Impact of Fecal Microbiota Transplantation in Ulcerative Colitis
- Conditions
- Ulcerative Colitis
- Interventions
- Drug: Fecal Microbiota Transplantation (FMT)Drug: Sham-transplantation Placebo
- Registration Number
- NCT03483246
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 150
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 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group B - fecal microbiota transplantation Fecal Microbiota Transplantation (FMT) Patients receiving the fecal microbiota transplantation (FMT) in 3 times after inclusion and randomisation Group A- Sham-transplantation Sham-transplantation Placebo Patients receiving the sham-transplantation in 3 times after inclusion and randomisation
- Primary Outcome Measures
Name Time Method Steroid-free clinical and endoscopic remission 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).
- Secondary Outcome Measures
Name Time Method Endoscopic lesions 12 weeks after FMT or sham-transplantation Endoscopic lesions at coloscopy (baseline) and sigmoidoscopy by UCEIS score
Inflammatory biological parameter 3 up to 24 weeks platelet number
Steroid-free clinical remission 24 weeks after FMT or sham-transplantation Steroid-free clinical remission defined as a Partial Mayo Clinic score of 0 or 1
Steroid-free endoscopic response 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
Steroid-free endoscopic remission 12 weeks after FMT or sham-transplantation Steroid-free endoscopic remission defined as an Endoscopic Mayo Clinic score of 0
Microbiota composition and diversity 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.
Proportion of adverse events in each group Through study completion, up to 25 months and one week abdominal pain, nausea, vomiting, fever, modified intestinal transit and episode of infection
Inflammatory biological parameter 1 up to 24 weeks CRP
Inflammatory biological parameter 2 up to 24 weeks fecal calprotectin
Trial Locations
- Locations (1)
Service de Gastroentérologie et Nutrition Hôpital Saint Antoine
🇫🇷Paris, France