Efficacy and Safety of Fecal Microbiota Transplant for Secondary Prophylaxis of Hepatic Encephalopathy: A Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Proportion of patients developing an episode of hepatic encephalopathy within 6 months
研究概览
简要总结
Despite standard of care, the recurrence of hepatic encephalopathy remains the primary cause for readmissions in individuals with cirrhosis. Patients with cirrhosis have disturbed gut microbiota, which is exacerbated by repeated antibiotic usage. FMT is a promising therapy to restore a healthy microbiota. FMT causes change in composition of gut microbiota which will lead to increase in commensal bacterial diversity which will increase colonization resistance to pathogenic bacteria and thereby decrease the bacterial overgrowth. Healthy bacteria also increase the SCFA production in colon with is and nutrient for endothelial cells and thereby protect the endothelial integrity and decreases bacterial translocation and endotoxemia. Current standard of care mainly focuses on the treatment of precipitating factors of the HE. The goal of our open-label, randomised clinical trial is to evaluate the safety, efficacy of addition of FMT to SOC in preventing subsequent episodes of hepatic encephalopathy.
详细描述
Hypothesis Engraftment of healthy donor microbiota in cirrhotic patients with hepatic encephalopathy curtails dysbiosis which subsequently prevent further episodes of hepatic encephalopathy and thereby increasing the transplant free survival
AIM:-To study efficacy and safety of fecal microbiota transplantation in preventing recurrence of hepatic encephalopathy in patients with cirrhosis who have recovered from first episode of hepatic encephalopathy
Methodology Study population: All cirrhotic patients between 18 years to 70 years, who have recovered within 7 days from hepatic encephalopathy after hospitalization.
Study design: A Randomized Controlled Trial Study period: December 2021- December 2022 Sample size: 66 (44:22 cases in each group) Randomization: The randomization will be done in 2:1 ratio by block randomization method with block size of 6. The allocation concealment will be done by using SNOSE method.
There are no Indian studies (RCT) available for suggesting role of FMT in hepatic encephalopathy.
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
- None
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
- •All cirrhotic patients between 18 years to 70 years, who have recovered within 7 days from hepatic encephalopathy after hospitalization
排除标准
- •Patient having hepatic encephalopathy after obvious precipitants (eg. diuretics, dehydration)
- •Patients on immunosuppressive medications
- •Active Infection (documented blood culture positive, Imaging diagnosis or SIRS>=1)
- •AKI (Defined as per KIDGO guidelines)
- •GI Bleed (In past 14 days)
- •Hepatocellular carcinoma
- •Patient with portosystemic shunt with size >10mm
- •Patients with previous TIPS or shunt surgery
- •Patients with significant comorbid illness such as heart, respiratory, or renal failure
- •Any neurologic diseases such as Alzheimer's disease, Parkinson's disease
- •Non hepatic metabolic encephalopathies
- •Not willing for the study
研究组 & 干预措施
FMT along with SMT
FMT + Standard medical therapy (SMT):
Lactulose (Titrated to 2-3 soft bowel movements per day) Oral LOLA can be used as an alternative or additional agent to treat patients non-responsive to conventional therapy Oral BCAAs can be used as an alternative or additional agent to treat patients non-responsive to conventional therapy Diet Daily energy intakes of 35-40 kcal/kg ideal body weight Daily protein intake 1.2-1.5 g/kg/day Small meals or liquid nutritional supplements evenly distributed throughout the day Oral BCAA supplementation in patient's intolerant of dietary protein (to allow recommended nitrogen intake to be achieved and maintained)
干预措施: Standard Medical Treatment (Other)
FMT along with SMT
FMT + Standard medical therapy (SMT):
Lactulose (Titrated to 2-3 soft bowel movements per day) Oral LOLA can be used as an alternative or additional agent to treat patients non-responsive to conventional therapy Oral BCAAs can be used as an alternative or additional agent to treat patients non-responsive to conventional therapy Diet Daily energy intakes of 35-40 kcal/kg ideal body weight Daily protein intake 1.2-1.5 g/kg/day Small meals or liquid nutritional supplements evenly distributed throughout the day Oral BCAA supplementation in patient's intolerant of dietary protein (to allow recommended nitrogen intake to be achieved and maintained)
干预措施: Fecal Microbiota Transplant (Other)
Standard Medical Treatment
Standard medical therapy (SMT):
Lactulose (Titrated to 2-3 soft bowel movements per day) Oral LOLA can be used as an alternative or additional agent to treat patients non-responsive to conventional therapy Oral BCAAs can be used as an alternative or additional agent to treat patients non-responsive to conventional therapy Diet Daily energy intakes of 35-40 kcal/kg ideal body weight Daily protein intake 1.2-1.5 g/kg/day Small meals or liquid nutritional supplements evenly distributed throughout the day Oral BCAA supplementation in patient's intolerant of dietary protein (to allow recommended nitrogen intake to be achieved and maintained)
干预措施: Standard Medical Treatment (Other)
结局指标
主要结局
Proportion of patients developing an episode of hepatic encephalopathy within 6 months
时间窗: 6 months
次要结局
- Change in urinary metabolomics pre and post FMT at baseline, 180 days(180 days)
- Change in Psychometric test/CFF pre and post FMT at day baseline,90 days(90 days)
- Change in inflammatory markers pre and post FMT at day baseline(0 day)
- Change in MELD score(180 days)
- Change in inflammatory markers pre and post FMT at 28 days(28 days)
- Change in inflammatory markers pre and post FMT at 90 days.(90 days)
- Change in urinary metabolomics pre and post FMT at baseline, 28 days(28 days)
- Change in Stool microbiome and metabolomics pre and post FMT at baseline, 28 days(28 days)
- Number of Participants with Transplant free survival at day 28(Day 28)
- Number of Participants with Transplant free survival at day 180(Day 180)
- Change in Ammonia level at day baseline, 28 days(28 days)
- Change in Psychometric test/CFF pre and post FMT at day baseline, 28 days(28 days)
- Change in Psychometric test/CFF pre and post FMT at day baseline, 180 days.(180 days)
- Change in Stool microbiome and metabolomics pre and post FMT at baseline, 90 days(90 days)
- Change in urinary metabolomics pre and post FMT at baseline, 90 days(90 days)
- Change in Stool microbiome and metabolomics pre and post FMT at baseline, 180 days(180 days)
- Proportion of patients developing adverse event related to FMT within 6 months(6 months)
- Number of Participants with Transplant free survival at day 90(Day 90)
- Change in Ammonia level pre and post FMT at day baseline,90 days(90 days)
- Change in CTP score(180 days)
- Change in Ammonia level pre and post FMT at day baseline, 180 days.(180 days)
- Change in inflammatory markers pre and post FMT at 180 days.(180 days)
- Change in MELD score(28 days)
- Change in CTP score(28 days)
- Change in CTP score(90 days)
- Change in MELD score(90 days)