Fecal Microbiota Transplantation in Severe Alcoholic Hepatitis- Assessment of Impact on Prognosis and Short-term Outcome
Primary Purpose
Severe Alcoholic Hepatitis
Status
Unknown status
Phase
Not Applicable
Locations
India
Study Type
Interventional
Intervention
Fecal Microbiota Transplantation
Standard of care treatment
Sponsored by
About this trial
This is an interventional treatment trial for Severe Alcoholic Hepatitis
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
- 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.
Sites / Locations
- Postgraduate Institute of Medical Education and ResearchRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Intervention Arm: Fecal microbiota transplantation
Control Arm
Arm Description
30 grams of stool homogenized with 100 mL of normal saline administered a single time via nasojejunal tube.
Nutritional supplementation, supportive management
Outcomes
Primary Outcome Measures
Survival
Secondary Outcome Measures
Improvement in CTP (Child Turcotte Pugh Score)
Improvement in MELD score
Improvement in MELDNa score
Improvement in CLIF SOFA score
Improvement in mDF
Changes in inflammatory markers (IL1b, IL6, TNF α) pre and post FMT,
Full Information
NCT ID
NCT03827772
First Posted
January 31, 2019
Last Updated
January 31, 2019
Sponsor
Postgraduate Institute of Medical Education and Research
1. Study Identification
Unique Protocol Identification Number
NCT03827772
Brief Title
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
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
January 2019 (Anticipated)
Primary Completion Date
December 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Postgraduate Institute of Medical Education and Research
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Alcoholic Hepatitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intervention Arm: Fecal microbiota transplantation
Arm Type
Experimental
Arm Description
30 grams of stool homogenized with 100 mL of normal saline administered a single time via nasojejunal tube.
Arm Title
Control Arm
Arm Type
Other
Arm Description
Nutritional supplementation, supportive management
Intervention Type
Other
Intervention Name(s)
Fecal Microbiota Transplantation
Intervention Description
30 grams of stool homogenized with 100 mL of normal saline administered a single time via nasojejunal tube.
Intervention Type
Other
Intervention Name(s)
Standard of care treatment
Intervention Description
Nutritional supplementation, supportive management.
Primary Outcome Measure Information:
Title
Survival
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Improvement in CTP (Child Turcotte Pugh Score)
Time Frame
3 months
Title
Improvement in MELD score
Time Frame
3 months
Title
Improvement in MELDNa score
Time Frame
3 months
Title
Improvement in CLIF SOFA score
Time Frame
3 months
Title
Improvement in mDF
Time Frame
3 months
Title
Changes in inflammatory markers (IL1b, IL6, TNF α) pre and post FMT,
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Radha K Dhiman, DM
Phone
7087009337
Email
rkpsdhiman@hotmail.com
Facility Information:
Facility Name
Postgraduate Institute of Medical Education and Research
City
Chandigarh
ZIP/Postal Code
160012
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Radha K Dhiman, DM
Phone
7087009337
Email
rkpsdhiman@hotmail.com
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35349076
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.
Results Reference
derived
Learn more about this trial
Fecal Microbiota Transplantation in Severe Alcoholic Hepatitis- Assessment of Impact on Prognosis and Short-term Outcome
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