Crohn's Disease
Conditions
Keywords
Inflammatory bowel disease, Crohn's disease, microbiota, fecal transplantation
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.
Interventions
Fecal microbiota (50-100g of stool from donor resuspended in 250-350ml of physiological serum and filtered) given by infusion in coecum during colonoscopy
OTHERSham Transplantation
250-350ml of physiological serum given by infusion in coecum during colonoscopy
Sponsors
ANRS, Emerging Infectious Diseases
Pierre and Marie Curie University
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| FT success defined by : Sorensen's index [receiver 6 weeks after FT vs donor] > Sorensen's index [receiver 6 weeks after FT vs receiver before FT]) with Sorensen's index [receiver 6 weeks after FT vs donor] ≥ 0.6. | 6 weeks after FT | In other words, FT success is reached if the fecal microbiota of the receiver 6 weeks after FT is closer of the fecal microbiota of the donor that of the receiver before FT. Fecal microbiota composition will be assessed by 454 pyrosequencing (16S RNA) and microbiota comparison will be done using Sorensen's index. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FT feasibility | 6 weeks after FT | evaluate the feasibility of the FT procedure (frequency of evaluable patients in each group) |
| Clinical relapse rate in the 24 weeks following FT procedure | 24 weeks following FT | Clinical relapse defined by a Crohn's disease activity index (CDAI) \> 220 points, or by a CDAI between 150 and 220 with an increase \>70 compared with baseline, or by the need of surgery or to start a medical treatment for CD. |
| Effect of FT compared to sham transplantation on CRP | 6 weeks after FT | Effect of FT compared to sham transplantation on CRP level. |
| Effect of FT compared to sham transplantation on Leukocytes level | 6 weeks after FT | Effect of FT compared to sham transplantation on: Leukocytes level |
| Effect of FT compared to sham transplantation on fecal calprotectin | 6 weeks after FT | Effect of FT compared to sham transplantation on: fecal calprotectin |
| Effect of FT compared to sham transplantation on fecal microbiota composition | 6 weeks after FT | Effect of FT compared to sham transplantation on: fecal microbiota composition |
| Effect of FT compared to sham transplantation on lymphocytes population in blood | 6 weeks after FT | Effect of FT compared to sham transplantation on: lymphocytes population in blood |
| Effect of FT compared to sham transplantation on lymphocytes population in colon | 6 weeks after FT | Effect of FT compared to sham transplantation on: lymphocytes population in colon. |
| Effect of FT compared to sham transplantation on colon transcriptomics | 6 weeks after FT | Effect of FT compared to sham transplantation on: colon transcriptomics. |
| Effect of FT compared to sham transplantation on Crohn's Disease Endoscopic Index of Severity | 6 weeks after FT | Effect of FT compared to sham transplantation on: Crohn's Disease Endoscopic Index of Severity |
Countries
France
Outcome results
None listed