Transfer of Feces in Ulcerative Colitis 2 (TURN2)

Transfer of Feces in Ulcerative Colitis 2; Improving Efficacy

The goal of this placebo-controlled randomised multicenter trial is to evaluate the efficacy and safety of anaerobic prepared donor fecal microbiota transplantation (FMT) compared to autologous FMT in patient with ulcerative colitis.

Participants will receive 4 treatments with frozen FMT via both upper and lower gastro-intestinal route (infusion via duodenal tube and enemas).

Donors are selected based on microbiota profile.

Study Overview

• Status: Recruiting
• Conditions: Ulcerative Colitis; Ulcerative Colitis Flare; Ulcerative Colitis Acute
• Intervention / Treatment: Other: Fecal microbiota transplant

• Study Type: Interventional
• Enrollment (Estimated): 76
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Cyriel Ponsioen, prof.; Phone Number: +31 20 5668278; Email: c.y.ponsioen@amsterdamumc.nl
• Study Contact Backup: Name: Melanie Benard, Msc; Phone Number: 0031645050314; Email: m.v.benard@amsterdamumc.nl

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1061BK
      • Recruiting
      • Amsterdam University Medical Center
      • Contact: Melanie V. Bénard, Msc; Email: m.v.benard@amsterdamumc.nl
      • Contact: Florine Jiwa; Email: f.h.jiwa@amsterdamumc.nl
      • Principal Investigator: Rinse K. Weersma, Prof. dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age ≥18 and <70
• Ability to give informed consent
• Established ulcerative colitis with known involvement of the left colon according to the Lennard-Jones criteria
• Partial mayo score of ≥ 3 and calprotectin > 250
• Full Mayo score 5-9
• Endoscopic Mayo score of ≥2 in either the rectum or sigmoid upon screening sigmoidoscopy
• Stable dose of thiopurines or , 5-ASA, or budesonide in preceding 8 weeks.
• Stable dose of budesonide in preceding 2 weeks.
• Prednisone use ≤15mg/day in preceding 2 weeks with a mandatory taper of 5 mg per week starting from week 4.
• Women need to use reliable contraceptives during participation in the study
• Alkaline phosphatase > 1.5 x ULN in the subgroup of PSC/UC patients.

Exclusion Criteria:

• Condition leading to profound immunosuppression

  • For example: HIV, infectious diseases leading to immunosuppression, bone marrow malignancies
  • Use of systemic chemotherapy
  • Child-Pugh B liver cirrhosis
• Anti-TNFα treatment in preceding 2 months
• Vedolizumab treatment in preceding 2 months
• Tofacitinib treatment in preceding 2 months
• Ustekinumab treatment in preceding 2 months
• Cyclosporine treatment in preceding 4 weeks
• Use of Methotrexate in preceding 2 months
• Prednisolone dose > 15 mg/day in preceding 2 weeks
• Use of topical therapy in preceding 2 weeks
• Life expectancy < 12 months
• Difficulty with swallowing
• Use of systemic antibiotics in preceding 4 weeks
• Use of probiotic treatment in preceding 4 weeks
• Positive stool cultures for common enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, enteropathogenic e coli)
• Positive C. Difficile stool test
• Positive dual faeces test for pathogenic parasites e.g. Dientamoeba histolytica, Giardia Lamblia, Dientamoeba fragilis, Blastocystis hominis only if microscopically many or very many blastocysts are seen.
• Positive serological test for HIV

• History of surgery:

  • presence of a pouch
  • presence of stoma
• Known intra-abdominal fistula
• Pregnancy or women who give breastfeeding
• Vasopressive medication, icu stay
• Signs of ileus, diminished passage
• Allergy to macrogol or substituents, eg peanuts, shellfish
• Known allergy to iv gadolinium in the subgroup of patients who would be scheduled for MRI liver
• Crohn's disease
• Subject who has any conditions that in the opinion of the investigator, would compromise the safety of the subject or the quality of the data and is an unsuitable candidate for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Donor fecal microbiota transplant	Other: Fecal microbiota transplant; Frozen FMT via duodenal tube (2 times) and enemas (4 times); Other Names: FMT
Placebo Comparator: Autologous fecal microbiota transplant	Other: Fecal microbiota transplant; Frozen FMT via duodenal tube (2 times) and enemas (4 times); Other Names: FMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical and endoscopic remission	per adapted Mayo: stool frequency subscores (SFS) ≤ 1, rectal bleeding subscore (RBS) =0 and endoscopic subscore ≤ 1. The adapted Mayo score has a minimum score of 0 and a maximum score of 9. The 3 subscores (SFS, RBS, and endoscopic subscore) have a minimum of 0 and a maximum score of 3. The adapted Mayo score does not include PGA (physician global assessment), in contrary to the full Mayo score. A higher score reflects worse outcome.	week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	Adapted Mayo: decrease from baseline ≥ 2 points and ≥ 30% plus a decrease in RBS ≥ 1 or an absolute RBS ≤ 1. The adapted Mayo score has a minimum score of 0 and a maximum score of 9. The 3 subscores (SFS, RBS, and endoscopic subscore) have a minimum of 0 and a maximum score of 3. The adapted Mayo score does not include PGA (physician global assessment), in contrary to the full Mayo score.	week 8
Endoscopic response, evaluated by sigmoidoscopy	•Proportion of patients with ≥1 point reduction in summed endoscopic Mayo score of both the rectum and sigmoid.	week 8

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: University Medical Center Groningen; UMC Utrecht

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2018
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: July 12, 2023
• First Submitted That Met QC Criteria: August 16, 2023
• First Posted (Actual): August 18, 2023

Study Record Updates

• Last Update Posted (Actual): August 18, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 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: NL65069.018.18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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