Impact of Fecal Microbiota Transplantation in Ulcerative Colitis (REBALANCE-UC)

February 28, 2024 updated by: Assistance Publique - Hôpitaux de Paris

Impact of Fecal Microbiota Transplantation in Ulcerative Colitis: a Randomized, Sham Controlled Trial

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. UC pathogenesis remains poorly understood but involves an inappropriate immune response toward an unbalanced gut microbiota (called dysbiosis) in predisposed hosts.

The purpose of this study is to determine the effect of the fecal microbiota transplantation on UC.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease affecting approximately 90 000 patients in France, mostly at young age, and altering their quality of life.

Conventional Immunosuppressive treatment (ie azathioprine, anti-TNF (tumor necrosis factor ), vedolizumab) used in UC are expensive and associated with potentially severe complications such as infections and cancers.

UC pathogenesis remains poorly understood but involves an inappropriate immune response toward an unbalanced gut microbiota (called dysbiosis) in predisposed hosts.

Fecal microbiota transplantation (FMT) is now recommended in guidelines for treating recurrent Clostridium difficile infection. Although the pathogenesis involved in UC is different, FMT is a potential therapeutic strategy as transferring a healthy microbiota in an UC patient could restore the appropriate host-microbiota crosstalk.

As the gut microbiota is dramatically altered by intestinal inflammation, transferring a massive amount of microbial organisms in an inflamed gut with epithelial barrier disruption might be a suboptimal strategy and could even have detrimental effects by allowing bacterial translocation.

Thus, it's possible that performing FMT in UC patients who achieved remission after conventional treatment might be associated with better clinical outcome than in patients with active disease.

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Paris, France, 75012
        • Recruiting
        • Service de Gastroentérologie et Nutrition Hôpital Saint Antoine
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 74 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

Inclusion Criteria for patients :

  • Age ≥ 18 years and < 75 years

  • Ulcerative colitis (according to the Lennard Jones criteria) diagnosed for at least 3 months and :

    • Currently active (PMC > 1) and planned to be treated by systemic corticosteroids (minimum 40mg prednisone equivalent daily) Or
    • Currently treated by systemic corticosteroid (minimum 40 mg prednisone equivalent daily) within max 3 weeks Or
    • Steroid dependent patients (at least one unsuccessful attempt to discontinue steroid within the last 6 months before inclusion)
  • Patient with health insurance (AME excepted)
  • Informed written consent
  • Female of child-bearing age with an active contraception and this during at least period of treatment until the end of active follow-up period (week 24)

Inclusion Criteria for healthy volunteers donors :

  • Age ≥ 18 years and < 50 years
  • 17 kg/m² < body mass index < 30 kg/m²
  • Regular bowel movement defined as at least 1 stool every other day and maximum 2 stools per day
  • Subject with health insurance (AME excepted)
  • Informed Written consent

Exclusion Criteria:

Exclusion Criteria for patients :

  • UC complication requiring surgical treatment
  • Patient treated with high dose corticosteroid more than three weeks before inclusion (≥ 40 mg prednisone equivalent daily) except in case of steroid-dependence
  • Contraindication to colonoscopy or anesthesia
  • Pregnancy or breastfeeding during the study

  • Treatment preceding the colonoscopy with:

    • intravenous infliximab and/or vedolizumab and/or ustekinumab (< 6 weeks before the planned date of the colonoscopy) and/or subcutaneous infliximab (<2 weeks before the planned date of the colonoscopy), and /or adalimumab (<2 weeks before the planned date of the colonoscopy) and/or golimumab and/or tofacitinib (<4 weeks before the planned date of the colonoscopy)
    • immunosuppressant (thiopurine, methotrexate, tacrolimus or other classical immunosuppressant) started or stopped < 3 months before the planned date of the colonoscopy
    • Antibiotics, antifungic or probiotics treatment < 4 weeks before the planned date of the colonoscopy
  • participation in any other interventional study
  • patient under legal protection

Exclusion Criteria for healthy volunteers donors :

- For details, please see protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group B - fecal microbiota transplantation
Patients receiving the fecal microbiota transplantation (FMT) in 3 times after inclusion and randomisation
Drug: Fecal Microbiota Transplantation (FMT)

The colonoscopy for FMT will be planned as soon as possible and never more than 5 weeks after inclusion visit.

After colon cleansing using Polyethylen glycol, the patient will have a colonoscopy under general anesthesia.

The patient will then receive either FMT (frozen preparation of 50g of stools in 300ml of physio, see donor section for details) or sham transplantation (FMT vehicle) in the cecum.
Placebo Comparator: Group A- Sham-transplantation
Patients receiving the sham-transplantation in 3 times after inclusion and randomisation
Drug: Sham-transplantation Placebo

The sham-transplantation will be planned as soon as possible and never more than 5 weeks after inclusion visit.

After colon cleansing using Polyethylen glycol, the patient will have a colonoscopy under general anesthesia.

The patient will then sham transplantation (FMT vehicle) in the cecum.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Steroid-free clinical and endoscopic remission
Time Frame: 12 weeks after FMT or sham-transplantation
Steroid-free clinical and endoscopic remission defined as a total Mayo score of 2 or lower and no subscore higher than 1 and mucosal healing defined as an endoscopic subscore of 0 or 1 (Sigmoidoscopy).
12 weeks after FMT or sham-transplantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Steroid-free clinical remission
Time Frame: 12 weeks after FMT or sham-transplantation
Steroid-free clinical remission defined as a Partial Mayo Clinic score of 0 or 1
12 weeks after FMT or sham-transplantation
Steroid-free clinical remission
Time Frame: 24 weeks after FMT or sham-transplantation
Steroid-free clinical remission defined as a Partial Mayo Clinic score of 0 or 1
24 weeks after FMT or sham-transplantation
Steroid-free endoscopic response
Time Frame: 12 weeks after FMTor sham-transplantation
Steroid-free endoscopic response defined as a Mayo endoscopy subscore of 1 or less, with a reduction of at least 1 point from baseline
12 weeks after FMTor sham-transplantation
Steroid-free endoscopic remission
Time Frame: 12 weeks after FMT or sham-transplantation
Steroid-free endoscopic remission defined as an Endoscopic Mayo Clinic score of 0
12 weeks after FMT or sham-transplantation
Microbiota composition and diversity
Time Frame: 12 and 24 weeks after FMT or sham-transplantation
Microbiota composition and diversity assessed by 16s sequencing compared to baseline and to donor's microbiota.
12 and 24 weeks after FMT or sham-transplantation
Proportion of adverse events in each group
Time Frame: Through study completion, up to 25 months and one week
abdominal pain, nausea, vomiting, fever, modified intestinal transit and episode of infection
Through study completion, up to 25 months and one week
Inflammatory biological parameter 1
Time Frame: up to 24 weeks
CRP
up to 24 weeks
Inflammatory biological parameter 2
Time Frame: up to 24 weeks
fecal calprotectin
up to 24 weeks
Inflammatory biological parameter 3
Time Frame: up to 24 weeks
platelet number
up to 24 weeks
Endoscopic lesions
Time Frame: 12 weeks after FMT or sham-transplantation
Endoscopic lesions at coloscopy and sigmoidoscopy by endoscopic Mayo score
12 weeks after FMT or sham-transplantation
Endoscopic lesions
Time Frame: 12 weeks after FMT or sham-transplantation
Endoscopic lesions at coloscopy (baseline) and sigmoidoscopy by UCEIS score
12 weeks after FMT or sham-transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France
CRB-HUEP

Investigators

  • Principal Investigator: Harry SOKOL, PU-PH, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 17, 2018

Primary Completion (Estimated)

November 17, 2024

Study Completion (Estimated)

December 24, 2026

Study Registration Dates

First Submitted

February 26, 2018

First Submitted That Met QC Criteria

March 23, 2018

First Posted (Actual)

March 30, 2018

Study Record Updates

Last Update Posted (Estimated)

February 29, 2024

Last Update Submitted That Met QC Criteria

February 28, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P 160931J
  • 2017-003802-42 (EudraCT Number)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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