Screening Donors, Fecal Microbiota Transplant Program in Ulcerative Colitis (FUEL)

Screening Donors for a Fecal Microbiota Transplant Program in Ulcerative Colitis: Evaluating Efficacy and Long-term Effects. The FUEL Study

The investigators intend to screen for new donors, given that there may a donor effect (PubMed ID: 25857665), with some donors not inducing remission in any patient whilst others inducing remission in 20-40% of cases. It is important to give UC patients participating in RCTs stool that has been demonstrated to be effective in some patients. We therefore propose to conduct an open label study in patients with active UC to ensure new donors are effective at inducing remission in some patients. Patients that have FMT will relapse within 18 months (PubMed ID: 25857665) although further FMT therapy induces remission so it is possible that maintenance FMT will result in long term remission, but this needs evaluation. We will therefore follow UC patients that have responded to FMT long term in this open label study.

Study Overview

• Status: Not yet recruiting
• Conditions: Ulcerative Colitis Flare
• Intervention / Treatment: Other: Fecal Microbiota transplant (FMT)

Detailed Description

This is an open label study with all UC patients receiving FMT. Up to 200 patients with active UC will be recruited to the study.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Melanie A Wolfe, CCRP; Phone Number: 22060 9055212100; Email: wolfe@hhsc.ca
• Study Contact Backup: Name: Aida Fernandes, MBA; Phone Number: 289-921-6483; Email: fernaa19@mcmaster.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Hamilton Health Sciences / McMaster University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients aged 18 or over
2. Active UC defined as a Mayo score (7) >3
3. A Mayo endoscopic score (7) >0
4. 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 intervention study for UC
2. Unable to give informed consent
3. Severe comorbid medical illness
4. Severe UC requiring hospitalization.
5. Increase in medical therapy for UC in the last 12 weeks. Continued treatment with 5-ASA, azathioprine, 6-mercaptopurine or anti-TNF therapy (e.g. infliximab) will be permitted if taken at stable dose for ≥12 weeks prior to randomization. Relapse on a 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. Antibiotic therapy in the last 30 days.
7. Pregnant women.
8. Patients with clinically significant hepatic dysfunction at the time of screening: ALT > 5 times the upper normal range.
9. Patients with clinically significant renal dysfunction at the time of screening: serum creatinine > 300 µmol/L
10. Any condition, in the opinion of the investigator, that the treatment may pose a health risk to the subject.

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: Open label FMT therapy; FMT from a related or unrelated healthy donor screened for known communicable disease

Other: Fecal Microbiota transplant (FMT); Patients will come once a week for FMT for 8 weeks. FMT is the administration of the supernatant component of stool and water mixture from a healthy relative or an unrelated donor. The donor's stool and blood is rigorously screened to exclude known communicable diseases. Those that achieve remission with FMT will have the option of continuing FMT once per month for 3 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of FMT donors at inducing UC remission	Suitability of FMT donors at inducing remission in active UC (remission defined as a Mayo score (7) < 3 with an endoscopic Mayo score = 0 at the end of 8 weeks of FMT).	9 weeks
Efficacy of FMT at maintaining remission in UC	Maintenance of remission of UC after three years in those who achieve initial remission with FMT. This is defined as no relapse over three years that requires any medical therapy other than more intense FMT therapy	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of FMT at in inducing histological remission in active UC	Histological remission with no active inflammation on rectal and sigmoid biopsies	9 weeks
Efficacy of FMT at relieving PRO2 symptoms	A score of zero on the first two questions of the Mayo Score	9 weeks
Efficacy of FMT at improving Quality of life	Improvement in quality of life from baseline measured by EQ5D	9 weeks and 3 years
Adverse effects of FMT	Adverse effects associated with FMT therapy	3 years
Stool microbiota predicting FMT success	Comparison of stool microbiota evaluated by 16s RNA and metagenomics in those achieving remission with FMT versus those that are not successful	9 weeks
Mucosal microbiota predicting FMT success	Comparison of mucosal microbiota evaluated by 16s RNA and metagenomics in those achieving remission with FMT versus those that are not successful	9 weeks

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Paul Moayyedi, MD, HHSC/McMaster

Publications and helpful links

General Publications

• Moayyedi P, Surette MG, Kim PT, Libertucci J, Wolfe M, Onischi C, Armstrong D, Marshall JK, Kassam Z, Reinisch W, Lee CH. Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology. 2015 Jul;149(1):102-109.e6. doi: 10.1053/j.gastro.2015.04.001. Epub 2015 Apr 7.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2022
• Primary Completion (Anticipated): October 1, 2028
• Study Completion (Anticipated): May 1, 2029

Study Registration Dates

• First Submitted: May 12, 2021
• First Submitted That Met QC Criteria: June 10, 2021
• First Posted (Actual): June 14, 2021

Study Record Updates

• Last Update Posted (Actual): March 16, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

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: FUEL001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Approach investigator to ask for anonymized dataset
• IPD Sharing Time Frame: Data will be available after study completion - estimated 7 years
• IPD Sharing Access Criteria: Any researcher evaluating the efficacy of FMT in ulcerative colitis
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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