NCT03827772

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
40

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Jan 2019

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2019

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

January 31, 2019

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 1, 2019

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2019

Completed
Last Updated

February 1, 2019

Status Verified

January 1, 2019

Enrollment Period

11 months

First QC Date

January 31, 2019

Last Update Submit

January 31, 2019

Conditions

Severe Alcoholic Hepatitis

Outcome Measures

Primary Outcomes (1)

  • Survival

    3 months

Secondary Outcomes (6)

  • Improvement in CTP (Child Turcotte Pugh Score)

    3 months

  • Improvement in MELD score

    3 months

  • Improvement in MELDNa score

    3 months

  • Improvement in CLIF SOFA score

    3 months

  • Improvement in mDF

    3 months

  • +1 more secondary outcomes

Study Arms (2)

Intervention Arm: Fecal microbiota transplantation

EXPERIMENTAL

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

Other: Fecal Microbiota Transplantation

Control Arm

OTHER

Nutritional supplementation, supportive management

Other: Standard of care treatment

Interventions

Fecal Microbiota TransplantationOTHER

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

Intervention Arm: Fecal microbiota transplantation
Standard of care treatmentOTHER

Nutritional supplementation, supportive management.

Control Arm

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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 1.5.
  • 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.

You may not qualify if:

  • 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\>30.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Postgraduate Institute of Medical Education and Research

Chandigarh, 160012, India

RECRUITING

Related Publications (1)

  • 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.

    PMID: 35349076DERIVED

MeSH Terms

Conditions

Hepatitis, Alcoholic

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

HepatitisLiver DiseasesDigestive System DiseasesLiver Diseases, AlcoholicAlcohol-Induced DisordersAlcohol-Related DisordersSubstance-Related DisordersChemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Biological TherapyTherapeutics

Central Study Contacts

Radha K Dhiman, DM

CONTACT

7087009337rkpsdhiman@hotmail.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor and Head, Department of Hepatology

Study Record Dates

First Submitted

January 31, 2019

First Posted

February 1, 2019

Study Start

January 1, 2019

Primary Completion

December 1, 2019

Study Completion

December 1, 2019

Last Updated

February 1, 2019

Record last verified: 2019-01

Data Sharing

IPD Sharing
Will not share

Locations

IN(1)