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: A Multicenter Double Blind Factorial Randomized Controlled Trial(BOOST-CD)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 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 greater than 50%) at 10 weeks
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 4. Both the patient and the investigator will be blinded to the intervention.
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 active Crohn disease in whom FMT is feasible 2.Patients with an inadequate response, loss of response, or intolerance to conventional therapies (example, corticosteroids, immunomodulators, methotrexate) or advanced therapies (including but not limited to anti TNF alpha agents, anti integrins, anti IL 12 or IL 23 agents, anti IL 23 agents, JAK inhibitors).
- •The last administration of any such treatment must have occurred at least five half-lives prior to randomization 3.Aged between 18-75 years 4.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 7.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.
- •11.Positive assay or stool culture for pathogens (ova and parasite examination, bacteria) or positive test for Clostridioides difficile toxin at screening# 12.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 greater 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 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)(2.Proportion of patients with PRO2 Remission: at 10 weeks and 48 weeks)
研究者
Dr Vineet Ahuja
All India Institute of Medical Sciences New Delhi