Clinical trial NCT03827772: Fecal Microbiota Transplantation in Severe Alcoholic Hepatitis- Assessment of Impact on Prognosis and Short-term Outcome
Official title: Fecal Microbiota Transplantation in Severe Alcoholic Hepatitis- Assessment of Impact on Prognosis and Short-term Outcome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Severe Alcoholic Hepatitis
Lead sponsor: PGIMER
Sponsor class: UNKNOWN
First posted: 2019-02-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Severe alcoholic hepatitis will be defined as proposed by the American College of Gastroenterology

  1. Rapid development or worsening of jaundice and liver-related complications with serum total bilirubin more than 3 milligrams per decilitre.
  2. 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 1.5.
  3. Documentation of persistent heavy alcohol use until 8 weeks before onset of symptoms.
  4. 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.
  5. Maddrey's Discriminant Function Score of more than 32 OR
  6. A patient of alcoholic hepatitis who will present with grade 1 or 2 of hepatic encephalopathy.

Exclusion Criteria:

1. Intestinal paralysis, lack of bowel sounds, intestinal perforation.
2. Uncontrolled infections.
3. Uncontrolled upper gastrointestinal bleeding.
4. Grade 3,4 hepatic encephalopathy.
5. Hepatic or extrahepatic malignancy.
6. Maddrey's Discriminant Function (mDF) \>90 or MELD\>30.
7. Autoimmune hepatitis, Wilson's disease, suspected drug induced liver injury.
8. Patients who are aged \>60 years
9. WBC count \<1000 cells/mm3
10. Pregnancy or nursing.
11. Human Immunodeficiency Virus (HIV), HBV, HCV infection.
12. Patient's unwillingness to participate in the study.
13. Any other condition which, in the opinion of the investigator, would impede compliance or hinder completion of the study.

Primary outcomes:
measure: Survival
timeFrame: 3 months
Secondary outcomes:
measure: Improvement in CTP (Child Turcotte Pugh Score)
timeFrame: 3 months
measure: Improvement in MELD score
timeFrame: 3 months
measure: Improvement in MELDNa score
timeFrame: 3 months
measure: Improvement in CLIF SOFA score
timeFrame: 3 months
measure: Improvement in mDF
timeFrame: 3 months
measure: Changes in inflammatory markers (IL1b, IL6, TNF α) pre and post FMT,
timeFrame: 3 months
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education and Research
Study officials:
References:
citation: Sharma A, Roy A, Premkumar M, Verma N, Duseja A, Taneja S, Grover S, Chopra M, Dhiman RK. Fecal microbiota transplantation in alcohol-associated acute-on-chronic liver failure: an open-label clinical trial. Hepatol Int. 2022 Apr;16(2):433-446. doi: 10.1007/s12072-022-10312-z. Epub 2022 Mar 28.