Faecal Microbiota Transplantation to Prevent Complications, Progression and Mortality of Liver Cirrhosis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- Time to death or new episode of acute decompensation requiring intervention in FMT versus placebo-treated patients.
研究概览
简要总结
The purpose is to investigate the effect of faecal microbiota transplantation (FMT) on complications, progression, and mortality of patients with liver cirrhosis. Further, the investigators want to examine the impact of FMT on the gut microbiota, gut barrier function, systemic inflammation, and immune function.
详细描述
Patients with liver disease have a disturbed gut microbiota. This is often associated with disease progression and development of complications, so-called episodes of decompensation. In this trial, we will change the microbiota of these patients by transferring a healthy microbiota through faeces from a healthy donor, a procedure known as faecal microbiota transplantation (FMT). We will examine the effect of FMT on the prognosis and disease progression of the patients. Further, we will examine the mechanistic effects of FMT. We will at random divide 220 patients admitted with decompensation of liver cirrhosis evenly into two groups. One group will receive FMT and the other group will receive placebo. After the treatment, we will follow the patients for one year and examine disease progression as well as changes in their gut microbiota, gut barrier, and immune function.
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
- Triple (Participant, Investigator, Outcomes Assessor)
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
- •Age 18-75 years
- •Liver cirrhosis with Child-Pugh ≤ 12
- •Acute decompensation requiring intervention (ascites, gastrointestinal bleeding, infections leading to progressive liver failure, overthepatic encephalopathy, alcoholic hepatitis)
排除标准
- •More than one organ failure defined by CLIF-SOFA score
- •Untreated malignancy apart from non-melanoma skin cancer
- •Untreated viral hepatitis
- •Inflammatory bowel disease
- •Celiac disease
- •Clostridioides Difficile infection
- •Pregnancy
- •Unable to participate based on medical judgement
研究组 & 干预措施
Faecal microbiota transplantation
The patients will receive three applications of FMT consisting of 50 g cryopreserved, homogenized faeces from healthy donors. The faecal material will be dispensed into double-coated, acid-resistant enterocapsules or cryobags. Faeces will be screened according to international guidelines.
干预措施: Faecal microbiota transplantation (Biological)
Placebo
The placebo products is produced from a suspension of glycerol, saline and food colouring and cannot be distinguished from the active FMT products.
干预措施: Placebo (Biological)
结局指标
主要结局
Time to death or new episode of acute decompensation requiring intervention in FMT versus placebo-treated patients.
时间窗: 1 year
Using data from the patient journals, we will be able to examine the exact time to event in each of the patients. To compare the two groups, hazard ratios will be calculated.
次要结局
- Time to death or new episode of acute decompensation requiring intervention in FMT versus placebo-treated patients at 3 months and 6 months of follow-up.(3 months, 6 months)
- Number of new decompensations and deaths during follow-up in the FMT versus the placebo-treated patients.(1 year)
- Time to death in FMT versus placebo-treated patients. -treated patients at 3 months and 6 months of follow-up.(1 year, 6 months, 3 months)
- Change in gut microbiota beta-diversity (Bray-Curtis index) during one year in FMT versus placebo-treated patients by shotgun metagenomic sequencing.(1 year, 6 months, 3 months)
- Change in disease severity in FMT- versus placebo-treated patients.(3 months, 6 months, 1 year.)
- Change in plasma concentration of gut translocation markers; lipopolysaccharide binding protein, soluble CD14, fatty acid binding protein 1 during one year in FMT versus placebo-treated patients by ELISA.(1 year, 6 months, 3 months)
- Change in plasma and stool concentration of pro- and antiinflammatory cytokines; IL-6, IL-1beta, TNF-alpha, IL-8, IL-10 in response to the intervention by luminex.(1 year, 6 months, 3 months)
- Change in metabolic liver function in FMT- versus placebo-treated patients.(3 months, 6 months, 1 year.)
- Change in liver stiffness in FMT- versus placebo-treated patients.(3 months, 6 months, 1 year.)
- Change in the Liver Frailty Index in FMT- versus placebo-treated patients.(3 months, 6 months, 1 year.)
- Change in body composition in FMT- versus placebo-treated patients.(3 months, 6 months, 1 year.)
- Change in cognitive function as measured by continuous reaction time in FMT- versus placebo-treated patients.(3 months, 6 months, 1 year.)
- Change in cognitive function in FMT- versus placebo-treated patients.(3 months, 6 months, 1 year.)
- Change in quality adjusted life years (QALY´s) to evalute health care related costs in FMT- versus placebo-treated patients(1 year)