xml: <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/NCT06024681</url>
    </required_header>
    <id_info>
      <org_study_id>ICL_21SM6787</org_study_id>
      <secondary_id>296522</secondary_id>
      <secondary_id>21/LO/0454</secondary_id>
      <nct_id>NCT06024681</nct_id>
    </id_info>
    <brief_title>Impact of FMT on the Phenome in Patients With NAFLD and Fibrosis</brief_title>
    <official_title>Investigating the Impact of Faecal Microbiota Transplant on the Clinical Phenome of Patients With Non-alcoholic Fatty Liver Disease and Fibrosis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Imperial College London</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>King's College London</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Imperial College London</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>
        The goal of this pilot experimental medicine interventional study is to explore the degree of&#xD;
        transferability of the gut microbiome and associated metabolomic changes in patients with&#xD;
        non-alcoholic fatty liver disease (NAFLD) and fibrosis who receive faecal microbiota&#xD;
        transplant (FMT). The main questions is aims to answer is:&#xD;
  &#xD;
          -  To what extent is the gut microbiome transferable from donor to recipient in patients&#xD;
             with NAFLD with fibrosis who receive FMT?&#xD;
  &#xD;
          -  What are the dynamics of how the gut microbiome changes over time in these patients?&#xD;
  &#xD;
          -  To what degree does the recipient metabolome change in association with this?&#xD;
  &#xD;
        Participants will receive up to three capsulised FMT preparations prepared from a donor&#xD;
        selected rationally based upon their metabolomic characteristics. They will be asked to&#xD;
        attend for serial clinical assessments (including FibroScan and MRE/ MRI-PDFF), and will also&#xD;
        be asked to provide serial blood, urine and stool samples for assessment of microbiome and&#xD;
        metabolome profiling.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 20, 2021</start_date>
    <completion_date type="Anticipated">May 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">September 29, 2023</primary_completion_date>
    <phase>N/A</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>
      <intervention_model_description>Human participants with NAFLD and fibrosis</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in faecal microbiome composition</measure>
      <time_frame>24 weeks after initial FMT</time_frame>
      <description>Using 16S rRNA gene sequencing and shotgun metagenomic sequencing</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in gut microbial metabolite composition</measure>
      <time_frame>24 weeks after initial FMT</time_frame>
      <description>Using 1H-NMR and mass spectrometry</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Changes in liver fat on MRI</measure>
      <time_frame>16 weeks after initial FMT</time_frame>
      <description>Using MRI-PDFF</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in liver fat on FibroScan</measure>
      <time_frame>16 weeks after initial FMT</time_frame>
      <description>Using CAP</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in liver stiffness on MRI</measure>
      <time_frame>16 weeks after initial FMT</time_frame>
      <description>Using MRE</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in liver stiffness on FibroScan</measure>
      <time_frame>16 weeks after initial FMT</time_frame>
      <description>Using transient elastography</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in HbA1c</measure>
      <time_frame>24 weeks after initial FMT</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in insulin resistance</measure>
      <time_frame>24 weeks after initial FMT</time_frame>
      <description>Combining fasting glucose and insulin levels to generate HOMA-IR</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in BMI</measure>
      <time_frame>24 weeks after initial FMT</time_frame>
      <description>Through combination of measurement of weight in kilogram and height in metres, reporting BMI in kg/m^2</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in lipid metabolism</measure>
      <time_frame>24 weeks after initial FMT</time_frame>
      <description>Serum lipid profile</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">16</enrollment>
    <condition>Non-Alcoholic Fatty Liver Disease</condition>
    <condition>Fecal Microbiota Transplantation</condition>
    <arm_group>
      <arm_group_label>NAFLD patients</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receiving capsulised FMT</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Faecal microbiota transplant</intervention_name>
      <description>Capsulised faecal microbiota transplant prepared from rationally selected donor, based upon donor metabolomic charateristics</description>
      <arm_group_label>NAFLD patients</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. 18-75 years of age.&#xD;
  &#xD;
            2. Previously-diagnosed NAFLD, with predicted fibrosis based upon non-invasive assessment&#xD;
               with FibroScan (i.e. liver stiffness measurement (LSM) &gt; 8kPa).&#xD;
  &#xD;
            3. Raised liver ALT (&gt; 30IU/l for men, &gt; 19IU/l for women) or AST (&gt; 37IU/l for men, &gt;&#xD;
               31IU/l for women) with negative non-invasive liver screen (including negative screen&#xD;
               for viral hepatitis, autoimmune liver disease and metabolic liver disease, and normal&#xD;
               echocardiogram within two years in the scenario where congestive hepatopathy may be&#xD;
               considered).&#xD;
  &#xD;
            4. Able to consent for themselves in English.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Severe or life-threatening food allergy.&#xD;
  &#xD;
            2. Pregnant or lactating women; or women trying to conceive.&#xD;
  &#xD;
            3. Patients with suspected or confirmed cirrhosis (as assessed by clinical, radiological&#xD;
               or histological criteria).&#xD;
  &#xD;
            4. Use of particular medications, including:&#xD;
  &#xD;
                 1. Systemic antibiotics within the six weeks prior to study enrolment.&#xD;
  &#xD;
                 2. Immunosuppression that may influence risks related to FMT (including - but not&#xD;
                    limited to: use of corticosteroids within eight weeks of intervention; use of&#xD;
                    cytotoxic chemotherapy; use of azathioprine, tacrolimus, mycophenolate mofetil&#xD;
                    and/or immunosuppressive biologic therapy, e.g. infliximab).&#xD;
  &#xD;
                 3. Use of GLP-1 agonists.&#xD;
  &#xD;
            5. Patients not expected to survive the duration of the study's follow-up (six months).&#xD;
  &#xD;
            6. Swallowing difficulties that may preclude safe use of FMT capsules, including&#xD;
               oral-motor dyscoordination.&#xD;
  &#xD;
            7. Alcohol consumption &gt; 20g/ day.&#xD;
  &#xD;
            8. Any active cancer (including treatment within the past six months).&#xD;
  &#xD;
            9. Active infection at the point of recruitment, including COVID-19 infection.&#xD;
  &#xD;
           10. Prior receipt of a liver transplant.&#xD;
  &#xD;
           11. BMI &lt; 23 in Asian potential participants and BMI &lt; 25 in Caucasians.&#xD;
  &#xD;
           12. Advanced chronic kidney disease (eGFR &lt; 30 ml/min).&#xD;
  &#xD;
           13. Chronic intestinal disease, including coeliac disease, cystic fibrosis, inflammatory&#xD;
               bowel disease, irritable bowel syndrome, and chronic diarrhoea.&#xD;
  &#xD;
           14. Prior bariatric surgery.&#xD;
  &#xD;
           15. Patients unable to undergo MRI scans (e.g. due to the individual having metallic&#xD;
               implants).&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Pinelopi Manousou, MD PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Imperial College London</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Benjamin H Mullish, MB Chir PhD</last_name>
      <phone>+442033126454</phone>
      <email>b.mullish@imperial.ac.uk</email>
    </overall_contact>
    <location>
      <facility>
        <name>Division of Digestive Diseases/ Liver Unit, St Mary's Hospital Campus, Imperial College London</name>
        <address>
          <city>London</city>
          <zip>W2 1NY</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Claire Parsonage</last_name>
      </contact>
      <investigator>
        <last_name>Mark R Thursz, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 23, 2023</study_first_submitted>
    <study_first_submitted_qc>August 29, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 6, 2023</study_first_posted>
    <last_update_submitted>August 29, 2023</last_update_submitted>
    <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>NAFLD</keyword>
    <keyword>Gut microbiome</keyword>
    <keyword>Metabolomics</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>
      <ipd_description>Only anonymised microbiome and metabolome data will be shared with other researchers via open access repositories</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06024681
  org study id: ICL_21SM6787
  secondary id: 296522
  secondary id: 21/LO/0454
  nct id: NCT06024681
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this pilot experimental medicine interventional study is to explore the degree of
        transferability of the gut microbiome and associated metabolomic changes in patients with
        non-alcoholic fatty liver disease (NAFLD) and fibrosis who receive faecal microbiota
        transplant (FMT). The main questions is aims to answer is:
  
          -  To what extent is the gut microbiome transferable from donor to recipient in patients
             with NAFLD with fibrosis who receive FMT?
  
          -  What are the dynamics of how the gut microbiome changes over time in these patients?
  
          -  To what degree does the recipient metabolome change in association with this?
  
        Participants will receive up to three capsulised FMT preparations prepared from a donor
        selected rationally based upon their metabolomic characteristics. They will be asked to
        attend for serial clinical assessments (including FibroScan and MRE/ MRI-PDFF), and will also
        be asked to provide serial blood, urine and stool samples for assessment of microbiome and
        metabolome profiling.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Human participants with NAFLD and fibrosis
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: Change in faecal microbiome composition
  time frame: 24 weeks after initial FMT
  description: Using 16S rRNA gene sequencing and shotgun metagenomic sequencing
  measure: Change in gut microbial metabolite composition
  time frame: 24 weeks after initial FMT
  description: Using 1H-NMR and mass spectrometry
  measure: Changes in liver fat on MRI
  time frame: 16 weeks after initial FMT
  description: Using MRI-PDFF
  measure: Changes in liver fat on FibroScan
  time frame: 16 weeks after initial FMT
  description: Using CAP
  measure: Changes in liver stiffness on MRI
  time frame: 16 weeks after initial FMT
  description: Using MRE
  measure: Changes in liver stiffness on FibroScan
  time frame: 16 weeks after initial FMT
  description: Using transient elastography
  measure: Changes in HbA1c
  time frame: 24 weeks after initial FMT
  measure: Changes in insulin resistance
  time frame: 24 weeks after initial FMT
  description: Combining fasting glucose and insulin levels to generate HOMA-IR
  measure: Changes in BMI
  time frame: 24 weeks after initial FMT
  description: Through combination of measurement of weight in kilogram and height in metres, reporting BMI in kg/m^2
  measure: Changes in lipid metabolism
  time frame: 24 weeks after initial FMT
  description: Serum lipid profile
  arm group label: NAFLD patients
  arm group type: Experimental
  description: Patients receiving capsulised FMT
  intervention type: Other
  intervention name: Faecal microbiota transplant
  description: Capsulised faecal microbiota transplant prepared from rationally selected donor, based upon donor metabolomic charateristics
  arm group label: NAFLD patients
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Pinelopi Manousou, MD PhD
  role: Principal Investigator
  affiliation: Imperial College London
  last name: Benjamin H Mullish, MB Chir PhD
  phone: +442033126454
  email: b.mullish@imperial.ac.uk
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: United Kingdom
  responsible party type: Sponsor
  mesh term: Liver Diseases
  mesh term: Fatty Liver
  mesh term: Non-alcoholic Fatty Liver Disease
  sharing ipd: No
  ipd description: Only anonymised microbiome and metabolome data will be shared with other researchers via open access repositories