<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/NCT02219347</url>
  </required_header>
  <id_info>
    <org_study_id>NUTH7100</org_study_id>
    <nct_id>NCT02219347</nct_id>
  </id_info>
  <brief_title>Biomarkers of Remission in Rheumatoid Arthritis (BioRRA)</brief_title>
  <acronym>BioRRA</acronym>
  <official_title>Biomarkers of Remission in Rheumatoid Arthritis (BioRRA)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Newcastle-upon-Tyne Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Newcastle University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Wellcome Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Newcastle-upon-Tyne Hospitals NHS Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rheumatoid arthritis is a common condition affecting approximately 1% of the United Kingdom&#xD;
      population; it is an autoimmune disease where the body's natural defences (the immune system)&#xD;
      attack the body itself resulting, most notably, in joint damage and arthritis. To help&#xD;
      prevent this, patients with rheumatoid arthritis need to take disease-modifying&#xD;
      anti-rheumatic drugs (DMARDs). As rheumatoid arthritis is a life-long condition, these drug&#xD;
      treatments are prescribed as long-term medications taken for many years.&#xD;
&#xD;
      With successful drug treatment, many patients are able to achieve an excellent control of&#xD;
      their disease and their arthritis can go in to remission. At present, there are no markers&#xD;
      which can reliably predict which of these patients can reduce their drug treatment, and hence&#xD;
      benefit from a lower risk of side effects and inconvenience, without an increase in their&#xD;
      arthritis activity.&#xD;
&#xD;
      We invite patients with stable rheumatoid arthritis to participate in this study conducted by&#xD;
      Newcastle upon Tyne Hospitals NHS Foundation Trust in collaboration with Newcastle University&#xD;
      and funded by the Wellcome Trust. Patients whose arthritis is confirmed as being in remission&#xD;
      will be able to stop their DMARD medication and be monitored for a period of 6 months.&#xD;
      Patients whose arthritis activity increases during this time will be able to restart their&#xD;
      DMARD medication, whereas those patients whose arthritis remains in remission will be able to&#xD;
      stay off DMARD medication.&#xD;
&#xD;
      The main aim of this study is to identify clinical, ultrasound and blood markers that can&#xD;
      predict which patients will remain in remission after stopping DMARD medication. If&#xD;
      identified, these markers could be a useful guide to doctors and patients in the future when&#xD;
      deciding whether to stop DMARD therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2014</start_date>
  <completion_date type="Actual">August 2017</completion_date>
  <primary_completion_date type="Actual">August 2017</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time-to-flare of arthritis activity following DMARD cessation</measure>
    <time_frame>From recruitment, assessed up to 6 months</time_frame>
    <description>Flare of arthritis activity defined as Disease Activity Score in 28 Joints C-Reactive Protein (DAS28-CRP) score greater than or equal to 2.4</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical biomarkers predictive of DMARD-free remission</measure>
    <time_frame>At recruitment</time_frame>
    <description>Baseline clinical factors predictive of time-to-flare of arthritis activity following DMARD cessation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ultrasound biomarkers of DMARD-free remission</measure>
    <time_frame>At recruitment</time_frame>
    <description>Baseline musculoskeletal ultrasound biomarkers predictive of time-to-flare of arthritis activity following DMARD cessation, including presence or absence of greyscale synovitis/tenosynovitis and erosions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genetic biomarkers of DMARD-free remission</measure>
    <time_frame>At recruitment</time_frame>
    <description>Baseline signature of differential gene expression in peripheral CD4+ T cells predictive of DMARD-free remission at 6 months following DMARD cessation, as measured using RNA sequencing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine biomarkers of DMARD-free remission</measure>
    <time_frame>At recruitment</time_frame>
    <description>Baseline signature of differential cytokine levels in peripheral blood predictive of time-to-flare of arthritis activity, as measured using a multiplex cytokine assay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rheumatoid arthritis disease activity</measure>
    <time_frame>At recruitment and at 1 month, 3 months and 6 months following DMARD cessation</time_frame>
    <description>Measured by Disease Activity Score in 28 joints (DAS28-CRP) score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical disability</measure>
    <time_frame>At baseline and at 6 months following DMARD cessation</time_frame>
    <description>Measured by Health Assessment Questionnaire Disability Index (HAQ-DI) questionnaire</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">74</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>DMARD cessation</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All patients recruited to the study who have a Disease Activity in 28 Joints C-Reactive Protein (DAS28-CRP) score of &lt; 2.4 and who do not have power Doppler synovitis on a 7-joint musculoskeletal ultrasound scan will stop their DMARD therapy. These patients will then be followed-up for a period of 6 months or until flare of their arthritis activity, whichever is sooner.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DMARD cessation</intervention_name>
    <description>Complete cessation of non-biologic DMARD therapy (single or combination of methotrexate, sulphasalazine and/or hydroxychloroquine)</description>
    <arm_group_label>DMARD cessation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of rheumatoid arthritis made by consultant rheumatologist at least&#xD;
             12 months previously&#xD;
&#xD;
          -  Current single or combination use of methotrexate, sulphasalazine and/or&#xD;
             hydroxychloroquine&#xD;
&#xD;
          -  Arthritis currently in remission, as judged clinically by referring healthcare&#xD;
             professional&#xD;
&#xD;
          -  Willing to consider DMARD withdrawal&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of biologic therapy within the past 6 months&#xD;
&#xD;
          -  Received steroids within past 3 months (enteral, parenteral or intra-articular)&#xD;
&#xD;
          -  Use of any DMARD other than methotrexate, sulphasalazine or hydroxychloroquine within&#xD;
             the past 6 months (or past 12 months for leflunomide)&#xD;
&#xD;
          -  Current pregnancy, or pregnancy planned within next 6 months&#xD;
&#xD;
          -  Current participation within another clinical trial&#xD;
&#xD;
          -  Inability to provide informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John D Isaacs, PhD MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Newcastle University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Newcastle NIHR Clinical Research Facility, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust</name>
      <address>
        <city>Newcastle upon Tyne</city>
        <state>Tyne &amp; Wear</state>
        <zip>NE1 4LP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>August 15, 2014</study_first_submitted>
  <study_first_submitted_qc>August 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</study_first_posted>
  <last_update_submitted>November 1, 2017</last_update_submitted>
  <last_update_submitted_qc>November 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>rheumatoid arthritis</keyword>
  <keyword>biological markers</keyword>
  <keyword>remission</keyword>
  <keyword>ultrasonography</keyword>
  <keyword>microarray</keyword>
  <keyword>survival analysis</keyword>
  <keyword>T cell</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>
  </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/NCT02219347
org study id: NUTH7100
nct id: NCT02219347
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Rheumatoid arthritis is a common condition affecting approximately 1% of the United Kingdom
      population; it is an autoimmune disease where the body's natural defences (the immune system)
      attack the body itself resulting, most notably, in joint damage and arthritis. To help
      prevent this, patients with rheumatoid arthritis need to take disease-modifying
      anti-rheumatic drugs (DMARDs). As rheumatoid arthritis is a life-long condition, these drug
      treatments are prescribed as long-term medications taken for many years.

      With successful drug treatment, many patients are able to achieve an excellent control of
      their disease and their arthritis can go in to remission. At present, there are no markers
      which can reliably predict which of these patients can reduce their drug treatment, and hence
      benefit from a lower risk of side effects and inconvenience, without an increase in their
      arthritis activity.

      We invite patients with stable rheumatoid arthritis to participate in this study conducted by
      Newcastle upon Tyne Hospitals NHS Foundation Trust in collaboration with Newcastle University
      and funded by the Wellcome Trust. Patients whose arthritis is confirmed as being in remission
      will be able to stop their DMARD medication and be monitored for a period of 6 months.
      Patients whose arthritis activity increases during this time will be able to restart their
      DMARD medication, whereas those patients whose arthritis remains in remission will be able to
      stay off DMARD medication.

      The main aim of this study is to identify clinical, ultrasound and blood markers that can
      predict which patients will remain in remission after stopping DMARD medication. If
      identified, these markers could be a useful guide to doctors and patients in the future when
      deciding whether to stop DMARD therapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Time-to-flare of arthritis activity following DMARD cessation
time frame: From recruitment, assessed up to 6 months
description: Flare of arthritis activity defined as Disease Activity Score in 28 Joints C-Reactive Protein (DAS28-CRP) score greater than or equal to 2.4
measure: Clinical biomarkers predictive of DMARD-free remission
time frame: At recruitment
description: Baseline clinical factors predictive of time-to-flare of arthritis activity following DMARD cessation.
measure: Ultrasound biomarkers of DMARD-free remission
time frame: At recruitment
description: Baseline musculoskeletal ultrasound biomarkers predictive of time-to-flare of arthritis activity following DMARD cessation, including presence or absence of greyscale synovitis/tenosynovitis and erosions.
measure: Genetic biomarkers of DMARD-free remission
time frame: At recruitment
description: Baseline signature of differential gene expression in peripheral CD4+ T cells predictive of DMARD-free remission at 6 months following DMARD cessation, as measured using RNA sequencing.
measure: Cytokine biomarkers of DMARD-free remission
time frame: At recruitment
description: Baseline signature of differential cytokine levels in peripheral blood predictive of time-to-flare of arthritis activity, as measured using a multiplex cytokine assay.
measure: Rheumatoid arthritis disease activity
time frame: At recruitment and at 1 month, 3 months and 6 months following DMARD cessation
description: Measured by Disease Activity Score in 28 joints (DAS28-CRP) score.
measure: Physical disability
time frame: At baseline and at 6 months following DMARD cessation
description: Measured by Health Assessment Questionnaire Disability Index (HAQ-DI) questionnaire
arm group label: DMARD cessation
arm group type: Other
description: All patients recruited to the study who have a Disease Activity in 28 Joints C-Reactive Protein (DAS28-CRP) score of < 2.4 and who do not have power Doppler synovitis on a 7-joint musculoskeletal ultrasound scan will stop their DMARD therapy. These patients will then be followed-up for a period of 6 months or until flare of their arthritis activity, whichever is sooner.
intervention type: Drug
intervention name: DMARD cessation
description: Complete cessation of non-biologic DMARD therapy (single or combination of methotrexate, sulphasalazine and/or hydroxychloroquine)
arm group label: DMARD cessation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: John D Isaacs, PhD MBBS
role: Principal Investigator
affiliation: Newcastle University
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
sharing ipd: No