Severe comorbid medical illness
4. Concomitant Clostridium difficile infection
5. Increase in medical therapy for UC in the last 4 weeks. Continued treatment with 5-ASA, azathioprine, or 6-mercaptopurine will be permitted if taken at stable dose for ≥4 weeks prior to study entry. Stable dose (same dose for at least 2 weeks) or a tapering dose of steroids will also be permitted provided the dose of steroid is not increased again. Stable intake of probiotic therapy also permitted.
6. New antibiotic therapy in the last 28 days.
7. Dose of infliximab or golimumab in prior four weeks, adalimumab in prior two weeks, or tofacitinib in prior one week.
8. Pregnant women.
9. Clinically significant lactose intolerance
10. Any condition, in the opinion of the investigator, that the treatment may pose a health risk to the subject, based on lab study results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FMT and vedolizumab; People who are initiating vedolizumab per standard of care for ulcerative colitis will also be offered FMT weekly for 6 weeks.	Biological: Fecal microbiota transplantation; Use of fecal microbiota transplantation enemas once weekly in patients who are initiating vedolizumab treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical remission	The primary outcome of this pilot trial is rate of remission of UC, defined as a total Mayo score of 2 or less, with no subscore greater than 1, and endoscopic healing with a endoscopic subscore of 0 or 1.	Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compliance	Evaluate the number of patients who complete all their FMT and vedolizumab induction visits	Week 6
Clinical response	Evaluation of fecal microbiota transplant and vedolizumab for rate of clinical response (defined as reduction of Mayo score of 2 or more points) at the end of the trial.	Week 6
Endoscopic improvement	Evaluation of fecal microbiota transplant and vedolizumab at rate of endoscopic improvement (defined as reduction of endoscopic Mayo score of 1 or more) at the end of the trial.	Week 6
Fecal microbiome	Compare the fecal microbiome in UC patients in remission versus still active at the end of the trial.	Week 6
Mucosal microbiome	Compare the mucosal microbiome in UC patients in remission versus still active at the end of the trial.	Week 6
Adverse events	Qualitative evaluation of adverse events in patients receiving fecal microbiota transplant and vedolizumab	Week 6

Collaborators and Investigators

• Sponsor: McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: January 2, 2020
• First Submitted That Met QC Criteria: January 13, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: 1001 (Registro Nacional Estudios Clinicos (RNEC))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No