<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/NCT03778515</url>
  </required_header>
  <id_info>
    <org_study_id>18-1327</org_study_id>
    <nct_id>NCT03778515</nct_id>
  </id_info>
  <brief_title>Novel Quantitative MRI for Axial Spondyloarthritis</brief_title>
  <official_title>Novel Quantitative MRI for Axial Spondyloarthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>UCB PHARMA Inc. (US)</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>The Cleveland Clinic</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This proposal aims to develop novel MR imaging and image processing techniques that will&#xD;
      provide reliable and fully quantitative evaluation of inflammation, chronic structural&#xD;
      changes and vascularity in patients with Ankylosing Spondylitis (AS). The quantitative&#xD;
      evaluation will be more objective and reproducible, more sensitive to subtle changes, and&#xD;
      less time consuming, as compared to the current semi-quantitative evaluation. It will allow&#xD;
      radiologists and rheumatologists to evaluate the inflammation and structural changes more&#xD;
      reliably to improve early diagnosis and treatment response evaluation. The developed&#xD;
      quantification tools can be disseminated to other research and clinical sites for&#xD;
      retrospective and prospective data analysis, and used as outcome measures for future&#xD;
      multi-center trials. The evaluation of vascularity will enhance Investigators understanding&#xD;
      of disease pathophysiology and serve as a novel marker to improve investigators capability of&#xD;
      evaluating and predicting treatment response in AS. The successful implementation will&#xD;
      greatly assist clinicians to optimize individualized therapeutic strategies and ultimately&#xD;
      improve patient care for AS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There is a critical and unmet clinical need for non-invasive techniques that provide early&#xD;
      diagnosis as well as reliable and sensitive evaluations of ongoing disease activity and&#xD;
      treatment response in patients with axial spondyloarthritis (axSpA). Imaging plays a key role&#xD;
      to fulfill this goal and there is an increasing trend of applying imaging techniques in the&#xD;
      field of axSpA. However, current imaging techniques, including radiographs and MRI, are&#xD;
      primarily limited to qualitative or semi-quantitative evaluations of disease activity and&#xD;
      structural damage, which is very crude and subjective with considerable inter-reader&#xD;
      variation, and has limited sensitivity of detecting early lesions as well as changes in&#xD;
      inflammatory lesions beyond morphology of bone marrow edema after treatment. Furthermore,&#xD;
      several recent studies reported data of inflammation (bone marrow edema), fatty deposition&#xD;
      and new bone formation after TNF inhibitor (TNFi) treatment in patients with axSpA,&#xD;
      suggesting a complex relationship between inflammation, bone formation, and suppression of&#xD;
      the TNF pathway. These studies also call for differentiating edema for their characteristics&#xD;
      (angiogenesis for example) and inflammation stages (acute and chronic), which will provide&#xD;
      valuable insight on disease pathophysiology as well as on optimizing treatment for individual&#xD;
      patients with axSpA.&#xD;
&#xD;
      The long-term goal is to develop novel quantitative MRI measures that will reliably assess&#xD;
      both inflammation and structural damage, and predict treatment response, remission and&#xD;
      disease progression in axSpA. Compared to current MRI grading systems, such quantitative&#xD;
      measures may be used as more sensitive, specific, reliable and faster imaging markers for&#xD;
      future trials, and eventually for clinical practice to improve patient management in axSpA.&#xD;
      In this proposal, Investigators will focus on patients with clinically diagnosed active&#xD;
      Ankylosing Spondylitis (AS) and will develop novel imaging and image processing techniques&#xD;
      using 3 Tesla MRI. The specific aims are two-folds. Firstly, Investigators will develop&#xD;
      methods that reliably quantify bone marrow edema (BME), fatty deposition (FD) and erosions;&#xD;
      Secondly, Investigators will develop novel quantitative evaluation of perfusion and&#xD;
      vascularity of BME (using dynamic Gd-enhanced MRI), which has not been investigated for axSpA&#xD;
      in the literature.&#xD;
&#xD;
      Investigators will recruit 20 patients with active Ankylosing Spondylitis (AS) using the 1984&#xD;
      modified NY criteria. Fifteen patients will be recruited from the Ankylosing Spondylitis&#xD;
      clinic at UCSF, directed by Dr. Lianne Gensler, and five patients will be recruited from&#xD;
      Rheumatology clinic at the Cleveland Clinic by Dr. Elaine Husni. Drs. Gensler and Husni will&#xD;
      also reach out to the other academic sites and the community private practices to recruit&#xD;
      patients as needed who are starting TNF inhibitor therapy with CZP for their AS. Patients&#xD;
      will be studied at baseline, 4-weeks and 48-weeks after initiation of TNFi treatment.&#xD;
      Advanced quantitative MRI will be applied to evaluate early treatment response at 4-weeks,&#xD;
      and long-term outcomes at 48-weeks. The central hypothesis is that quantitative MRI allows a&#xD;
      fast, specific and reproducible evaluation of disease activity and structural changes in AS,&#xD;
      and provides more superior diagnostic and prognostic capability compared to semi-quantitative&#xD;
      MRI grading systems.&#xD;
&#xD;
      The successful implementation of the proposed study will make significant contributions to&#xD;
      the research and clinical&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of enrollment due to the pandemic&#xD;
  </why_stopped>
  <start_date type="Actual">January 15, 2020</start_date>
  <completion_date type="Actual">July 31, 2021</completion_date>
  <primary_completion_date type="Actual">July 31, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Volume of MRI bone marrow edema (in cm^3) from Baseline at 48-weeks</measure>
    <time_frame>Change from Baseline at 48-weeks</time_frame>
    <description>Fully quantitative evaluation of volume of bone marrow edema (in cm^3) will be developed and applied in the study. Volume of BME will be calculated in both SIJ and Spine in high-resolution MR images to evaluate the active inflammation in the patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in MRI grading SPARCC from Baseline at 48-weeks</measure>
    <time_frame>Change from Baseline at 48-weeks</time_frame>
    <description>Inflammation and structural damages, including bone marrow edema, fatty deposition, erosions, syndesmophytes and ankylosis, in the spine and SIJs will be graded in MR images by certified radiologists using validated scoring systems developed by the Spondyloarthritis Research Consortium of Canada (SPARCC).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in C-reactive protein (CRP) (in mg/dL) from Baseline at 48-weeks</measure>
    <time_frame>Change from Baseline at 48-weeks</time_frame>
    <description>CRP will be measured for evaluating inflammation activity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP at Baseline, 4-weeks, 48-weeks</measure>
    <time_frame>Change from Baseline at 48-weeks</time_frame>
    <description>The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite index to assess disease activity in Ankylosing Spondylitis (AS). It combines five disease activity variables with only partial overlap, resulting in one single score with better truth (validity), enhanced discriminative capacity and improved sensitivity to change as compared to single-item variables. ASDAS-CRP will be calculated as 0.12 x Back Pain + 0.06 x Duration of Morning Stiffness + 0.11 x Patient Global + 0.07 x Peripheral Pain/Swelling + 0.58 x Ln(CRP+1).</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">1</enrollment>
  <condition>Spondylitis, Ankylosing</condition>
  <arm_group>
    <arm_group_label>Cases - Ankylosing Spondylitis Cohort</arm_group_label>
    <description>20 patients with ankylosing spondylitis (AS). Fifteen of these patients will be recruited from the Ankylosing Spondylitis clinic at the University of California, San Francisco. Five patients will be recruited from the Rheumatology clinic at the Cleveland Clinic. Observational with MRI.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls - w/o Ankylosing Spondylitis</arm_group_label>
    <description>5 patients without AS and with no history of any arthritis or lower back pain in this study. These 5 patients will make up the control group of the study, which means that they will provide a benchmark of comparison for the results investigators obtain from the active AS group. 2 of these 5 patients will be recruited from Cleveland Clinic, and 3 will be recruited from UCSF. Observational with MRI</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>MRI</intervention_name>
    <description>Observational Study of novel MR imaging and image processing techniques that will provide reliable and fully quantitative evaluation of inflammation, chronic structural changes and vascularity in patients with Ankylosing Spondylitis (AS).</description>
    <arm_group_label>Cases - Ankylosing Spondylitis Cohort</arm_group_label>
    <arm_group_label>Controls - w/o Ankylosing Spondylitis</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        15 patients will be recruited from the Ankylosing Spondylitis clinic at UCSF, and five&#xD;
        patients will be recruited from Rheumatology clinic at the Cleveland Clinic. 10 patients&#xD;
        with disease duration &lt;= 10 years, and ten patients with disease duration &gt; 10 years but&#xD;
        without complete ankylosis. 5 healthy controls will be recruited for evaluating the&#xD;
        measurement, with 2 from CCF and 3 from UCSF. The volunteers will be studied at baseline&#xD;
        and 1-year follow up.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Active AS meeting the modified New York criteria&#xD;
&#xD;
          -  BASDAI ≥ 4&#xD;
&#xD;
          -  Elevated C-Reactive Protein&#xD;
&#xD;
          -  ≥ 18 years old&#xD;
&#xD;
          -  Initiation of TNFi treatment with CZP&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous treatment with more than one biologics&#xD;
&#xD;
          -  Biologic treatment within six-months (no more than 20% of group (n=4) for patients&#xD;
             with previous biologic treatment)&#xD;
&#xD;
          -  Non-response to previous anti TNF treatment&#xD;
&#xD;
          -  Fibromyalgia or other reasons for back pain&#xD;
&#xD;
          -  Pregnant patients&#xD;
&#xD;
          -  Patients on &gt; 10mg of Prednisone per day&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xiaojuan Li, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Cleveland Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>August 30, 2022</last_update_submitted>
  <last_update_submitted_qc>August 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
    <investigator_full_name>Xiaojuan Li</investigator_full_name>
    <investigator_title>Xiaojuan Li, PhD, Professor, Department of Biomedical Engineering</investigator_title>
  </responsible_party>
  <keyword>Axial</keyword>
  <keyword>Spondyloarthritis</keyword>
  <keyword>MRI</keyword>
  <keyword>Ankylosing Spondylitis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spondylitis</mesh_term>
    <mesh_term>Spondylarthritis</mesh_term>
    <mesh_term>Axial Spondyloarthritis</mesh_term>
    <mesh_term>Spondylitis, Ankylosing</mesh_term>
  </condition_browse>
  <!-- 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/NCT03778515
org study id: 18-1327
nct id: NCT03778515
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This proposal aims to develop novel MR imaging and image processing techniques that will
      provide reliable and fully quantitative evaluation of inflammation, chronic structural
      changes and vascularity in patients with Ankylosing Spondylitis (AS). The quantitative
      evaluation will be more objective and reproducible, more sensitive to subtle changes, and
      less time consuming, as compared to the current semi-quantitative evaluation. It will allow
      radiologists and rheumatologists to evaluate the inflammation and structural changes more
      reliably to improve early diagnosis and treatment response evaluation. The developed
      quantification tools can be disseminated to other research and clinical sites for
      retrospective and prospective data analysis, and used as outcome measures for future
      multi-center trials. The evaluation of vascularity will enhance Investigators understanding
      of disease pathophysiology and serve as a novel marker to improve investigators capability of
      evaluating and predicting treatment response in AS. The successful implementation will
      greatly assist clinicians to optimize individualized therapeutic strategies and ultimately
      improve patient care for AS.
There is a critical and unmet clinical need for non-invasive techniques that provide early
      diagnosis as well as reliable and sensitive evaluations of ongoing disease activity and
      treatment response in patients with axial spondyloarthritis (axSpA). Imaging plays a key role
      to fulfill this goal and there is an increasing trend of applying imaging techniques in the
      field of axSpA. However, current imaging techniques, including radiographs and MRI, are
      primarily limited to qualitative or semi-quantitative evaluations of disease activity and
      structural damage, which is very crude and subjective with considerable inter-reader
      variation, and has limited sensitivity of detecting early lesions as well as changes in
      inflammatory lesions beyond morphology of bone marrow edema after treatment. Furthermore,
      several recent studies reported data of inflammation (bone marrow edema), fatty deposition
      and new bone formation after TNF inhibitor (TNFi) treatment in patients with axSpA,
      suggesting a complex relationship between inflammation, bone formation, and suppression of
      the TNF pathway. These studies also call for differentiating edema for their characteristics
      (angiogenesis for example) and inflammation stages (acute and chronic), which will provide
      valuable insight on disease pathophysiology as well as on optimizing treatment for individual
      patients with axSpA.

      The long-term goal is to develop novel quantitative MRI measures that will reliably assess
      both inflammation and structural damage, and predict treatment response, remission and
      disease progression in axSpA. Compared to current MRI grading systems, such quantitative
      measures may be used as more sensitive, specific, reliable and faster imaging markers for
      future trials, and eventually for clinical practice to improve patient management in axSpA.
      In this proposal, Investigators will focus on patients with clinically diagnosed active
      Ankylosing Spondylitis (AS) and will develop novel imaging and image processing techniques
      using 3 Tesla MRI. The specific aims are two-folds. Firstly, Investigators will develop
      methods that reliably quantify bone marrow edema (BME), fatty deposition (FD) and erosions;
      Secondly, Investigators will develop novel quantitative evaluation of perfusion and
      vascularity of BME (using dynamic Gd-enhanced MRI), which has not been investigated for axSpA
      in the literature.

      Investigators will recruit 20 patients with active Ankylosing Spondylitis (AS) using the 1984
      modified NY criteria. Fifteen patients will be recruited from the Ankylosing Spondylitis
      clinic at UCSF, directed by Dr. Lianne Gensler, and five patients will be recruited from
      Rheumatology clinic at the Cleveland Clinic by Dr. Elaine Husni. Drs. Gensler and Husni will
      also reach out to the other academic sites and the community private practices to recruit
      patients as needed who are starting TNF inhibitor therapy with CZP for their AS. Patients
      will be studied at baseline, 4-weeks and 48-weeks after initiation of TNFi treatment.
      Advanced quantitative MRI will be applied to evaluate early treatment response at 4-weeks,
      and long-term outcomes at 48-weeks. The central hypothesis is that quantitative MRI allows a
      fast, specific and reproducible evaluation of disease activity and structural changes in AS,
      and provides more superior diagnostic and prognostic capability compared to semi-quantitative
      MRI grading systems.

      The successful implementation of the proposed study will make significant contributions to
      the research and clinical
observational model: Case-Control
time perspective: Prospective
measure: Change in Volume of MRI bone marrow edema (in cm^3) from Baseline at 48-weeks
time frame: Change from Baseline at 48-weeks
description: Fully quantitative evaluation of volume of bone marrow edema (in cm^3) will be developed and applied in the study. Volume of BME will be calculated in both SIJ and Spine in high-resolution MR images to evaluate the active inflammation in the patients.
measure: Change in MRI grading SPARCC from Baseline at 48-weeks
time frame: Change from Baseline at 48-weeks
description: Inflammation and structural damages, including bone marrow edema, fatty deposition, erosions, syndesmophytes and ankylosis, in the spine and SIJs will be graded in MR images by certified radiologists using validated scoring systems developed by the Spondyloarthritis Research Consortium of Canada (SPARCC).
measure: Change in C-reactive protein (CRP) (in mg/dL) from Baseline at 48-weeks
time frame: Change from Baseline at 48-weeks
description: CRP will be measured for evaluating inflammation activity.
measure: Change in Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP at Baseline, 4-weeks, 48-weeks
time frame: Change from Baseline at 48-weeks
description: The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite index to assess disease activity in Ankylosing Spondylitis (AS). It combines five disease activity variables with only partial overlap, resulting in one single score with better truth (validity), enhanced discriminative capacity and improved sensitivity to change as compared to single-item variables. ASDAS-CRP will be calculated as 0.12 x Back Pain + 0.06 x Duration of Morning Stiffness + 0.11 x Patient Global + 0.07 x Peripheral Pain/Swelling + 0.58 x Ln(CRP+1).
arm group label: Cases - Ankylosing Spondylitis Cohort
description: 20 patients with ankylosing spondylitis (AS). Fifteen of these patients will be recruited from the Ankylosing Spondylitis clinic at the University of California, San Francisco. Five patients will be recruited from the Rheumatology clinic at the Cleveland Clinic. Observational with MRI.
arm group label: Controls - w/o Ankylosing Spondylitis
description: 5 patients without AS and with no history of any arthritis or lower back pain in this study. These 5 patients will make up the control group of the study, which means that they will provide a benchmark of comparison for the results investigators obtain from the active AS group. 2 of these 5 patients will be recruited from Cleveland Clinic, and 3 will be recruited from UCSF. Observational with MRI
intervention type: Diagnostic Test
intervention name: MRI
description: Observational Study of novel MR imaging and image processing techniques that will provide reliable and fully quantitative evaluation of inflammation, chronic structural changes and vascularity in patients with Ankylosing Spondylitis (AS).
arm group label: Cases - Ankylosing Spondylitis Cohort
arm group label: Controls - w/o Ankylosing Spondylitis
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Xiaojuan Li, PhD
role: Principal Investigator
affiliation: The Cleveland Clinic
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: The Cleveland Clinic
investigator full name: Xiaojuan Li
investigator title: Xiaojuan Li, PhD, Professor, Department of Biomedical Engineering
mesh term: Spondylitis
mesh term: Spondylarthritis
mesh term: Axial Spondyloarthritis
mesh term: Spondylitis, Ankylosing