Probiotic Modulation of Gut Microflora in Cirrhosis: Influence on Immune Function and Infections
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 92
- 试验地点
- 2
- 主要终点
- Change in neutrophil phagocytic capacity
研究概览
简要总结
Liver cirrhosis is the 10th most common cause of death in the western world. Infection is the most common precipitant of deterioration of liver function in cirrhosis. Endotoxin, derived from gram-negative organisms in the gut, can enter the circulation due to increased gut permeability and contributes to neutrophil dysfunction, infection risk and mortality in alcoholic cirrhotics. As probiotics decrease gram-negative organisms in the gut and/or decrease gut permeability, the investigators hypothesize that probiotic treatment would restore neutrophil function and prevent infection in alcoholic cirrhosis.
The investigators hypothesize that administration of a probiotic mixture in patients with liver cirrhosis will improve innate immune function through alteration of the gut bacterial flora and gut barrier integrity.
The aim of this randomised, double-blinded placebo-controlled study is to assess whether food supplementation with probiotic mixture improves neutrophil phagocytic capacity in patients with cirrhosis and decreases the incidence of significant infections.
92 patients with alcoholic cirrhosis will be included according to a sample size calculation from preliminary data. Patients will be randomized in two groups: Group 1 receives a probiotic mixture Group 2 receives a similar looking and tasting placebo without bacteria. The recruited patients will be treated for 6 months. Besides routine clinical and laboratory assessments, neutrophil function, toll-like receptor expression, endotoxin levels, bacterial DNA, cytokine levels, albumin oxidation, gut permeability and analysis of gut microflora will be performed. Furthermore nutritional status and quality of life will be assessed.
Primary endpoints will be neutrophil phagocytosis. Secondary endpoints will be significant infection, neutrophil oxidative burst, neutrophil toll-like receptor expression, endotoxin levels, bacterial DNA; cytokine levels, albumin oxidation, gut barrier function and bacterial flora, nutritional status and quality of life.
If our hypothesis holds true, probiotics will provide an easily applicable and cost effective method to improve immune function and to prevent infection in liver cirrhosis. It is possible that this can improve survival of patients with liver cirrhosis.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged between 18-80 years
- •Clinical and radiological evidence of cirrhosis, and/or biopsy proven liver cirrhosis of any cause
- •Informed consent
排除标准
- •Child-Pugh score > 11
- •Abstinence from alcohol for < 2 weeks at the time of screening for inclusion
- •Clinical evidence of active infection
- •Antibiotic treatment within 7 days prior to enrolment
- •Gastrointestinal haemorrhage within previous 2 weeks
- •Use of immunomodulating agents within previous month (steroids etc.)
- •Use of proton pump inhibitors for preceding two weeks
- •Concomitant use of supplements (pre-, pro-, or synbiotics) likely to influence the study
- •Renal failure (such as hepatorenal syndrome), creatinine >1.7 mg/dL
- •Hepatic encephalopathy II to IV
- •Pancreatitis
- •Other organ failure
- •Hepatic or extra-hepatic malignancy
- •Pregnancy
- •Presumed non-compliance to the study medication
结局指标
主要结局
Change in neutrophil phagocytic capacity
时间窗: Change from baseline to 6 months
Percentage of neutrophil granulocytes showing phagocytosis of FITC (fluorescein isothiocyanate) -labelled E.coli bacteria
次要结局
- albumin oxidation(0, 6, 12 months)
- inflammatory response(0, 6, 12 months)
- neutrophil toll like receptor expression(0, 6, 12 months)
- Number of clinically significant infections(during 12 months)
- nutritional status(0,6, 12 months)
- endotoxin levels(0, 6, 12 months)
- changes in gut permeability over time(0, 6, 12 months)
- neutrophil oxidative burst(0, 6, 12 months)
- bacterial flora(0, 6, 12 months)
- quality of life(0, 6, 12 months)