Ulcerative Colitis
Conditions
Keywords
Ulcerative colitis, Inflammatory bowel disease, Fecal microbiota transplantation
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.
Interventions
DRUGFecal 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.
DRUGSham-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.
Sponsors
CRB-HUEP
Institut National de la Santé Et de la Recherche Médicale, France
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Steroid-free clinical remission | 12 weeks after FMT or sham-transplantation | Steroid-free clinical remission defined as a Partial Mayo Clinic score of 0 or 1 |
| Inflammatory biological parameter 2 | up to 24 weeks | fecal calprotectin |
| Inflammatory biological parameter 3 | up to 24 weeks | platelet number |
| Endoscopic lesions | 12 weeks after FMT or sham-transplantation | Endoscopic lesions at coloscopy and sigmoidoscopy by endoscopic Mayo score |
| Inflammatory biological parameter 1 | up to 24 weeks | CRP |
Countries
France
Outcome results
None listed