<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/NCT03802890</url>
  </required_header>
  <id_info>
    <org_study_id>QIB01/2018</org_study_id>
    <nct_id>NCT03802890</nct_id>
  </id_info>
  <brief_title>Microbial Dysbiosis in Rheumatoid Arthritis</brief_title>
  <acronym>MyRA</acronym>
  <official_title>Microbial Dysbiosis in the Pathogenesis of Rheumatoid Arthritis: Using Metagenomics to Predict Methotrexate Efficacy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Quadram Institute Bioscience</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Action Arthritis</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of East Anglia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Norfolk and Norwich University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Quadram Institute Bioscience</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 MyRA study will primarily investigate whether there are associations between the&#xD;
      structure and function of the gut microbiome and response to methotrexate in early rheumatoid&#xD;
      arthritis patients. The microbiome will be characterised via shotgun metagenomic sequencing&#xD;
      of microbial DNA present in stool samples taken during the participant's first 6 months of&#xD;
      taking methotrexate.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Methotrexate is often the first drug of choice for patients with early rheumatoid arthritis&#xD;
      (RA), but its efficacy is highly variable and it can lead to severe side effects. There are&#xD;
      currently no reliable predictors of methotrexate efficacy for people with early RA.&#xD;
&#xD;
      Microbial dysbiosis (an imbalanced microbiome) has recently been implicated in RA, with&#xD;
      associations between specific microbes and RA biomarkers or disease activity. Gut microbes&#xD;
      have extensive capabilities in terms of xenobiotic (e.g. drug) metabolism. Several gut&#xD;
      microbes are able to alter the drug methotrexate in vitro, and it is possible this could&#xD;
      effect drug efficacy in vivo. Alternatively methotrexate efficacy could be affected by&#xD;
      baseline microbial composition or alterations to microbial composition over the course of&#xD;
      treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date type="Actual">February 1, 2019</start_date>
  <completion_date type="Anticipated">July 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">April 30, 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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in DAS28-CRP score</measure>
    <time_frame>0-6 months</time_frame>
    <description>Disease Activity Score using 28 joints and C-reactive Protein</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in SDAI score</measure>
    <time_frame>0-6 months</time_frame>
    <description>Simplified Disease Activity Index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of CRP in blood</measure>
    <time_frame>0-6 months</time_frame>
    <description>C-reactive Protein (an inflammatory biomarker)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ESR value (blood)</measure>
    <time_frame>0-6 months</time_frame>
    <description>Erythrocyte Sedimentation Rate (an inflammatory biomarker)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of anti-CCP in blood</measure>
    <time_frame>0-6 months</time_frame>
    <description>Anti-Cyclic Citrullinated peptide (disease-specific antibody)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of RF in blood</measure>
    <time_frame>0-6 months</time_frame>
    <description>Rheumatoid Factor (disease-specific antibody)</description>
  </secondary_outcome>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      -  faecal samples&#xD;
&#xD;
        -  blood samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Early rheumatoid arthritis commencing methotrexate monotherapy&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18-65 years of age&#xD;
&#xD;
          -  RA diagnosis based on ACR 2010 classification criteria with symptoms starting within&#xD;
             the last 2 years&#xD;
&#xD;
          -  Referred by GP to the Early Arthritis Clinic at the Norfolk and Norwich University&#xD;
             Hospitals NHS trust&#xD;
&#xD;
          -  Commencing methotrexate monotherapy for the first time&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Initially commencing combination therapy (prior to first stool sample) rather than&#xD;
             methotrexate monotherapy i.e. MTX combined with another DMARD or prednisolone&#xD;
&#xD;
          -  Commencement of MTX therapy prior to first stool sample or cessation of MTX therapy at&#xD;
             any point during the study&#xD;
&#xD;
          -  History of psoriasis&#xD;
&#xD;
          -  Those currently suffering from, or have ever suffered from, any diagnosed&#xD;
             gastrointestinal disease, gastrointestinal disorders including regular diarrhoea and&#xD;
             constipation (excluding hiatus hernia unless symptomatic) and/or have undergone&#xD;
             gastrointestinal surgery.&#xD;
&#xD;
          -  Those regularly (3+ times/week) taking self-prescribed over the counter medications&#xD;
             for digestive/gastrointestinal conditions&#xD;
&#xD;
          -  Use of laxatives within 7 days prior to sampling unless these have been used on a&#xD;
             regular basis (3+ times/week) for more than one month prior to the study and will&#xD;
             continue to be used throughout the study period&#xD;
&#xD;
          -  The use of over-the-counter medications or food/drinks containing pre and/or&#xD;
             probiotics within 7 days prior to sampling, unless these have been used on a regular&#xD;
             basis (3+ times/week) for more than one month prior to the study and will continue to&#xD;
             be used throughout the study period&#xD;
&#xD;
          -  Significant alteration of the participant's normal diet at any point during the study&#xD;
             (e.g. adoption of the 5:2 fasting diet)&#xD;
&#xD;
          -  Regular (3+ times/week) or recent (within 3 months) use of colonic irrigation or other&#xD;
             bowel cleansing techniques&#xD;
&#xD;
          -  Recently returned to the UK following a period abroad, and who have suffered gastric&#xD;
             symptoms during the period abroad or on return to the UK. These will be assessed on an&#xD;
             individual basis&#xD;
&#xD;
          -  Currently taking or finished a course of antibiotics within the last 3 months&#xD;
&#xD;
          -  Currently pregnant or lactating&#xD;
&#xD;
          -  Living with or related to any member of the Study Team&#xD;
&#xD;
          -  Those who have limited or no understanding of spoken and written English&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Simon Carding, Prof</last_name>
    <role>Study Chair</role>
    <affiliation>Quadram Institute Bioscience</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Norfolk and Norwich University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Norwich</city>
        <state>Norfolk</state>
        <zip>NR4 7UY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>January 10, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>June 17, 2020</last_update_submitted>
  <last_update_submitted_qc>June 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>microbial dysbiosis</keyword>
  <keyword>rheumatoid arthritis</keyword>
  <keyword>dietary factors</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>Dysbiosis</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 8, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/90/NCT03802890/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03802890
org study id: QIB01/2018
nct id: NCT03802890
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The MyRA study will primarily investigate whether there are associations between the
      structure and function of the gut microbiome and response to methotrexate in early rheumatoid
      arthritis patients. The microbiome will be characterised via shotgun metagenomic sequencing
      of microbial DNA present in stool samples taken during the participant's first 6 months of
      taking methotrexate.
Methotrexate is often the first drug of choice for patients with early rheumatoid arthritis
      (RA), but its efficacy is highly variable and it can lead to severe side effects. There are
      currently no reliable predictors of methotrexate efficacy for people with early RA.

      Microbial dysbiosis (an imbalanced microbiome) has recently been implicated in RA, with
      associations between specific microbes and RA biomarkers or disease activity. Gut microbes
      have extensive capabilities in terms of xenobiotic (e.g. drug) metabolism. Several gut
      microbes are able to alter the drug methotrexate in vitro, and it is possible this could
      effect drug efficacy in vivo. Alternatively methotrexate efficacy could be affected by
      baseline microbial composition or alterations to microbial composition over the course of
      treatment.
observational model: Cohort
time perspective: Prospective
measure: Change in DAS28-CRP score
time frame: 0-6 months
description: Disease Activity Score using 28 joints and C-reactive Protein
measure: Change in SDAI score
time frame: 0-6 months
description: Simplified Disease Activity Index
measure: Concentration of CRP in blood
time frame: 0-6 months
description: C-reactive Protein (an inflammatory biomarker)
measure: ESR value (blood)
time frame: 0-6 months
description: Erythrocyte Sedimentation Rate (an inflammatory biomarker)
measure: Concentration of anti-CCP in blood
time frame: 0-6 months
description: Anti-Cyclic Citrullinated peptide (disease-specific antibody)
measure: Concentration of RF in blood
time frame: 0-6 months
description: Rheumatoid Factor (disease-specific antibody)
-  faecal samples

        -  blood samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Simon Carding, Prof
role: Study Chair
affiliation: Quadram Institute Bioscience
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Dysbiosis
provided document: 