The Effect of Probiotics on Hemodynamic Changes and Complications of Cirrhosis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- the change in cardiac output
研究概览
简要总结
This is a single-center blinded randomized interventional placebo-controlled study of the effect of probiotics on hemodynamic parameters and liver function in cirrhosis.
详细描述
Forty patients with Child-Pugh class B and C cirrhosis will be randomized in a 1.5:1 ratio to test and control arms. Patients in the test arm will receive probiotic Saccharomyces boulardii (A07FA02 - Saccharomyces (Enterol) Biocodex Ltd, France, registration number LP-000622 from 21.09.2011) for 3 months, patients in the control arm will receive placebo for 3 months. All patients also will receive standard treatment: spironolactone 100 mg/day in ascites and carvedilol 12.5 mg/day in esophageal varices. The patients will be blinded. At inclusion and after 3 months after starting of probiotic/placebo treatment, systemic hemodynamics parameters (cardiac output and systemic vascular resistance), liver function (serum albumin and total bilirubin level, international normalized ratio, presence and degree of ascites or hepatic encephalopathy), the gut microbiome, biomarkers of bacterial translocation (presepsin, lipopolysaccharide), intestinal permeability (claudin 3), systemic inflammation (tumor necrosis factor alpha ) and endothelial dysfunction (nitrites, endothelin) will be assessed. After the end of the study, an interim analysis of the effect of the probiotic on aforementioned systemic hemodynamics and liver function indicators will be carried out. If there is a positive effect, a full analysis of all the aforementioned factors contributing to its development will be performed.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cirrhosis
- •Child-Pugh class B or C;
- •Age between 18 and 70 years;
- •Signed informed consent.
排除标准
- •Use of lactulose, lactitol, or other prebiotics, probiotics, antibiotics, or metformin in the past 6 weeks before inclusion;
- •Alcohol consumption in the past 6 weeks before inclusion;
- •Inflammatory bowel disease;
- •Prematurely discontinuation of the consumption of tested probiotic/placebo;
- •Started taking antibiotics, other probiotics, or prebiotics during the follow-up period;
- •Refusal to participate during the follow-up period.
研究组 & 干预措施
Probiotics
Patients in the Test arm will receive Saccharomyces boulardii (Saccharomyces), (Enterol), Biocodex Ltd, France, registration number LP-000622 from 21.09.2011 at a dose of 250 mg 2 times a day for 3 months.
干预措施: Saccharomyces Boulardii Probiotic Supplement (Drug)
Placebo
Patients in the Placebo arm will receive the placebo at a dose of 250 mg 2 times a day for 3 months.
干预措施: Placebo (Drug)
结局指标
主要结局
the change in cardiac output
时间窗: at inclusion and 3 months after the start of the study
Transthoracic echocardiography (with Acuson S2000 by Siemens Ltd, USA, registration number 2017/6109 from 24.07.2018) according to the guidelines of the American Society of Echocardiography (published in 2015) with a simultaneous assessment of blood pressure (with semi-automatic tonometer UA-604 by AND Ltd, Japan, registration number 2011/09642 from 10.10.2018) and heart rate will be performed to assess systemic hemodynamics. Cardiac output will be calculated as (stroke volume) × (heart rate).
the change in number of points on the Child-Pugh scale
时间窗: at inclusion and 3 months after the start of the study
The scale assesses the degree of hyperbilirubinemia (1 point - serum total bilirubin level is less than 2 mg / dl, 2 points - 2-3 mg / dl, 3 points - above 3 mg / dl), hypoalbuminemia (1 point - serum albumin level above 35 g / l, 2 points - 28-35 g / l, 3 points - less than 28 g / l), hypocoagulation (1 point - international normalized ratio less than 1.7, 2 points - 1.7-2.3, 3 points - above 2.3) degree of ascites (1 points - no ascites, 2 points - ascites detected only with ultrasound, 3 points - large ascites visible to the eyes) of hepatic encephalopathy (1 point - no hepatic encephalopathy; 2 points - hepatic encephalopathy without severe manifestations (stupor or coma); 3 points - severe hepatic encephalopathy (stupor or coma)).
次要结局
- the change in the serum albumin level(at inclusion and 3 months after the start of the study)
- the change in the degree of hepatic encephalopathy(at inclusion and 3 months after the start of the study)
- the change in the presence of small intestinal bacterial overgrowth(at inclusion and 3 months after the start of the study)
- the change in the serum lipopolysaccharide level(at inclusion and 3 months after the start of the study)
- the change in the serum C-reactive protein level(at inclusion and 3 months after the start of the study)
- the change in the serum presepsin level(at inclusion and 3 months after the start of the study)
- the change in the serum total bilirubin level(at inclusion and 3 months after the start of the study)
- the change in the international normalized ratio(at inclusion and 3 months after the start of the study)
- the change in the degree of ascites(at inclusion and 3 months after the start of the study)
- the change in systemic vascular resistance(at inclusion and 3 months after the start of the study)
- the change in the serum claudin 3 level(at inclusion and 3 months after the start of the study)
- the change in the serum nitrites level(at inclusion and 3 months after the start of the study)
- the change in the serum tumor necrosis factor alpha level(at inclusion and 3 months after the start of the study)
- the change in the serum big endothelin level(at inclusion and 3 months after the start of the study)