Clinical trial NCT03483246: Impact of Fecal Microbiota Transplantation in Ulcerative Colitis
Official title: Impact of Fecal Microbiota Transplantation in Ulcerative Colitis: a Randomized, Sham Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ulcerative Colitis
Keywords: Ulcerative colitis
Inflammatory bowel disease
Fecal microbiota transplantation
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: CRB-HUEP
name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2018-03-30
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Steroid-free clinical and endoscopic remission
timeFrame: 12 weeks after FMT or sham-transplantation
Secondary outcomes:
measure: Steroid-free clinical remission
timeFrame: 12 weeks after FMT or sham-transplantation
measure: Steroid-free clinical remission
timeFrame: 24 weeks after FMT or sham-transplantation
measure: Steroid-free endoscopic response
timeFrame: 12 weeks after FMTor sham-transplantation
measure: Steroid-free endoscopic remission
timeFrame: 12 weeks after FMT or sham-transplantation
measure: Microbiota composition and diversity
timeFrame: 12 and 24 weeks after FMT or sham-transplantation
measure: Proportion of adverse events in each group
timeFrame: Through study completion, up to 25 months and one week
measure: Inflammatory biological parameter 1
timeFrame: up to 24 weeks
measure: Inflammatory biological parameter 2
timeFrame: up to 24 weeks
measure: Inflammatory biological parameter 3
timeFrame: up to 24 weeks
measure: Endoscopic lesions
timeFrame: 12 weeks after FMT or sham-transplantation
measure: Endoscopic lesions
timeFrame: 12 weeks after FMT or sham-transplantation
Other outcomes:
Locations:
city: Paris
country: France
facility: Service de Gastroentérologie et Nutrition Hôpital Saint Antoine
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Harry SOKOL, PU-PH
role: PRINCIPAL_INVESTIGATOR
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