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

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ClinicalTrials.gov Identifier: NCT03827772
Recruitment Status : Recruiting
First Posted : February 1, 2019
Last Update Posted : February 1, 2019
Sponsor:
Information provided by (Responsible Party):
Radha K Dhiman, Postgraduate Institute of Medical Education and Research

Tracking Information
First Submitted Date  ICMJE January 31, 2019
First Posted Date  ICMJE February 1, 2019
Last Update Posted Date February 1, 2019
Estimated Study Start Date  ICMJE January 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 31, 2019)
Survival [ Time Frame: 3 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2019)
  • Improvement in CTP (Child Turcotte Pugh Score) [ Time Frame: 3 months ]
  • Improvement in MELD score [ Time Frame: 3 months ]
  • Improvement in MELDNa score [ Time Frame: 3 months ]
  • Improvement in CLIF SOFA score [ Time Frame: 3 months ]
  • Improvement in mDF [ Time Frame: 3 months ]
  • Changes in inflammatory markers (IL1b, IL6, TNF α) pre and post FMT, [ Time Frame: 3 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Fecal Microbiota Transplantation in Severe Alcoholic Hepatitis- Assessment of Impact on Prognosis and Short-term Outcome
Official Title  ICMJE Fecal Microbiota Transplantation in Severe Alcoholic Hepatitis- Assessment of Impact on Prognosis and Short-term Outcome
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Severe Alcoholic Hepatitis
Intervention  ICMJE
  • Other: Fecal Microbiota Transplantation
    30 grams of stool homogenized with 100 mL of normal saline administered a single time via nasojejunal tube.
  • Other: Standard of care treatment
    Nutritional supplementation, supportive management.
Study Arms  ICMJE
  • Experimental: Intervention Arm: Fecal microbiota transplantation
    30 grams of stool homogenized with 100 mL of normal saline administered a single time via nasojejunal tube.
    Intervention: Other: Fecal Microbiota Transplantation
  • Control Arm
    Nutritional supplementation, supportive management
    Intervention: Other: Standard of care treatment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 31, 2019)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Radha K Dhiman, DM 7087009337 rkpsdhiman@hotmail.com
Listed Location Countries  ICMJE India
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03827772
Other Study ID Numbers  ICMJE PGIMER Hepatology
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Radha K Dhiman, Postgraduate Institute of Medical Education and Research
Study Sponsor  ICMJE Postgraduate Institute of Medical Education and Research
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Postgraduate Institute of Medical Education and Research
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP