Impact of the Fecal Flora Transplantation on Crohn's Disease

NCT ID: NCT02097797

Last Updated: 2018-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2017-08-30

Brief Summary

Crohn's disease is a chronic and relapsing inflammatory bowel disease. Many data show that the intestinal flora is involved in the disease and it has been show that patients with Crohn's disease exhibit an abnormal fecal flora that might play a role in inflammation. The purpose of this study is to determine the effect of the fecal flora transplantation on Crohn's disease.

Detailed Description

Introduction : Crohn's disease (CD) is an relapsing inflammatory bowel disease relatively frequent. Its prevalence is about 1 for 700 in France, affecting predominantly young adults. Its treatment is based on immunosuppressants that might be associated with potentially severe complications such as infection and cancers. Moreover, these treatments are expensive. The gut microbiota being involved in the disease pathogenesis, it can be considered as a potential therapeutic target.

CD pathogenesis remains poorly understood but involves an inappropriate immune response toward an unbalanced gut microbiota (called dysbiosis) in predisposed hosts. The complete replacement of a dysbiotic microbiota by a "healthy" one is thus an attractive strategy. Fecal transplantation (FT) has been used with success for a long time in the context of Clostridium difficile.

Hypothesis : Fecal transplantation allow the replacement of a dysbiotic microbiota by a " healthy " one with favorable impact on CD evolution.

Primary endpoint : In CD patient with colonic or ileo-colonic involvement put in remission with corticosteroids, Evaluate if FT can modify a dysbiotic fecal microbiota to be closer of the one of a healthy donor.

Methodology

For the Receiver :

Once corticoid-induced remission will be achieved, the patient will be included and randomised to receive either FT or sham transplantation during a colonoscopy. The patient will be evaluated at week 2, 6, 10, 14, 18 and 24. At week 6, a colonoscopy will be performed.

For the Donor :

Donors will be recruited by poster advertising. When a receiver will be included, 3 donors will be contacted to attend an inclusion visit including physical examination as well as blood and stool screening for pathogen. The 3 donors will then come the day of the FT to donate their stool.

Conditions

Crohn's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Fecal Transplantation

patients receiving the fecal transplant (fecal microbiota from a healthy donor)

Group Type: EXPERIMENTAL

Fecal Transplantation

Intervention Type: OTHER

Fecal microbiota (50-100g of stool from donor resuspended in 250-350ml of physiological serum and filtered) given by infusion in coecum during colonoscopy

Sham Transplantation

patients receiving the vehicle (Physiological serum)

Group Type: SHAM_COMPARATOR

Sham Transplantation

Intervention Type: OTHER

250-350ml of physiological serum given by infusion in coecum during colonoscopy

Interventions

Fecal Transplantation

Fecal microbiota (50-100g of stool from donor resuspended in 250-350ml of physiological serum and filtered) given by infusion in coecum during colonoscopy

Intervention Type: OTHER

Sham Transplantation

250-350ml of physiological serum given by infusion in coecum during colonoscopy

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age > 18 years and < 70 years
• Crohn's disease with colonic or ileo-colonic involvement
• Active disease at screening defined by a Harvey Bradshaw Index >4
• Clinical remission (Harvey Bradshaw Index <5) in the 3 weeks following corticosteroid onset
• Patient with health insurance
• Written consent obtained

• Age > 20 years and < 50 years
• 27kg/m² > BMI > 17 kg/m²
• Regular bowel movement with usually one bowel movement in the morning
• Subject with health insurance
• Written consent obtained

Exclusion Criteria

• Fistulizing disease
• Anoperineal or abdominal abscess
• Complication requiring surgical treatment
• Treatment with anti-TNFa (ongoing or stopped in the 1 month preceding randomization)
• Immunosuppressant treatment started or stopped in the 3 months preceding randomization
• Non-steroidal anti inflammatory drugs (NSAIDs) intake in the 4 weeks preceding randomization
• Antibiotics or antifungic treatment in the 4 weeks preceding colonoscopy
• Probiotics intake in the 4 weeks preceding colonoscopy
• Clostridium difficile infection in the 10 days preceding randomization
• contraindication to colonoscopy or anesthesia
• Pregnancy

Donor

• Infection risk:

• Known infection by human immunodeficiency virus (HIV), Human T Leukemia Virus (HTLV), Hepatitis B or C virus.
• At risk behavior: Travel (in the preceding 3 months, excepting in Euro area, United Kingdom, Bulgaria, Poland, Romania, Croatia, Hungary, Republic Tcheque, Denmark, Norway, Sweden, Swiss, USA or Canada), at risk sexual activity (intercourse without protection with a new partner) in the preceding 6 months, blood transfusion, piercing or tattoo in the preceding 6 months residence of several years in intertropical area, abroad hospitalization more than 24 hours in the last 12 months (including patient and his immediate family).
• Positive result at one of the screening tests for infectious disease. : HIV, HCV, HBV, HTLV, syphilis, Enteric viruses (Rotavirus, HEV, Adenovirus, Norovirus, Enterovirus, HAV, Poliovirus, Astrovirus, Aichi virus, Sapovirus), parasites in stool (Cyclospora, Isospora, Cryptosporidium, Microsporidium, Strongyloides stercoralis, Entamoeba histolitica, Giardia intestinalis, Dientamoeba fragilis), and in blood (Strongyloides stercoralis, Trichinella spiralis, Amoebiasis), pathogenic bacteria in stool (Clostridium difficile, Shigella, Campylobacter, Yersinia, Salmonella, Listeria monocytogenes, Vibrio cholerae/parahemolyticus, verotoxin-producing E. coli)
• Anal lesions suggesting viral infection or positive test for HSV anal and/or multi-drug resistant bacteria (Enterobacteria producing extended spectrum betalactamase, Actinobacter baumanii, Vancomycin resistant enterococci and carbapenemase producing bacteria).
• Positive test for multidrug resistant bacteria
• If receiver is EBV negative, EBV positive donor will be excluded
• If receiver is CMV negative, CMV positive donor will be excluded.
• If receiver is negative for Toxoplasma gondii, positive donor for Toxoplasma gondii will be excluded
• Known transmissible infectious disease
• Infection (or possible infection) in the 7 days preceding screening
• Risk factors for Creutzfeldt-Jakob disease
• Personal history of Typhoid fever
• Gastrointestinal comorbidity

• Personal history or first degree relative :

• Inflammatory bowel disease
• Coeliac disease
• Personal history of irritable bowel syndrome, chronic constipation, chronic diarrhea
• Personal history of gastrointestinal neoplasia or polyposis
• First degree relative with gastrointestinal neoplasia or polyposis before 60 years old
• Gastrointestinal infection in the 3 preceding months (defined by the occurrence of an acute diarrhea that last less than a week)
• Factors possibly affecting the composition of the microbiota:

• Antibiotics or antifungic intake in the 3 preceding months before FT
• Non-steroidal anti inflammatory drugs (NSAIDs) intake in the 4 weeks preceding FT
• Specific diet (exclusion diet, vegetarian diet)
• Pregnancy
• Immunosuppressant intake (corticosteroids, calcineurin inhibitors, biologics, etc)
• Anti neoplastic chemotherapy
• Hemorrhoid disease
• Personal history or first degree relative with inflammatory or autoimmune disease
• Other Factors :

• Known chronic disease
• Abnormality at initial biological check up: blood cells count, fasting, glycaemia, kidney function, liver tests, haemostasis, calprotectin
• Long term curative therapy
• Recent intake of food allergens related of receiver's known allergy
• between screening and FT :

• At risk behavior (Travel, at risk sexual activity, blood transfusion, piercing tattoo, accidental blood exposure)
• Anal lesions suggestive of viral infection or positivity for HSV in anal area
• Infection or possible infection
• Occurrence of gastro-intestinal symptoms
• Medicine intake in the 48 hours preceding FT (except contraceptive)
• In case of woman: menstruation in the 48 hours preceding FT

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

ANRS, Emerging Infectious Diseases

OTHER_GOV

Sponsor Role: collaborator

Pierre and Marie Curie University

OTHER

Sponsor Role: collaborator

Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Harry Sokol, MD, PhD

Role: STUDY_DIRECTOR

Assistance Publique

Locations

Gastroenterology department, Saint Antoine Hospital

Paris, , France

Countries

France

References

Sokol H, Landman C, Seksik P, Berard L, Montil M, Nion-Larmurier I, Bourrier A, Le Gall G, Lalande V, De Rougemont A, Kirchgesner J, Daguenel A, Cachanado M, Rousseau A, Drouet E, Rosenzwajg M, Hagege H, Dray X, Klatzman D, Marteau P; Saint-Antoine IBD Network; Beaugerie L, Simon T. Fecal microbiota transplantation to maintain remission in Crohn's disease: a pilot randomized controlled study. Microbiome. 2020 Feb 3;8(1):12. doi: 10.1186/s40168-020-0792-5.

Reference Type: DERIVED

PMID: 32014035 (View on PubMed)

Other Identifiers

P 121104

Identifier Type: -

Identifier Source: org_study_id