Impact of the Fecal Flora Transplantation on Crohn's Disease (IMPACT-Crohn)

Assistance Publique - Hôpitaux de Paris

Status

Completed

Conditions

Crohn's Disease

Treatments

Other: Fecal Transplantation

Other: Sham Transplantation

Study type

Interventional

Funder types

Other

Identifiers

NCT02097797

P 121104

Details and patient eligibility

About

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.

Full 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.

Enrollment

24 patients

Sex

All

Ages

18 to 70 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

Receiver

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

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

Inclusion Criteria:

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:

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