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临床试验/NCT03827772
NCT03827772Unknown不适用

Fecal Microbiota Transplantation in Severe Alcoholic Hepatitis- Assessment of Impact on Prognosis and Short-term Outcome

Post Graduate Institute of Medical Education and Research, Chandigarh2 个研究点 分布在 1 个国家目标入组 40 人开始时间: 2019年1月1日最近更新:
适应症
干预措施

试验速览

阶段
不适用
发起方
入组人数
40
试验地点
2
主要终点
Survival

研究概览

简要总结

Alcoholic liver disease has become one of the foremost causes of chronic liver disease across the world, and a cause of considerable morbidity and mortality. Alcoholic steatohepatitis is an entity in this broad spectrum, with severe alcoholic hepatitis transitioning to acute on chronic liver failure carrying a one month mortality of as high as 20 to 50%.

The current management guidelines for severe alcoholic hepatitis show benefit with prolonged alcohol abstinence, nutritional support, the use of corticosteroids, pentoxifylline or N-acetyl cysteine (NAC) and early liver transplantation. However, major studies and meta-analyses have demonstrated that these interventions, with the exception of early liver transplantation, do not improve mortality rates to the level of statistical significance. Owing to the high short term mortality associated with severe alcoholic hepatitis, the inadequacy of a treatment that could significantly impact this short term mortality, and the limited applicability of early liver transplantation, a study on newer modalities of treatment is warranted.

The role that human gut microbiota plays in health and disease is receiving considerable attention. Targeting intestinal dysbiosis, a phenomenon found to be intricately linked with the causation of alcoholic hepatitis, could provide insights into novel therapeutic strategies.

Fecal microbiota transplantation is a novel approach that has gained widespread acceptance in in the management of recurrent severe Clostridium difficile infection. It's role is also being studied in other diseases where an association with gut dysbiosis has been found, such as in inflammatory bowel disease and irritable bowel syndrome. The role of FMT has also been studied in liver diseases such as non-alcoholic fatty liver disease (NAFLD), liver cirrhosis and primary sclerosing cholangitis. In this process, a diseased recipient is transferred fecal material containing the microflora of a healthy individual. It limits the colonization of pathogens, inducing colonization resistance, affects microbiota composition in the gut, as well as metabolism in the microbial pathogens. FMT helps alleviate gut dysbiosis and restores gut microbial diversity.

Our aim is to evaluate the role of FMT on short term survival and improvement in scores of prognostic significance (CTP, MELD, MELDNa, mDF) in patients with severe alcoholic hepatitis.

研究设计

研究类型
Interventional
分配方式
Non 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 60 Years(Adult)
性别
All
接受健康志愿者

入选标准

  • Severe alcoholic hepatitis will be defined as proposed by the American College of Gastroenterology
  • Rapid development or worsening of jaundice and liver-related complications with serum total bilirubin more than 3 milligrams per decilitre.
  • Aspartate aminotransferase and alanine aminotransferase elevated to more than one and half times the upper limit of normal, but less than 400 IU per litre, with AST to ALT ratio over 1.
  • Documentation of persistent heavy alcohol use until 8 weeks before onset of symptoms.
  • Alcohol Consumption in female over 40 grams per day for at least 6 months and in males over 60 grams per day for at least 6 months.
  • Maddrey's Discriminant Function Score of more than 32 OR
  • A patient of alcoholic hepatitis who will present with grade 1 or 2 of hepatic encephalopathy.

排除标准

  • Intestinal paralysis, lack of bowel sounds, intestinal perforation.
  • Uncontrolled infections.
  • Uncontrolled upper gastrointestinal bleeding.
  • Grade 3,4 hepatic encephalopathy.
  • Hepatic or extrahepatic malignancy.
  • Maddrey's Discriminant Function (mDF) >90 or MELD>
  • Autoimmune hepatitis, Wilson's disease, suspected drug induced liver injury.
  • Patients who are aged >60 years
  • WBC count <1000 cells/mm3
  • Pregnancy or nursing.
  • Human Immunodeficiency Virus (HIV), HBV, HCV infection.
  • Patient's unwillingness to participate in the study.
  • Any other condition which, in the opinion of the investigator, would impede compliance or hinder completion of the study.

研究组 & 干预措施

Intervention Arm: Fecal microbiota transplantation

Experimental

30 grams of stool homogenized with 100 mL of normal saline administered a single time via nasojejunal tube.

干预措施: Fecal Microbiota Transplantation (Other)

Control Arm

Other

Nutritional supplementation, supportive management

干预措施: Standard of care treatment (Other)

结局指标

主要结局

Survival

时间窗: 3 months

次要结局

  • Changes in inflammatory markers (IL1b, IL6, TNF α) pre and post FMT,(3 months)
  • Improvement in MELD score(3 months)
  • Improvement in MELDNa score(3 months)
  • Improvement in CTP (Child Turcotte Pugh Score)(3 months)
  • Improvement in CLIF SOFA score(3 months)
  • Improvement in mDF(3 months)

研究者

发起方
Post Graduate Institute of Medical Education and Research, Chandigarh
申办方类型
Other
责任方
Principal Investigator
主要研究者

Radha K Dhiman

Professor and Head, Department of Hepatology

Post Graduate Institute of Medical Education and Research, Chandigarh

研究点 (2)

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