Impact of Fecal Microbiota Transplantation in Ulcerative Colitis

Ulcerative Colitis Clinical Trial

— REBALANCE-UC  

Official title:

Impact of Fecal Microbiota Transplantation in Ulcerative Colitis: a Randomized, Sham Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03483246
• Other study ID #: P 160931J
• Secondary ID: 2017-003802-42
• Status: Recruiting
• Phase: Phase 3
• Start date: September 17, 2018
• Est. completion date: December 24, 2026

Study information

• Verified date: February 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Harry SOKOL, PU-PH
• Phone: 01 49 28 31 62
• Email: harry.sokol[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 24, 2026
• Est. primary completion date: November 17, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

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 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.
• 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 Polyethylen glycol, the patient will have a colonoscopy under general anesthesia. The patient will then sham transplantation (FMT vehicle) in the cecum.

Locations

Country	Name	City	State
France	Service de Gastroentérologie et Nutrition Hôpital Saint Antoine	Paris

Sponsors (3)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	CRB-HUEP, Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

References & Publications (28)

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* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Steroid-free clinical and endoscopic remission	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).	12 weeks after FMT or sham-transplantation
Secondary	Steroid-free clinical remission	Steroid-free clinical remission defined as a Partial Mayo Clinic score of 0 or 1	12 weeks after FMT or sham-transplantation
Secondary	Steroid-free clinical remission	Steroid-free clinical remission defined as a Partial Mayo Clinic score of 0 or 1	24 weeks after FMT or sham-transplantation
Secondary	Steroid-free endoscopic response	Steroid-free endoscopic response defined as a Mayo endoscopy subscore of 1 or less, with a reduction of at least 1 point from baseline	12 weeks after FMTor sham-transplantation
Secondary	Steroid-free endoscopic remission	Steroid-free endoscopic remission defined as an Endoscopic Mayo Clinic score of 0	12 weeks after FMT or sham-transplantation
Secondary	Microbiota composition and diversity	Microbiota composition and diversity assessed by 16s sequencing compared to baseline and to donor's microbiota.	12 and 24 weeks after FMT or sham-transplantation
Secondary	Proportion of adverse events in each group	abdominal pain, nausea, vomiting, fever, modified intestinal transit and episode of infection	Through study completion, up to 25 months and one week
Secondary	Inflammatory biological parameter 1	CRP	up to 24 weeks
Secondary	Inflammatory biological parameter 2	fecal calprotectin	up to 24 weeks
Secondary	Inflammatory biological parameter 3	platelet number	up to 24 weeks
Secondary	Endoscopic lesions	Endoscopic lesions at coloscopy and sigmoidoscopy by endoscopic Mayo score	12 weeks after FMT or sham-transplantation
Secondary	Endoscopic lesions	Endoscopic lesions at coloscopy (baseline) and sigmoidoscopy by UCEIS score	12 weeks after FMT or sham-transplantation