Allogenic micobiota-reconstitution (AMR) for the treatment of patients with diarhea-predominant irritable bowel syndrome (IBS-D) - the AMIRA trial

肠道菌群的改变越来越被认为是肠易激综合征（ISS）发病机制和病理生理的主要参与者。病例报告显示同种异体微生物组重建（AMR）在肠易激综合征患者中的令人信服的效果。此外，AMR已被确定为复发性艰难梭菌感染的有效治疗方法，其副作用很小，并导致肠道微生物群的持久变化。在以腹泻为主的IBS （IBS- d）患者中进行AMR，我们的目标是通过将健康供者的粪便悬浮液注入患者的肠道，重建健康的肠道微生物群，从而减少相关症状并增加患者的健康。我们将对根据Rome III标准和IBS-QOL问卷诊断的IBS-D患者进行一项多中心、随机、盲法、安慰剂对照的AMR试验。供体材料的集中供应和质量控制将用于控制偏差。主要终点为IBS-SSS改善bb105分。次要终点包括IBS-QOL的变化，短期安全性和1年随访以控制长期效果和安全性。翻译程序包括AMR后供体微生物组的变化和接受，使用16S rna测序和定量多样性分析。结果将与主要终点的患者结果相关。随机化阶段之后是无应答者的开放标签交叉。我们期望AMR能显著减少IBS-0相关症状。

Alterations in gut microbiota are increasingly recognized as a major player in the pathogenesis and pathophysiology of irritable bowel syndrome (ISS). Case reports have shown convincing effects of allogenic microbiome reconstitution (AMR) in patients with IBS. Furthermore, AMR has been established as efficient treatment for recurrent C. difficile infection showing only minor side effects and resulting in durable changes of the gut microbiota. With AMR performed in patients with diarrhea predominant IBS (IBS-D) we aim to reduce related symptoms and to increase patient's well being by reestablishing a healthy intestinal microbiome through infusing stool suspension from healthy donors into the patient's intestine. We will perform a multicenter, randomized, blinded, placebo-controlled trial of AMR in patients with IBS-D diagnosed according to Rome III criteria and the IBS-QOL questionnaire. Central supply and quality control of donor material will be used to control bias. Primary endpoint is improvement of IBS-SSS by >105 points. Secondary endpoints include changes in IBS-QOL, short term safety and one year follow up to control lang term effects and safety. The translational program includes changes in, and acceptance of donor microbiome after AMR using 16S rONA sequencing and quantitative diversity analysis. Findings will be correlated with the patient outcome in the primary endpoint. The randomized phase is followed by an open label crossover for non-responders. We expect AMR to significantly reduce IBS-0 related symptoms.