<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03827772</url>
  </required_header>
  <id_info>
    <org_study_id>PGIMER Hepatology</org_study_id>
    <nct_id>NCT03827772</nct_id>
  </id_info>
  <brief_title>Fecal Microbiota Transplantation in Severe Alcoholic Hepatitis- Assessment of Impact on Prognosis and Short-term Outcome</brief_title>
  <official_title>Fecal Microbiota Transplantation in Severe Alcoholic Hepatitis- Assessment of Impact on Prognosis and Short-term Outcome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Postgraduate Institute of Medical Education and Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Postgraduate Institute of Medical Education and Research</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Alcoholic liver disease has become one of the foremost causes of chronic liver disease across&#xD;
      the world, and a cause of considerable morbidity and mortality. Alcoholic steatohepatitis is&#xD;
      an entity in this broad spectrum, with severe alcoholic hepatitis transitioning to acute on&#xD;
      chronic liver failure carrying a one month mortality of as high as 20 to 50%.&#xD;
&#xD;
      The current management guidelines for severe alcoholic hepatitis show benefit with prolonged&#xD;
      alcohol abstinence, nutritional support, the use of corticosteroids, pentoxifylline or&#xD;
      N-acetyl cysteine (NAC) and early liver transplantation. However, major studies and&#xD;
      meta-analyses have demonstrated that these interventions, with the exception of early liver&#xD;
      transplantation, do not improve mortality rates to the level of statistical significance.&#xD;
      Owing to the high short term mortality associated with severe alcoholic hepatitis, the&#xD;
      inadequacy of a treatment that could significantly impact this short term mortality, and the&#xD;
      limited applicability of early liver transplantation, a study on newer modalities of&#xD;
      treatment is warranted.&#xD;
&#xD;
      The role that human gut microbiota plays in health and disease is receiving considerable&#xD;
      attention. Targeting intestinal dysbiosis, a phenomenon found to be intricately linked with&#xD;
      the causation of alcoholic hepatitis, could provide insights into novel therapeutic&#xD;
      strategies.&#xD;
&#xD;
      Fecal microbiota transplantation is a novel approach that has gained widespread acceptance in&#xD;
      in the management of recurrent severe Clostridium difficile infection. It's role is also&#xD;
      being studied in other diseases where an association with gut dysbiosis has been found, such&#xD;
      as in inflammatory bowel disease and irritable bowel syndrome. The role of FMT has also been&#xD;
      studied in liver diseases such as non-alcoholic fatty liver disease (NAFLD), liver cirrhosis&#xD;
      and primary sclerosing cholangitis. In this process, a diseased recipient is transferred&#xD;
      fecal material containing the microflora of a healthy individual. It limits the colonization&#xD;
      of pathogens, inducing colonization resistance, affects microbiota composition in the gut, as&#xD;
      well as metabolism in the microbial pathogens. FMT helps alleviate gut dysbiosis and restores&#xD;
      gut microbial diversity.&#xD;
&#xD;
      Our aim is to evaluate the role of FMT on short term survival and improvement in scores of&#xD;
      prognostic significance (CTP, MELD, MELDNa, mDF) in patients with severe alcoholic hepatitis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">January 2019</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">December 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Survival</measure>
    <time_frame>3 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Improvement in CTP (Child Turcotte Pugh Score)</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in MELD score</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in MELDNa score</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in CLIF SOFA score</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in mDF</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in inflammatory markers (IL1b, IL6, TNF α) pre and post FMT,</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Severe Alcoholic Hepatitis</condition>
  <arm_group>
    <arm_group_label>Intervention Arm: Fecal microbiota transplantation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30 grams of stool homogenized with 100 mL of normal saline administered a single time via nasojejunal tube.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Nutritional supplementation, supportive management</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Fecal Microbiota Transplantation</intervention_name>
    <description>30 grams of stool homogenized with 100 mL of normal saline administered a single time via nasojejunal tube.</description>
    <arm_group_label>Intervention Arm: Fecal microbiota transplantation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard of care treatment</intervention_name>
    <description>Nutritional supplementation, supportive management.</description>
    <arm_group_label>Control Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Severe alcoholic hepatitis will be defined as proposed by the American College of&#xD;
             Gastroenterology&#xD;
&#xD;
               1. Rapid development or worsening of jaundice and liver-related complications with&#xD;
                  serum total bilirubin more than 3 milligrams per decilitre.&#xD;
&#xD;
               2. Aspartate aminotransferase and alanine aminotransferase elevated to more than one&#xD;
                  and half times the upper limit of normal, but less than 400 IU per litre, with&#xD;
                  AST to ALT ratio over 1.5.&#xD;
&#xD;
               3. Documentation of persistent heavy alcohol use until 8 weeks before onset of&#xD;
                  symptoms.&#xD;
&#xD;
               4. Alcohol Consumption in female over 40 grams per day for at least 6 months and in&#xD;
                  males over 60 grams per day for at least 6 months.&#xD;
&#xD;
               5. Maddrey's Discriminant Function Score of more than 32 OR&#xD;
&#xD;
               6. A patient of alcoholic hepatitis who will present with grade 1 or 2 of hepatic&#xD;
                  encephalopathy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Intestinal paralysis, lack of bowel sounds, intestinal perforation.&#xD;
&#xD;
          2. Uncontrolled infections.&#xD;
&#xD;
          3. Uncontrolled upper gastrointestinal bleeding.&#xD;
&#xD;
          4. Grade 3,4 hepatic encephalopathy.&#xD;
&#xD;
          5. Hepatic or extrahepatic malignancy.&#xD;
&#xD;
          6. Maddrey's Discriminant Function (mDF) &gt;90 or MELD&gt;30.&#xD;
&#xD;
          7. Autoimmune hepatitis, Wilson's disease, suspected drug induced liver injury.&#xD;
&#xD;
          8. Patients who are aged &gt;60 years&#xD;
&#xD;
          9. WBC count &lt;1000 cells/mm3&#xD;
&#xD;
         10. Pregnancy or nursing.&#xD;
&#xD;
         11. Human Immunodeficiency Virus (HIV), HBV, HCV infection.&#xD;
&#xD;
         12. Patient's unwillingness to participate in the study.&#xD;
&#xD;
         13. Any other condition which, in the opinion of the investigator, would impede compliance&#xD;
             or hinder completion of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Radha K Dhiman, DM</last_name>
    <phone>7087009337</phone>
    <email>rkpsdhiman@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Postgraduate Institute of Medical Education and Research</name>
      <address>
        <city>Chandigarh</city>
        <zip>160012</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Radha K Dhiman, DM</last_name>
      <phone>7087009337</phone>
      <email>rkpsdhiman@hotmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 31, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>January 31, 2019</last_update_submitted>
  <last_update_submitted_qc>January 31, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Postgraduate Institute of Medical Education and Research</investigator_affiliation>
    <investigator_full_name>Radha K Dhiman</investigator_full_name>
    <investigator_title>Professor and Head, Department of Hepatology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Hepatitis, Alcoholic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03827772
org study id: PGIMER Hepatology
nct id: NCT03827772
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Survival
time frame: 3 months
measure: Improvement in CTP (Child Turcotte Pugh Score)
time frame: 3 months
measure: Improvement in MELD score
time frame: 3 months
measure: Improvement in MELDNa score
time frame: 3 months
measure: Improvement in CLIF SOFA score
time frame: 3 months
measure: Improvement in mDF
time frame: 3 months
measure: Changes in inflammatory markers (IL1b, IL6, TNF α) pre and post FMT,
time frame: 3 months
arm group label: Intervention Arm: Fecal microbiota transplantation
arm group type: Experimental
description: 30 grams of stool homogenized with 100 mL of normal saline administered a single time via nasojejunal tube.
arm group label: Control Arm
arm group type: Other
description: Nutritional supplementation, supportive management
intervention type: Other
intervention name: Fecal Microbiota Transplantation
description: 30 grams of stool homogenized with 100 mL of normal saline administered a single time via nasojejunal tube.
arm group label: Intervention Arm: Fecal microbiota transplantation
intervention type: Other
intervention name: Standard of care treatment
description: Nutritional supplementation, supportive management.
arm group label: Control Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Radha K Dhiman, DM
phone: 7087009337
email: rkpsdhiman@hotmail.com
facility: 
status: Recruiting
contact: 
country: India
responsible party type: Principal Investigator
investigator affiliation: Postgraduate Institute of Medical Education and Research
investigator full name: Radha K Dhiman
investigator title: Professor and Head, Department of Hepatology
mesh term: Hepatitis A
mesh term: Hepatitis
mesh term: Hepatitis, Alcoholic
sharing ipd: No