<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/NCT04493762</url>
  </required_header>
  <id_info>
    <org_study_id>UW19-839</org_study_id>
    <nct_id>NCT04493762</nct_id>
  </id_info>
  <brief_title>Liver Fibrosis and Gut Microbiota in Patients With Psoriasis Vulgaris and Rheumatoid Arthritis on Methotrexate</brief_title>
  <official_title>A Comparison Study of Liver Fibrosis and Its Association With Gut Microbiota in Patients With Psoriasis Vulgaris and Rheumatoid Arthritis on Methotrexate</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Hong Kong</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>
      While methotrexate (MTX) remains a treatment of choice for patients with rheumatoid arthritis&#xD;
      (RA), psoriasis (PsO) and psoriatic arthritis (PsA), long-term MTX use has been shown to be&#xD;
      associated with liver fibrosis and cirrhosis in these patients. In addition, gut dysbiosis&#xD;
      has been found to be associated with liver fibrosis and cirrhosis via the gut-liver axis,&#xD;
      underscoring the potential role of gut microbiota and bacterial translocation in the&#xD;
      pathogenesis of chronic liver diseases in these patients.&#xD;
&#xD;
      In this study, we aim to assess the prevalence of advanced liver fibrosis or cirrhosis among&#xD;
      these patients on MTX treatment compared to those without, using transient elastography. We&#xD;
      also aim to identify the possible risk factor(s) for advanced liver fibrosis or cirrhosis&#xD;
      among them. Further, we aim to characterize the difference in fecal microbiota patterns among&#xD;
      these three groups of patients.&#xD;
&#xD;
      Using a cross-sectional, prospective cohort design, this study will enroll approximately 600&#xD;
      eligible patients, including 300 patients with PsO/PsA and 300 patients with RA, to examine&#xD;
      the following hypotheses:&#xD;
&#xD;
        1. Patients on higher cumulative dose of MTX will have higher prevalence of advanced liver&#xD;
           fibrosis or cirrhosis compared to those on lower cumulative dose of MTX;&#xD;
&#xD;
        2. Patients with MTX use will have higher prevalence of advanced liver fibrosis or&#xD;
           cirrhosis compared to those without MTX use;&#xD;
&#xD;
        3. The fecal microbiota composition will be different between patients with and without MTX&#xD;
           treatment; and&#xD;
&#xD;
        4. The fecal microbiota composition will be different between patients with and without&#xD;
           advanced fibrosis/cirrhosis while on MTX treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">August 13, 2020</start_date>
  <completion_date type="Anticipated">December 11, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 12, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The number of patients with advanced liver fibrosis or cirrhosis</measure>
    <time_frame>At the time of the assessment procedure</time_frame>
    <description>We will measure the number of patients with significant fibrosis (defined as having liver stiffness ≥ 7.5 kPa in transient elastography), and among those who undergo biopsy, the number of patients whose biopsy specimen is of Roenigk grades 3b or 4</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The type and abundance of fecal microbiota patterns</measure>
    <time_frame>At the time of the assessment procedure</time_frame>
    <description>We will measure the type and abundance of various bacteria/viruses in specimens; alpha diversity within a specimen and beta diversity between groups of specimen; specific taxa that differ significantly between groups; and metabolic profiles and functional pathways associated with change in gut microbiota</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The risk factors of liver fibrosis</measure>
    <time_frame>At the time of the assessment procedure</time_frame>
    <description>Risk factors to be examined will include demographic variables such as age and gender, cumulative dose of MTX, gut dysbiosis, duration of disease, co-morbidities, hepatic steatosis, liver stiffness, and other potential factors</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">600</enrollment>
  <condition>Psoriasis Vulgaris</condition>
  <condition>Rheumatoid Arthritis</condition>
  <condition>Fibrosis, Liver</condition>
  <arm_group>
    <arm_group_label>PSO/PSA</arm_group_label>
    <description>Patients diagnosed with psoriasis or psoriatic arthritis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RA</arm_group_label>
    <description>Patients diagnosed with rheumatoid arthritis</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood (serum and plasma) and stool samples collected for this study will be saved for 3 years&#xD;
      and stored at - 80 degree Celsius in the laboratory in Hong Kong for biomarker analyses.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        All patients who have regular follow up in Dermatology/ Rheumatology clinics of Queen Mary&#xD;
        Hospital, with a diagnosis of PsO/PsA and/or RA will be identified and screened for&#xD;
        eligibility.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age between 18 to 85 years&#xD;
&#xD;
          -  Have regular follow up in Dermatology/ Rheumatology clinics of Queen Mary Hospital&#xD;
&#xD;
          -  Diagnosed with PsO/PsA or RA&#xD;
&#xD;
          -  Chinese ethnicity&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age below 18 years or above 85 years&#xD;
&#xD;
          -  Known decompensated cirrhosis&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Unstable medical illness or active infection&#xD;
&#xD;
          -  Unable to provide written consent&#xD;
&#xD;
          -  Unable to adhere to the protocol&#xD;
&#xD;
          -  Unable to read and/or write Chinese language&#xD;
&#xD;
          -  On anticoagulant/ antiplatelet treatment&#xD;
&#xD;
          -  Abnormal platelet count &lt;150&#xD;
&#xD;
          -  Known disease/condition with prolonged INR/bleeding tendency&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sze-Man Wong, MSc, MRCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>Queen Mary Hospital, Hong Kong</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sze-Man Wong, MSc, MRCP</last_name>
    <phone>+852 22555154</phone>
    <email>wongsm11@ha.org.hk</email>
  </overall_contact>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>July 27, 2020</last_update_submitted>
  <last_update_submitted_qc>July 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Queen Mary Hospital, Hong Kong</investigator_affiliation>
    <investigator_full_name>Dr. Sze-Man Wong</investigator_full_name>
    <investigator_title>Associate Consultant</investigator_title>
  </responsible_party>
  <keyword>Methotrexate</keyword>
  <keyword>Microbiota</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</mesh_term>
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Psoriasis</mesh_term>
    <mesh_term>Fibrosis</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/NCT04493762
org study id: UW19-839
nct id: NCT04493762
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
While methotrexate (MTX) remains a treatment of choice for patients with rheumatoid arthritis
      (RA), psoriasis (PsO) and psoriatic arthritis (PsA), long-term MTX use has been shown to be
      associated with liver fibrosis and cirrhosis in these patients. In addition, gut dysbiosis
      has been found to be associated with liver fibrosis and cirrhosis via the gut-liver axis,
      underscoring the potential role of gut microbiota and bacterial translocation in the
      pathogenesis of chronic liver diseases in these patients.

      In this study, we aim to assess the prevalence of advanced liver fibrosis or cirrhosis among
      these patients on MTX treatment compared to those without, using transient elastography. We
      also aim to identify the possible risk factor(s) for advanced liver fibrosis or cirrhosis
      among them. Further, we aim to characterize the difference in fecal microbiota patterns among
      these three groups of patients.

      Using a cross-sectional, prospective cohort design, this study will enroll approximately 600
      eligible patients, including 300 patients with PsO/PsA and 300 patients with RA, to examine
      the following hypotheses:

        1. Patients on higher cumulative dose of MTX will have higher prevalence of advanced liver
           fibrosis or cirrhosis compared to those on lower cumulative dose of MTX;

        2. Patients with MTX use will have higher prevalence of advanced liver fibrosis or
           cirrhosis compared to those without MTX use;

        3. The fecal microbiota composition will be different between patients with and without MTX
           treatment; and

        4. The fecal microbiota composition will be different between patients with and without
           advanced fibrosis/cirrhosis while on MTX treatment.
observational model: Cohort
time perspective: Cross-Sectional
measure: The number of patients with advanced liver fibrosis or cirrhosis
time frame: At the time of the assessment procedure
description: We will measure the number of patients with significant fibrosis (defined as having liver stiffness ≥ 7.5 kPa in transient elastography), and among those who undergo biopsy, the number of patients whose biopsy specimen is of Roenigk grades 3b or 4
measure: The type and abundance of fecal microbiota patterns
time frame: At the time of the assessment procedure
description: We will measure the type and abundance of various bacteria/viruses in specimens; alpha diversity within a specimen and beta diversity between groups of specimen; specific taxa that differ significantly between groups; and metabolic profiles and functional pathways associated with change in gut microbiota
measure: The risk factors of liver fibrosis
time frame: At the time of the assessment procedure
description: Risk factors to be examined will include demographic variables such as age and gender, cumulative dose of MTX, gut dysbiosis, duration of disease, co-morbidities, hepatic steatosis, liver stiffness, and other potential factors
arm group label: PSO/PSA
description: Patients diagnosed with psoriasis or psoriatic arthritis
arm group label: RA
description: Patients diagnosed with rheumatoid arthritis
Blood (serum and plasma) and stool samples collected for this study will be saved for 3 years
      and stored at - 80 degree Celsius in the laboratory in Hong Kong for biomarker analyses.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Sze-Man Wong, MSc, MRCP
role: Principal Investigator
affiliation: Queen Mary Hospital, Hong Kong
last name: Sze-Man Wong, MSc, MRCP
phone: +852 22555154
email: wongsm11@ha.org.hk
responsible party type: Principal Investigator
investigator affiliation: Queen Mary Hospital, Hong Kong
investigator full name: Dr. Sze-Man Wong
investigator title: Associate Consultant
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Liver Cirrhosis
mesh term: Psoriasis
mesh term: Fibrosis
sharing ipd: No