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

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ClinicalTrials.gov Identifier: NCT03483246
Recruitment Status : Not yet recruiting
First Posted : March 30, 2018
Last Update Posted : August 13, 2018
Sponsor:
Collaborators:
CRB-HUEP
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: Fecal Microbiota Transplantation (FMT) Drug: Sham-transplantation Placebo Phase 3

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  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Impact of Fecal Microbiota Transplantation in Ulcerative Colitis: a Randomized, Sham Controlled Trial
Estimated Study Start Date : September 2018
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group A - 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 4 liters of 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 B- 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 4 liters of Polyethylen glycol, the patient will have a colonoscopy under general anesthesia.

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





Primary Outcome Measures :
  1. Steroid-free clinical and endoscopic remission [ Time Frame: 12 weeks after FMT or sham-transplantation ]
    Steroid-free clinical and endoscopic remission defined as a Mayo Clinic 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 :
  1. 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

  2. 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

  3. 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

  4. 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 or 1

  5. 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.

  6. Proportion of adverse events in each group [ Time Frame: Through study completion, an evrage of 4 years ]
    abdominal pain, nausea, vomiting, fever, modified intestinal transit

  7. Inflammatory biological parameter 1 [ Time Frame: up to 24 weeks ]
    CRP

  8. Inflammatory biological parameter 2 [ Time Frame: up to 24 weeks ]
    fecal calprotectin

  9. Inflammatory biological parameter 3 [ Time Frame: up to 24 weeks ]
    platelet number

  10. Endoscopic lesions [ Time Frame: 12 weeks after FMT or sham-transplantation ]
    Endoscopic lesions at coloscopy (baseline) and sigmoidoscopy by endoscopic Mayo score

  11. Endoscopic lesions [ Time Frame: 12 weeks after FMT or sham-transplantation ]
    Endoscopic lesions at coloscopy (baseline) and sigmoidoscopy by UCEIS score



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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 12 weeks before inclusion)
  • Patient with health insurance (AME excepted)
  • Informed written consent

Inclusion Criteria for donors :

  • Age ≥ 18 years and < 50 years
  • 17 kg/m² < body mass index < 30 kg/m²
  • Regular bowel movement in the morning
  • 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
  • Treatment preceding the colonoscopy with:

    • infliximab and/or vedolizumab (< 6 weeks before the planned date of the colonoscopy) and/or adalimumab (<2 weeks before the planned date of the colonoscopy) and/or golimumab (<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

Exclusion Criteria for donors :

- For details, please see protocol.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03483246


Contacts
Contact: Harry SOKOL, PU-PH 01 49 28 31 62 harry.sokol@aphp.fr
Contact: Laurent BEAUGERIE, PU-PH 01 49 28 31 62 laurent.beaugerie@aphp.fr

Locations
France
Service de Gastroentérologie et Nutrition Hôpital Saint Antoine Not yet recruiting
Paris, France, 75012
Contact: Harry SOKOL, PU-PH    01 49 28 31 62    harry.sokol@aphp.fr   
Contact: Laurent Beaugerie, PU-PH    01 49 28 31 62    laurent.beaugerie@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
CRB-HUEP
Institut National de la Santé Et de la Recherche Médicale, France
Investigators
Principal Investigator: Harry SOKOL, PU-PH Assistance Publique - Hôpitaux de Paris

Publications:

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03483246     History of Changes
Other Study ID Numbers: P 160931J
2017-003802-42 ( EudraCT Number )
First Posted: March 30, 2018    Key Record Dates
Last Update Posted: August 13, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Ulcerative colitis
Inflammatory bowel disease
Fecal microbiota transplantation

Additional relevant MeSH terms:
Colitis
Ulcer
Colitis, Ulcerative
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases