Efficacy of microbiome manipulation strategies (fecAL microbial Transplantation OR CDED OR both) in combination standard medical therapy for induction and maintenance of remission in mild to moderate tReatment naÃive active Crohns Disease: a multicentre double-blind factorial randomized controlled trial(ALTER-CD)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 168
- 试验地点
- 7
- 主要终点
- 1.Proportion of patients with clinical remission (CDAI less than 150) and endoscopic response(decline in SES-CD by gretaer than 50%) at 10 weeks
研究概览
简要总结
Dysbiosis can be rectified by several methods: antibiotics, prebiotics, probiotics, dietary modulation, and fecal microbiota transplantation. There has been limited success with the isolated use of antibiotics and pre/probiotics in the treatment of IBD. Among the measures of dietary manipulation, the use of exclusive enteral nutrition (EEN) has shown superior, or at least equivalent, efficacy compared with steroids in pediatric CD. Although the results in adults are not as encouraging, recent cohort studies in patients with complicated CD have shown good success rates. Definite exclusion diets that exclude pro-inflammatory dietary constituents have also been tested with good clinical efficacy in patients with CD, who even failed treatment with anti-TNF agents. Various dietary approaches, inclusive of exclusive enteral nutrition, partial enteral nutrition, and Crohn’s disease exclusion diet have been reported to be of benefit and are associated with changes in gut microbiome.
Fecal microbiota transplantation (FMT) defined as the infusion of fecal suspension from a healthy individual into the gastrointestinal tract of an individual with GI disease carries a diverse population of microbiota and their metabolites and has been tested with varying efficacy in IBD. In general, FMT has shown good success rates in randomized control trials in patients with UC who failed conventional agents. Although limited small RCTs exist in CD, cohort studies have also shown good success rates. Therefore, the use of FMT in addition to standard medical therapy, is a concept that has not been previously explored and forms the basis for the present study. Therefore, a well-powered RCT is required to resolve the role of FMT in CD.
In this study, we will recruit patients in four arms. Group A includes FMT+CDED+SMT, in Group B FMT+SMT+SHAM DIET, in Group C Sham FMT+CDED+SMT, in Group D Sham FMT+ Sham Diet+ SMT given. 168 patients will be recruited across 6 centers for around 3 years. Follow-up of the patient will be done at 0,2,6 and 10 weeks and 8 weekly up to 48 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Patients with treatment-naive Crohns disease accessible with ileocolonoscopy
- •Symptom onset of less than 12 months
- •Mild to moderate disease activity with endoscopically active disease a.
- •CDAI of greater than 150 and less than 450 b.
- •SES-CD of or equal to or greater than 6 (or equal to or greater than 4 if isolated ileal disease)
- •Aged between 18-75 years.
排除标准
- •1.Patients with severe disease (CDAI greater than 450, SES-CD greater than 16) or requiring hospitalization
- •Patients who have been received on corticosteroids, immunosuppressants (azathioprine/ 6-mercaptoprine/methotrexate) for greater than 2 weeks
- •Biologicals or small molecule exposure
- •Stricturing (non-passable stricture), fistulising phenotype or perianal fistula/abscess
- •L4 disease
- •Pregnant or lactating women
- •Previous surgery for CD
- •Declining consent
- •Not willing for FMT/Dietary advise
- •Patients with current or recent history of clinically severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurological disease.
- •Positive assay or stool culture for pathogens (ova and parasite examination, bacteria) or positive test for Clostridioides difficile toxin at screening#
- •Patients infected with human immunodeficiency virus (HIV) # The patients with positive assay will be treated appropriately and tests will be repeated.
- •Those with negative assay and persistent activity will be included in the study.
结局指标
主要结局
1.Proportion of patients with clinical remission (CDAI less than 150) and endoscopic response(decline in SES-CD by gretaer than 50%) at 10 weeks
时间窗: 10 weeks and 48 weeks
2.Proportion of patients with clinical remission (CDAI less than 150) and endoscopic
时间窗: 10 weeks and 48 weeks
remission (SES-CD less than 3) at 48 weeks
时间窗: 10 weeks and 48 weeks
次要结局
- 1.Proportion of patients with clinical response defined as either CDAI decrease from(baseline of at least 70 points or CDAI less than 150 (10 weeks and 48 weeks))
研究者
Dr Vineet Ahuja
All India Institute of Medical Sciences New Delhi