<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/NCT03803540</url>
  </required_header>
  <id_info>
    <org_study_id>FMT-NASH</org_study_id>
    <nct_id>NCT03803540</nct_id>
  </id_info>
  <brief_title>Fecal Microbiota Transplantation for the Treatment of Non-Alcoholic Steatohepatitis</brief_title>
  <acronym>FMT-NASH</acronym>
  <official_title>Fecal Microbiota Transplantation for the Treatment of Non-Alcoholic Steatohepatitis, a Pilot Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Puerta de Hierro University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hospital Universitario Marqués de Valdecilla</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Puerta de Hierro University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Human microbiota is the set of microorganisms that, in a symbiotic way, coexist and develop&#xD;
      in the different surfaces (skin and mucous membranes) of the human body. It is estimated that&#xD;
      it is composed of approximately 10^14 bacteria and other unicellular life forms . The&#xD;
      gastrointestinal (GI) tract is the organ in which the microbiota reaches its greatest&#xD;
      complexity, influencing its metabolic activities in different organs and human systems.&#xD;
&#xD;
      Human microbiota plays a role in multiple homeostatic and physiological functions including&#xD;
      energy and intermediary metabolism, normal immune responses, and even appropriate bowel&#xD;
      development and nervous system functioning. Given its vascular supply, the liver plays&#xD;
      important roles in metabolism and immunological functions. It receives 70% of blood supply&#xD;
      through the portal vein which carries all metabolic products derived from GI microbiota.&#xD;
&#xD;
      Non alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease&#xD;
      in developed countries (with an estimated prevalence around 25 - 40% of adults) and it is&#xD;
      expected that the burden of disease will increase in the near future. This condition can&#xD;
      progress through a spectrum of progressive liver damage to non alcoholic steatohepatitis&#xD;
      (NASH), liver fibrosis, cirrhosis and liver cancer. Around 20-30% of NAFLD patients develop&#xD;
      NASH, with a lower rate progressing further to fibrosis and cirrhosis. Currently, there is no&#xD;
      approved pharmacological or interventional treatment for the management of this so prevalent&#xD;
      disease, apart from changes in lifestyle aiming weight loss.&#xD;
&#xD;
      The aim of the present pilot study is to assess the efficacy and safety of microbiota&#xD;
      manipulation by means of Fecal Microbiota Transplantation in the treatment of patients with&#xD;
      NASH.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">May 1, 2022</start_date>
  <completion_date type="Anticipated">April 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy (Histological resolution of NASH defined as ballooning disappearance with or without persistence of minimal lobulillar inflammation and no progression of fibrosis stage)</measure>
    <time_frame>72 weeks</time_frame>
    <description>Two liver biopsy samples (one pre-FMT and the second 72 weeks after FMT) will be taken. Resolution of NASH is defined as ballooning disappearance with or without persistence of minimal lobulillar inflammation and no progression of fibrosis stage. NAFLD Activity Score is the histological scale that will be used.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety (Appearance of adverse events related with Fecal Microbiota Transplantation)</measure>
    <time_frame>72 weeks</time_frame>
    <description>Appearance of adverse events related with Fecal Microbiota Transplantation will be recorded during 72 weeks follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microbiota composition (Changes in microbiota diversity profile related with Fecal Microbiota Transplantation via 16S rRNA analysis)</measure>
    <time_frame>72 weeks</time_frame>
    <description>Changes in microbiota diversity profile related with Fecal Microbiota Transplantation procedure. 16S rRNA sequencing techniques will be applied on stool samples.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Non-Alcoholic Fatty Liver Disease</condition>
  <condition>Non Alcoholic Steatohepatitis</condition>
  <arm_group>
    <arm_group_label>Fecal Microbiota Transplantation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lean healthy donor frozen fecal microbiota will be administered via duodenal infusion in an upper gastrointestinal endoscopy</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Fecal Microbiota Transplantation</intervention_name>
    <description>Fecal Microbiota Transplantation via duodenal infusion</description>
    <arm_group_label>Fecal Microbiota Transplantation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body Mass Index &gt; 30 Kg / m^2&#xD;
&#xD;
          -  Histological evidence of NASH (by means of hepatic percutaneous biopsy obtained in the&#xD;
             previous six months) defined as at least 1 point in each category of NAFLD Activity&#xD;
             Score with a fibrosis stage between 0 and 3.&#xD;
&#xD;
          -  Global NAFLD Activity Score &gt;= 4 points&#xD;
&#xD;
          -  For patients with fibrosis stage 0 or 1, NAFLD Activity Score should be &gt;= 5 points&#xD;
             and they should have one of the following comorbidities: Metabolic Syndrome, type 2&#xD;
             diabetes mellitus or Homeostasis Model Assessment - Insulin Resistance (HOMA-IR) &gt; 6.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients unable or unwilling to give the informed consent&#xD;
&#xD;
          -  Patients actively participating in another clinical trial or investigational protocol&#xD;
&#xD;
          -  Cirrhosis of the liver: Transient elastography &gt; 20 kilopascal or histological&#xD;
             evidence of it (grade 4 fibrosis)&#xD;
&#xD;
          -  Alcoholic consumption greater than 14 g / week in women or 21 g / week in men&#xD;
&#xD;
          -  Any significant hepatic comorbidity: chronic active viral hepatitis, cholestatic&#xD;
             disease, hemochromatosis or Wilson disease&#xD;
&#xD;
          -  HIV infection&#xD;
&#xD;
          -  Liver transplantation&#xD;
&#xD;
          -  Hepatocellular carcinoma&#xD;
&#xD;
          -  Women during pregnancy or breastfeeding&#xD;
&#xD;
          -  Portal thrombosis&#xD;
&#xD;
          -  Non-cirrhotic portal hypertension&#xD;
&#xD;
          -  Gastroesophageal varices&#xD;
&#xD;
          -  Previous gastrointestinal tract major surgery (excluding appendectomy and&#xD;
             cholecystectomy)&#xD;
&#xD;
          -  Previous Fecal Microbiota Transplantation&#xD;
&#xD;
          -  Chronic significant kidney or heart disease&#xD;
&#xD;
          -  Life expectancy lower than two years&#xD;
&#xD;
          -  Chronic use of steatogenic drugs&#xD;
&#xD;
          -  Chronic use of immunosuppressants&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Puerta de Hierro University Hospital</name>
      <address>
        <city>Majadahonda</city>
        <state>Madrid</state>
        <zip>28222</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>April 13, 2022</last_update_submitted>
  <last_update_submitted_qc>April 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Puerta de Hierro University Hospital</investigator_affiliation>
    <investigator_full_name>Jose Luis Calleja</investigator_full_name>
    <investigator_title>Head of the department of Gastroenterology and Hepatology</investigator_title>
  </responsible_party>
  <keyword>Non-Alcoholic Fatty Liver Disease</keyword>
  <keyword>Non Alcoholic Steatohepatitis</keyword>
  <keyword>NAFLD</keyword>
  <keyword>NASH</keyword>
  <keyword>Fecal Microbiota Transplantation</keyword>
  <keyword>FMT</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</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/NCT03803540
org study id: FMT-NASH
nct id: NCT03803540
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Human microbiota is the set of microorganisms that, in a symbiotic way, coexist and develop
      in the different surfaces (skin and mucous membranes) of the human body. It is estimated that
      it is composed of approximately 10^14 bacteria and other unicellular life forms . The
      gastrointestinal (GI) tract is the organ in which the microbiota reaches its greatest
      complexity, influencing its metabolic activities in different organs and human systems.

      Human microbiota plays a role in multiple homeostatic and physiological functions including
      energy and intermediary metabolism, normal immune responses, and even appropriate bowel
      development and nervous system functioning. Given its vascular supply, the liver plays
      important roles in metabolism and immunological functions. It receives 70% of blood supply
      through the portal vein which carries all metabolic products derived from GI microbiota.

      Non alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease
      in developed countries (with an estimated prevalence around 25 - 40% of adults) and it is
      expected that the burden of disease will increase in the near future. This condition can
      progress through a spectrum of progressive liver damage to non alcoholic steatohepatitis
      (NASH), liver fibrosis, cirrhosis and liver cancer. Around 20-30% of NAFLD patients develop
      NASH, with a lower rate progressing further to fibrosis and cirrhosis. Currently, there is no
      approved pharmacological or interventional treatment for the management of this so prevalent
      disease, apart from changes in lifestyle aiming weight loss.

      The aim of the present pilot study is to assess the efficacy and safety of microbiota
      manipulation by means of Fecal Microbiota Transplantation in the treatment of patients with
      NASH.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Efficacy (Histological resolution of NASH defined as ballooning disappearance with or without persistence of minimal lobulillar inflammation and no progression of fibrosis stage)
time frame: 72 weeks
description: Two liver biopsy samples (one pre-FMT and the second 72 weeks after FMT) will be taken. Resolution of NASH is defined as ballooning disappearance with or without persistence of minimal lobulillar inflammation and no progression of fibrosis stage. NAFLD Activity Score is the histological scale that will be used.
measure: Safety (Appearance of adverse events related with Fecal Microbiota Transplantation)
time frame: 72 weeks
description: Appearance of adverse events related with Fecal Microbiota Transplantation will be recorded during 72 weeks follow-up.
measure: Microbiota composition (Changes in microbiota diversity profile related with Fecal Microbiota Transplantation via 16S rRNA analysis)
time frame: 72 weeks
description: Changes in microbiota diversity profile related with Fecal Microbiota Transplantation procedure. 16S rRNA sequencing techniques will be applied on stool samples.
arm group label: Fecal Microbiota Transplantation
arm group type: Experimental
description: Lean healthy donor frozen fecal microbiota will be administered via duodenal infusion in an upper gastrointestinal endoscopy
intervention type: Other
intervention name: Fecal Microbiota Transplantation
description: Fecal Microbiota Transplantation via duodenal infusion
arm group label: Fecal Microbiota Transplantation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Puerta de Hierro University Hospital
investigator full name: Jose Luis Calleja
investigator title: Head of the department of Gastroenterology and Hepatology
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
sharing ipd: No