Impact of Fecal transPlantAtion on MiCrobotia and hosT in Crohn's Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
- •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
- 另有 10 项未显示
研究组 & 干预措施
Fecal Transplantation
patients receiving the fecal transplant (fecal microbiota from a healthy donor)
干预措施: Fecal Transplantation (Other)
Sham Transplantation
patients receiving the vehicle (Physiological serum)
干预措施: Sham Transplantation (Other)
结局指标
主要结局
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.
时间窗: 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.
次要结局
- FT feasibility(6 weeks after FT)
- Clinical relapse rate in the 24 weeks following FT procedure(24 weeks following FT)
- Effect of FT compared to sham transplantation on CRP(6 weeks after FT)
- Effect of FT compared to sham transplantation on Leukocytes level(6 weeks after FT)
- Effect of FT compared to sham transplantation on fecal calprotectin(6 weeks after FT)
- 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 fecal microbiota composition(6 weeks after FT)
- 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 colon(6 weeks after FT)
- Effect of FT compared to sham transplantation on colon transcriptomics(6 weeks after FT)