Efficacy of Microbiome Manipulation Strategies (Fecal Microbial Transplant or Crohns Disease Exclusion Diet or Both) With Advanced Therapies (BiOlOgics and Small Molecules) to Break the Therapeutic Ceiling in Active Crohns Disease (BOOST-CD): A Multicenter Double Blind Factorial Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 168
- 试验地点
- 6
- 主要终点
- Proportion of patients with clinical remission and endoscopic response at week 10
研究概览
简要总结
Advanced therapies including biologics and small molecules target specific inflammatory pathways. IBD's multifactorial etiology means that blocking a single pathway may not be sufficient for all patients. Even when combination of advanced therapies are used, the incremental benefits often diminish, reflecting the therapeutic ceiling. Furthermore, safety concerns also limit the potential to push beyond this ceiling. Increasing the dose or adding more immunosuppressive agents can lead to a higher risk of infections, malignancies, and other adverse effects, making it impractical to continually intensify treatment. Understanding the therapeutic ceiling in IBD highlights the need for innovative approaches that go beyond current strategies. Given the diverse microbial and immunological landscapes in IBD combining fecal microbiota transplantation (FMT) and Crohn's Disease Exclusion Diet (CDED) with advanced therapies represents a promising approach to break the therapeutic ceiling in CD. This strategy leverages the complementary mechanisms of action of FMT/CDED and advance therapies, potentially offering a more comprehensive treatment modality that addresses the complex and multifactorial nature of IBD. FMT involves the transfer of gut microbiota from a healthy donor to a patient, aiming to restore a balanced microbial community in the intestines. This can help modulate the immune system and reduce inflammation, which are central to Crohn's disease pathology. This study seeks to provide evidence on whether addition of microbiota manipulation by FMT and CDED offers additional benefits when used alongside advance therapies in active CD. The findings from this RCT are expected to significantly enhance treatment strategies, ensuring that patients receive the most effective and appropriate care based on robust scientific evidence. This multi-center double blind placebo-controlled RCT will randomize patients in 1:1:1:1 ratio to FMT, CDED and advance therapy vs sham FMT with advance therapy and CDED vs FMT, Advance therapy and sham diet vs Advance therapy with sham FMT and sham diet for induction and maintenance of remission in patients of active Crohn's disease. Randomization will be held centrally to ensure concealment of allocation. Random numbers will be generated by computerized random number schedule (The RAND), and the randomization list and numbered packing of the intervention will be prepared by a person not involved in the study. Randomization will be performed using permuted blocks of 8. Both the patient and the investigator will be blinded to the intervention
详细描述
This is a multicenter, double-blind, factorial randomized controlled trial (RCT) evaluating the efficacy of microbiome manipulation strategies in patients with active Crohn's Disease (CD) undergoing advanced therapy (biologics or small molecules). The study will be conducted across six clinical centers in India, with an additional center designated for microbiome analysis.
Randomization and Blinding:
Randomization: Centralized, computer-generated randomization using permuted blocks of 8, 12, and 16 to ensure equal distribution across intervention arms.
Stratification: Not more than 1/3rd patients should be biological therapy exposed
Blinding:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with active Crohn disease in whom FMT is feasible
- •Active Crohn's disease who are candidates for advanced therapy (steroid refractory, Immunomodulator intolerant or refractory and moderately severe disease at the time of inclusion) or patients who have an intolerance to or have lost response to advanced therapies must have had their last treatment at least five half-lives prior randomization.
- •Aged between 18-75 years
- •CDAI greater than 150 and/or SES-CD equal or greater than 6 (or equal or greater than 4 if isolated ileal disease)
排除标准
- •Patients in remission (CDAI less than 150)
- •Stricturing disease (non-passable stricture) in whom FMT is not feasible
- •Fistulising phenotype or Perianal fistula or abscess
- •Isolated L4 disease
- •Active TB or Sepsis
- •Pregnant or lactating women
- •Patients with co-morbidities like CAD/CLD/CKD
- •Previous surgery for CD
- •Declining consent or not willing for FMT or diet advice
- •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
研究组 & 干预措施
Fecal microbiota transplantation(FMT) with Crohns disease exclusion diet (CDED) and advanced therapy
- FMT via colonoscopy at 0, 2 and 6 weeks (preceded by 3 days antibiotics, only before first procedure) followed by (if treatment responder) 8 weekly during maintenance till 42 weeks 2. Crohn disease exclusion diet(CDED) throughout the study 3. Advanced therapy as standard dose and schedule
干预措施: Fecal Microbial Transplantation (Other)
Fecal microbiota transplantation(FMT) with Crohns disease exclusion diet (CDED) and advanced therapy
- FMT via colonoscopy at 0, 2 and 6 weeks (preceded by 3 days antibiotics, only before first procedure) followed by (if treatment responder) 8 weekly during maintenance till 42 weeks 2. Crohn disease exclusion diet(CDED) throughout the study 3. Advanced therapy as standard dose and schedule
干预措施: Crohns Disease Exclusion Diet (Other)
Fecal microbiota transplantation(FMT) with Crohns disease exclusion diet (CDED) and advanced therapy
- FMT via colonoscopy at 0, 2 and 6 weeks (preceded by 3 days antibiotics, only before first procedure) followed by (if treatment responder) 8 weekly during maintenance till 42 weeks 2. Crohn disease exclusion diet(CDED) throughout the study 3. Advanced therapy as standard dose and schedule
干预措施: Advanced therapy (Other)
Fecal microbiota transplantation (FMT) with sham diet and Advanced therapy
- FMT via colonoscopy at 0, 2 and 6 weeks (preceded by 3 days antibiotics, only before first procedure) followed by (if treatment responder) 8 weekly during maintenance till 42 weeks 2. Dietary counselling throughout the study 3. Advanced therapy as standard dose and schedule
干预措施: Fecal Microbial Transplantation (Other)
Fecal microbiota transplantation (FMT) with sham diet and Advanced therapy
- FMT via colonoscopy at 0, 2 and 6 weeks (preceded by 3 days antibiotics, only before first procedure) followed by (if treatment responder) 8 weekly during maintenance till 42 weeks 2. Dietary counselling throughout the study 3. Advanced therapy as standard dose and schedule
干预措施: Sham Diet (Other)
Fecal microbiota transplantation (FMT) with sham diet and Advanced therapy
- FMT via colonoscopy at 0, 2 and 6 weeks (preceded by 3 days antibiotics, only before first procedure) followed by (if treatment responder) 8 weekly during maintenance till 42 weeks 2. Dietary counselling throughout the study 3. Advanced therapy as standard dose and schedule
干预措施: Advanced therapy (Other)
Sham FMT with Crohns disease exclusion diet (CDED) and advanced therapy
- Sham FMT with instillation of clean water at 0, 2 and 6 weeks (preceded by 3 days antibiotics, only before first procedure) followed by (if treatment responder) - 8- weekly during maintenance till 42 weeks 2. CDED throughout the study 3. Advanced therapy as standard dose and schedule
干预措施: Crohns Disease Exclusion Diet (Other)
Sham FMT with Crohns disease exclusion diet (CDED) and advanced therapy
- Sham FMT with instillation of clean water at 0, 2 and 6 weeks (preceded by 3 days antibiotics, only before first procedure) followed by (if treatment responder) - 8- weekly during maintenance till 42 weeks 2. CDED throughout the study 3. Advanced therapy as standard dose and schedule
干预措施: Sham transplantation (Other)
Sham FMT with Crohns disease exclusion diet (CDED) and advanced therapy
- Sham FMT with instillation of clean water at 0, 2 and 6 weeks (preceded by 3 days antibiotics, only before first procedure) followed by (if treatment responder) - 8- weekly during maintenance till 42 weeks 2. CDED throughout the study 3. Advanced therapy as standard dose and schedule
干预措施: Advanced therapy (Other)
Sham Diet with Sham FMT with advance therapy
1.Sham FMT with instillation of clean water at 0, 2 and 6 weeks (preceded by 3 days antibiotics, only before first procedure) followed by (if treatment responder) - 8- weekly during maintenance till 42 weeks 2. Dietary counselling throughout the study 3. Advanced therapy as standard dose and schedule.
干预措施: Sham transplantation (Other)
Sham Diet with Sham FMT with advance therapy
1.Sham FMT with instillation of clean water at 0, 2 and 6 weeks (preceded by 3 days antibiotics, only before first procedure) followed by (if treatment responder) - 8- weekly during maintenance till 42 weeks 2. Dietary counselling throughout the study 3. Advanced therapy as standard dose and schedule.
干预措施: Sham Diet (Other)
Sham Diet with Sham FMT with advance therapy
1.Sham FMT with instillation of clean water at 0, 2 and 6 weeks (preceded by 3 days antibiotics, only before first procedure) followed by (if treatment responder) - 8- weekly during maintenance till 42 weeks 2. Dietary counselling throughout the study 3. Advanced therapy as standard dose and schedule.
干预措施: Advanced therapy (Other)
结局指标
主要结局
Proportion of patients with clinical remission and endoscopic response at week 10
时间窗: 10 weeks
Proportion of patients with clinical remission (defined as CDAI less than 150) and endoscopic response( defined decline in SES-CD by greater than 50%)
Proportion of patients with clinical remission and endoscopic remission at week 10
时间窗: 48 weeks
Proportion of patients with clinical remission (defined as Crohn's disease activity index less than 150) and endoscopic remission (defined as Simple Endoscopic Score for Crohn's disease patients less than 3)
次要结局
- Proportion of patients with clinical response at Week 10(10 weeks)
- Proportion of patients with PRO2 Remission at Week 10(10 weeks)
- Proportion of patients with endoscopic response at Week 10(10 weeks)
- Fecal microbiome and metabolite signature between responders and non-responders at week 10(10 weeks)
- Proportion of patients with biomarker remission at Week 10(10 weeks)
- Proportion of patients with adverse events at Week 10(10 weeks)
- Proportion of patients with clinical response at Week 48(48 weeks)
- Proportion of patients with PRO2 remission at Week 48(48 weeks)
- Proportion of patients with endoscopic response at Week 48(48 weeks)
- Proportion of patients with Endoscopic remission at Week 48 weeks(48 weeks)
- Proportion of patients with corticosteroid-free clinical remission at Week 48(48 weeks)
- Fecal microbiome and metabolite signature between responders and non-responders at Week 48(48 weeks)
- Proportion of patients with biomarker remission at Week 48(48 weeks)
- Proportion of patients with adverse event at Week 48(48 weeks)
- Proportion of patients with adverse event at Week 6(6 weeks)
- Proportion of Patients Experiencing Adverse Events at Week 26(26 weeks)
研究者
Prof. Vineet Ahuja
Professor
All India Institute of Medical Sciences, New Delhi