<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/NCT03011242</url>
  </required_header>
  <id_info>
    <org_study_id>RSRB 60239</org_study_id>
    <secondary_id>1R01AR069000-01</secondary_id>
    <nct_id>NCT03011242</nct_id>
  </id_info>
  <brief_title>DC-STAMP: Regulators of Osteoclastogenesis and Response Marker in PsA</brief_title>
  <official_title>DC-STAMP: Regulators of Osteoclastogenesis and Response Marker in PsA</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Rochester</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Rochester</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The Investigators will examine if DC-STAMP can serve as an early marker of TNFi response in&#xD;
      PsA. Identification of such a biomarker would permit rapid transition to a new agent, a major&#xD;
      treatment advance. TNFi are the most effective therapies in PsA, however, methotrexate is&#xD;
      frequently initiated early in the disease course based on its significantly lower cost.&#xD;
      Unfortunately, the efficacy of MTX has not been supported in clinical trials and up to 40% of&#xD;
      patients do not respond to TNFi therapy. Moreover, valid biomarkers to predict MTX or TNFi&#xD;
      responses are currently unavailable. This study may also provide the first data on the&#xD;
      comparative efficacy of MTX and TNFi using clinical, Ultrasound (US) and biomarker outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Psoriatic arthritis (PsA), an inflammatory joint disease associated with psoriasis (Ps),&#xD;
      affects approximately 650,000 adults in the United States and is associated with increased&#xD;
      morbidity and mortality. Bone damage develops in half these patients within the first two&#xD;
      years of the disease, often leaving them with impaired function and diminished quality of&#xD;
      life. The emergence of anti-Tumor Necrosis Factor therapies (TNFi) has dramatically improved&#xD;
      clinical response and slowed bone and cartilage degradation in PsA patients, however, only&#xD;
      50-60% of patients respond to these agents. To improve these outcomes, the investigators must&#xD;
      address two major gaps: a limited understanding of key events that underlie pathologic bone&#xD;
      destruction and the absence of biomarkers to predict biologic response and identify early&#xD;
      biologic responders to facilitate optimization of therapy.&#xD;
&#xD;
      Bone damage is mediated by osteoclasts which arise from monocyte precursors in the blood.&#xD;
      Osteoclast Precursors (OCPs) are dramatically increased in PsA, compared to controls,&#xD;
      particularly in patients with bone damage on X-ray. The number of these circulating precursor&#xD;
      cells dropped rapidly following treatment with TNFi. OCPs may serve as response biomarkers,&#xD;
      but cost, time and high variability limit these assays. Osteoclast precursors express&#xD;
      Dendritic Cell-Specific Transmembrane Protein (DC-STAMP), which is a seven-pass transmembrane&#xD;
      protein required for fusion of monocytes to form osteoclasts and giant cells. Monocyte&#xD;
      DC-STAMP levels dropped rapidly following treatment with TNFi. TNF receptor-associated factor&#xD;
      3 (TRAF3), an inhibitor of OC formation that correlates with extracellular TNF&#xD;
      concentrations, is elevated in OCPs from PsA patients. These markers may predict TNFi&#xD;
      treatment response.&#xD;
&#xD;
      The goal of this study is to examine DC-STAMP in Psoriatic Arthritis patients prior to and&#xD;
      after starting standard of care treatment with a TNFi or non-biologic DMARD. We will also&#xD;
      examine PsA patients with low disease activity on standard of care TNFi and PsA patients with&#xD;
      low disease activity on standard of care non-biologic DMARDs will serve as controls.&#xD;
&#xD;
      Three groups of subjects will be recruited.&#xD;
&#xD;
        1. Longitudinal: 30 subjects starting out on standard of care treatment with a TNFi or&#xD;
           non-biologic DMARD will take part in the longitudinal section of the study. Subjects may&#xD;
           be asked to have a blood draw at one additional visit before starting therapy for&#xD;
           additional research assays if they are DC-STAMP positive. If the longitudinal subjects&#xD;
           that return for an additional blood draw before starting medication have unusable sample&#xD;
           data, they will be replaced by additional longitudinal subjects out of the 30 enrolled&#xD;
           longitudinal participants to get sufficient data results of two subjects. The subjects&#xD;
           with unusable data will continue in the longitudinal follow up study visits as intended.&#xD;
&#xD;
        2. Cross sectional: 36 patients will take part in the cross-sectional part of the study. 18&#xD;
           patients on stable non-biologic DMARDS and 18 patients on stable TNFi will be compared&#xD;
           in the cross-sectional part. This population should be in good disease state such that&#xD;
           their disease is controlled and treatment will not need to be changed. If longitudinal&#xD;
           subjects fit the cross-sectional criteria and wish to participate, they will be&#xD;
           re-consented for the cross-sectional part of the study.&#xD;
&#xD;
           While 66 subjects will be studied in both the longitudinal and cross-sectional studies&#xD;
           combined, up to 80 PsA subjects may be consented to allow for screen failures and to&#xD;
           replace longitudinal subjects who withdraw or are lost to follow-up.&#xD;
&#xD;
        3. Assay Development: Up to 40 PsA or healthy subjects may be enrolled for blood draw for&#xD;
           assay development and to test development of techniques for ultrasound comparison and&#xD;
           scoring system validation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 11, 2017</start_date>
  <completion_date type="Actual">June 30, 2021</completion_date>
  <primary_completion_date type="Actual">June 30, 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>Assessing the Change of DC-STAMP as an early TNFi response biomarker.</measure>
    <time_frame>Baseline to 2 weeks of standard of care treatment</time_frame>
    <description>The Investigators will analyze the change in DC-STAMP expression from baseline to 2 weeks using flow cytometry.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessing the Change of Clinical Response at 16 weeks.</measure>
    <time_frame>Baseline to 16 weeks of standard of care treatment</time_frame>
    <description>The Investigators will measure clinical response from baseline to 16 weeks using the Disease Activity Index for Psoriatic Arthritis (DAPSA). The cutoff points for the classification of disease activity states for the DAPSA are:&#xD;
remission less than or equal to 4, low disease activity 4-14, moderate disease activity 14-28, high disease activity &gt;28</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">47</enrollment>
  <condition>Psoriatic Arthritis</condition>
  <arm_group>
    <arm_group_label>Longitudinal Cohort: Psoriatic Arthritis</arm_group_label>
    <description>Individuals diagnosed with Psoriatic Arthritis starting standard of care treatment with a TNFi or non-biologic DMARD.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Assay Development: Healthy or Psoriatic Arthritis</arm_group_label>
    <description>Individuals that are healthy or with a diagnosis of Psoriatic Arthritis will be enrolled for blood draws for assay development and/or for an ultrasound for development of techniques and scoring system validation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cross-Sectional: Psoriatic Arthritis</arm_group_label>
    <description>Individuals diagnosed with Psoriatic Arthritis in good disease state on stable non-biologic DMARDS or on stable TNFi.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      If patient consents, peripheral blood samples that remain after study assays are completed&#xD;
      may be stored for future non-genetic research.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Male and female subjects that are 18 years old and older. Due to the demographic&#xD;
        distribution of the disease the investigators expect all or nearly all subjects to be&#xD;
        caucasian, however no subjects will be excluded based on race or ethnic origin.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability to provide written informed consent.&#xD;
&#xD;
          -  Subjects can be of either gender but must be at least 18 years old.&#xD;
&#xD;
          -  Subjects with PsA should fulfill CASPAR criteria.&#xD;
&#xD;
               -  Longitudinal: Patients with active PsA who will be starting a TNFi or&#xD;
                  non-biologic DMARD treatment (Subjects starting non-biologic DMARDS can have&#xD;
                  their blood drawn within the first few days of starting therapy).&#xD;
&#xD;
               -  Additional Blood Draw: Positive DC-STAMP signal at baseline&#xD;
&#xD;
               -  Cross-Sectional: Patients on stable DMARDS or TNFi for more than 16 weeks.&#xD;
&#xD;
               -  Healthy Subjects: Healthy controls should have no active systemic disorders or&#xD;
                  inflammatory conditions that would confound the results of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to donate blood because of poor venous access or intolerance of phlebotomy.&#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>Christopher Ritchlin, MD/MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Univerisity of Rochester</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Rochester Medical Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.urmc.rochester.edu/medicine/allergy/patients-families/clinical-trials.aspx</url>
    <description>URMC Allergy, Immunology &amp; Rheumatology Clinical Trials</description>
  </link>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>September 20, 2016</study_first_submitted>
  <study_first_submitted_qc>January 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>August 12, 2021</last_update_submitted>
  <last_update_submitted_qc>August 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Rochester</investigator_affiliation>
    <investigator_full_name>Christopher Ritchlin</investigator_full_name>
    <investigator_title>M.D.; M.P.H.; Professor of Medicine, Chief of Allergy, Immunology &amp; Rheumatology Division</investigator_title>
  </responsible_party>
  <keyword>Psoriatic Arthritis</keyword>
  <keyword>US</keyword>
  <keyword>DC-STAMP</keyword>
  <keyword>Osteoclast Precursor (OCPs)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Psoriatic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Samples of any type collected at the University of Rochester may be shared with researchers at other institutions. Subjects will be made aware of this in the informed consent form.</ipd_description>
    <ipd_time_frame>Once a subject signs the consent form to allow for sharing, if any samples remain after all tests are completed, the samples will be stored for future research indefinitely or until the subject cancels consent to share.</ipd_time_frame>
    <ipd_access_criteria>Investigators at other collaborating institutions may have access to leftover samples and data. Data will not include any information that is identifying.</ipd_access_criteria>
  </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/NCT03011242
org study id: RSRB 60239
secondary id: 1R01AR069000-01
nct id: NCT03011242
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The Investigators will examine if DC-STAMP can serve as an early marker of TNFi response in
      PsA. Identification of such a biomarker would permit rapid transition to a new agent, a major
      treatment advance. TNFi are the most effective therapies in PsA, however, methotrexate is
      frequently initiated early in the disease course based on its significantly lower cost.
      Unfortunately, the efficacy of MTX has not been supported in clinical trials and up to 40% of
      patients do not respond to TNFi therapy. Moreover, valid biomarkers to predict MTX or TNFi
      responses are currently unavailable. This study may also provide the first data on the
      comparative efficacy of MTX and TNFi using clinical, Ultrasound (US) and biomarker outcomes.
Psoriatic arthritis (PsA), an inflammatory joint disease associated with psoriasis (Ps),
      affects approximately 650,000 adults in the United States and is associated with increased
      morbidity and mortality. Bone damage develops in half these patients within the first two
      years of the disease, often leaving them with impaired function and diminished quality of
      life. The emergence of anti-Tumor Necrosis Factor therapies (TNFi) has dramatically improved
      clinical response and slowed bone and cartilage degradation in PsA patients, however, only
      50-60% of patients respond to these agents. To improve these outcomes, the investigators must
      address two major gaps: a limited understanding of key events that underlie pathologic bone
      destruction and the absence of biomarkers to predict biologic response and identify early
      biologic responders to facilitate optimization of therapy.

      Bone damage is mediated by osteoclasts which arise from monocyte precursors in the blood.
      Osteoclast Precursors (OCPs) are dramatically increased in PsA, compared to controls,
      particularly in patients with bone damage on X-ray. The number of these circulating precursor
      cells dropped rapidly following treatment with TNFi. OCPs may serve as response biomarkers,
      but cost, time and high variability limit these assays. Osteoclast precursors express
      Dendritic Cell-Specific Transmembrane Protein (DC-STAMP), which is a seven-pass transmembrane
      protein required for fusion of monocytes to form osteoclasts and giant cells. Monocyte
      DC-STAMP levels dropped rapidly following treatment with TNFi. TNF receptor-associated factor
      3 (TRAF3), an inhibitor of OC formation that correlates with extracellular TNF
      concentrations, is elevated in OCPs from PsA patients. These markers may predict TNFi
      treatment response.

      The goal of this study is to examine DC-STAMP in Psoriatic Arthritis patients prior to and
      after starting standard of care treatment with a TNFi or non-biologic DMARD. We will also
      examine PsA patients with low disease activity on standard of care TNFi and PsA patients with
      low disease activity on standard of care non-biologic DMARDs will serve as controls.

      Three groups of subjects will be recruited.

        1. Longitudinal: 30 subjects starting out on standard of care treatment with a TNFi or
           non-biologic DMARD will take part in the longitudinal section of the study. Subjects may
           be asked to have a blood draw at one additional visit before starting therapy for
           additional research assays if they are DC-STAMP positive. If the longitudinal subjects
           that return for an additional blood draw before starting medication have unusable sample
           data, they will be replaced by additional longitudinal subjects out of the 30 enrolled
           longitudinal participants to get sufficient data results of two subjects. The subjects
           with unusable data will continue in the longitudinal follow up study visits as intended.

        2. Cross sectional: 36 patients will take part in the cross-sectional part of the study. 18
           patients on stable non-biologic DMARDS and 18 patients on stable TNFi will be compared
           in the cross-sectional part. This population should be in good disease state such that
           their disease is controlled and treatment will not need to be changed. If longitudinal
           subjects fit the cross-sectional criteria and wish to participate, they will be
           re-consented for the cross-sectional part of the study.

           While 66 subjects will be studied in both the longitudinal and cross-sectional studies
           combined, up to 80 PsA subjects may be consented to allow for screen failures and to
           replace longitudinal subjects who withdraw or are lost to follow-up.

        3. Assay Development: Up to 40 PsA or healthy subjects may be enrolled for blood draw for
           assay development and to test development of techniques for ultrasound comparison and
           scoring system validation.
observational model: Case-Control
time perspective: Prospective
measure: Assessing the Change of DC-STAMP as an early TNFi response biomarker.
time frame: Baseline to 2 weeks of standard of care treatment
description: The Investigators will analyze the change in DC-STAMP expression from baseline to 2 weeks using flow cytometry.
measure: Assessing the Change of Clinical Response at 16 weeks.
time frame: Baseline to 16 weeks of standard of care treatment
description: The Investigators will measure clinical response from baseline to 16 weeks using the Disease Activity Index for Psoriatic Arthritis (DAPSA). The cutoff points for the classification of disease activity states for the DAPSA are:
remission less than or equal to 4, low disease activity 4-14, moderate disease activity 14-28, high disease activity >28
arm group label: Longitudinal Cohort: Psoriatic Arthritis
description: Individuals diagnosed with Psoriatic Arthritis starting standard of care treatment with a TNFi or non-biologic DMARD.
arm group label: Assay Development: Healthy or Psoriatic Arthritis
description: Individuals that are healthy or with a diagnosis of Psoriatic Arthritis will be enrolled for blood draws for assay development and/or for an ultrasound for development of techniques and scoring system validation.
arm group label: Cross-Sectional: Psoriatic Arthritis
description: Individuals diagnosed with Psoriatic Arthritis in good disease state on stable non-biologic DMARDS or on stable TNFi.
If patient consents, peripheral blood samples that remain after study assays are completed
      may be stored for future non-genetic research.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Christopher Ritchlin, MD/MPH
role: Principal Investigator
affiliation: Univerisity of Rochester
facility: 
country: United States
url: https://www.urmc.rochester.edu/medicine/allergy/patients-families/clinical-trials.aspx
description: URMC Allergy, Immunology & Rheumatology Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: University of Rochester
investigator full name: Christopher Ritchlin
investigator title: M.D.; M.P.H.; Professor of Medicine, Chief of Allergy, Immunology & Rheumatology Division
mesh term: Arthritis
mesh term: Arthritis, Psoriatic
sharing ipd: Yes
ipd description: Samples of any type collected at the University of Rochester may be shared with researchers at other institutions. Subjects will be made aware of this in the informed consent form.
ipd time frame: Once a subject signs the consent form to allow for sharing, if any samples remain after all tests are completed, the samples will be stored for future research indefinitely or until the subject cancels consent to share.
ipd access criteria: Investigators at other collaborating institutions may have access to leftover samples and data. Data will not include any information that is identifying.