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

Assistance Publique - Hôpitaux de Paris

Status and phase: Active, not recruiting; Phase 3

Conditions: Ulcerative Colitis

Treatments: Drug: Sham-transplantation Placebo; Drug: Fecal Microbiota Transplantation (FMT)

Study type: Interventional

Funder types: Other

Identifiers

NCT03483246

P 160931J

2017-003802-42 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 150 estimated patients

Sex: All

Ages: 18 to 74 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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150 participants in 2 patient groups, including a placebo group

Group B - fecal microbiota transplantation

Experimental group

Description:

Patients receiving the fecal microbiota transplantation (FMT) in 3 times after inclusion and randomisation

Treatment:

Drug: Fecal Microbiota Transplantation (FMT)

Group A- Sham-transplantation

Placebo Comparator group

Description:

Patients receiving the sham-transplantation in 3 times after inclusion and randomisation

Treatment:

Drug: Sham-transplantation Placebo