<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/NCT02212262</url>
  </required_header>
  <id_info>
    <org_study_id>IUCRO-0498</org_study_id>
    <nct_id>NCT02212262</nct_id>
  </id_info>
  <brief_title>Role of Osteocytes in Myeloma Bone Disease</brief_title>
  <official_title>Role of Osteocytes in Myeloma Bone Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Attaya Suvannasankha</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Indiana University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Progress in the treatment of myeloma and myeloma bone disease has substantially increased&#xD;
      overall survival, but relapse is inevitable and better treatment is needed. The bone&#xD;
      microenvironment is tremendously complex, so that targeting single interactions between tumor&#xD;
      and bone is unlikely to be effective. Treatments need to block centrally important,&#xD;
      multifunctional pathways. The investigators data point to a central role of the osteocyte to&#xD;
      induce heparanase, a multifunctional mediator of myeloma bone disease. Increased heparanase&#xD;
      due to FGF23 may make systemic inhibitors of heparanase less effective in bone than&#xD;
      elsewhere. FGF23 neutralizing antibodies have been developed for non-cancer conditions of&#xD;
      FGF23 excess, such as chronic kidney disease (Shimada &amp; Fukamoto, 2012), and could be used in&#xD;
      MM alone or in combination with heparanase inhibitors. Complete neutralization of FGF23 has&#xD;
      adverse effects, but neutralization of FGF23 excess may be practical, or in the future,&#xD;
      suppression of excess FGF23 biosynthesis by osteocytes.&#xD;
&#xD;
      The investigators hope to determine serum FGF23 and heparanase, Dkk1 and plasma klotho levels&#xD;
      in patients with newly diagnosed and relapsed myeloma compared to healthy controls with this&#xD;
      exploratory study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 7, 2014</start_date>
  <completion_date type="Actual">February 5, 2022</completion_date>
  <primary_completion_date type="Actual">February 5, 2022</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>Molecular interactions between multiple myeloma and osteocytes</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>To determine FGF23 and heparanase, Dkk1 and plasma klotho levels increase in patients with newly diagnosed and relapsed myeloma compared to healthy controls.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Multiple Myeloma osteocytes and tumor staging</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>To correlate the FGF23, heparanase, Dkk1 and plasma klotho to tumor staging</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multiple Myeloma osteocytes and Type I collagen fragments on bone resorption</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>To correlate the FGF23, heparanase, Dkk1 and plasma klotho to extent of bone resorption using serum type I collagen fragments ICTP and CTX</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">67</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Multiple Myeloma Patients</arm_group_label>
    <description>Patients with multiple myeloma will undergo a blood draw and a bone marrow aspirate. Extra bone marrow will be taken for study purposes only.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy subjects</arm_group_label>
    <description>Healthy subjects and multiple myeloma patients will undergo a blood draw</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Oncology Clinics at Indiana University Roudebuch VA Medical Center Community sample&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age &gt; 18 years but ≤ 95 years at the time of consent&#xD;
&#xD;
          2. Subjects must be English-speaking&#xD;
&#xD;
          3. Must voluntarily sign the most current informed consent and HIPAA documents prior to&#xD;
             study participation.&#xD;
&#xD;
          4. Have no prior history of malignancy in the past 5 years with the exception of basal&#xD;
             cell and squamous cell carcinoma of the skin. Other cancers with low potential for&#xD;
             metastasis, such as in situ cancers can also be enrolled as healthy volunteers.&#xD;
&#xD;
          5. Have no known liver or kidney disorders&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant females will be excluded from the study.&#xD;
&#xD;
          2. Subjects allergic to xylocaine will be excluded.&#xD;
&#xD;
          3. Subjects with an acute illness (Ex. upper respiratory infection, viral illness) in the&#xD;
             past seven days will be excluded.&#xD;
&#xD;
          4. History of bleeding disorders.&#xD;
&#xD;
          5. Subjects deemed incompetent by treating physician&#xD;
&#xD;
          6. Institutionalized, mentally disabled subjects&#xD;
&#xD;
          7. Subjects who are prisoners&#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>Attaya Suvannasankha, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Indiana University Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Roudebush Medical Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>July 31, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2014</study_first_posted>
  <last_update_submitted>September 5, 2023</last_update_submitted>
  <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Indiana University School of Medicine</investigator_affiliation>
    <investigator_full_name>Attaya Suvannasankha</investigator_full_name>
    <investigator_title>Assistant Professor of Clinical Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
    <mesh_term>Bone Diseases</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/NCT02212262
org study id: IUCRO-0498
nct id: NCT02212262
lead sponsor: 
has dmc: Yes
Progress in the treatment of myeloma and myeloma bone disease has substantially increased
      overall survival, but relapse is inevitable and better treatment is needed. The bone
      microenvironment is tremendously complex, so that targeting single interactions between tumor
      and bone is unlikely to be effective. Treatments need to block centrally important,
      multifunctional pathways. The investigators data point to a central role of the osteocyte to
      induce heparanase, a multifunctional mediator of myeloma bone disease. Increased heparanase
      due to FGF23 may make systemic inhibitors of heparanase less effective in bone than
      elsewhere. FGF23 neutralizing antibodies have been developed for non-cancer conditions of
      FGF23 excess, such as chronic kidney disease (Shimada & Fukamoto, 2012), and could be used in
      MM alone or in combination with heparanase inhibitors. Complete neutralization of FGF23 has
      adverse effects, but neutralization of FGF23 excess may be practical, or in the future,
      suppression of excess FGF23 biosynthesis by osteocytes.

      The investigators hope to determine serum FGF23 and heparanase, Dkk1 and plasma klotho levels
      in patients with newly diagnosed and relapsed myeloma compared to healthy controls with this
      exploratory study.
observational model: Case-Control
time perspective: Prospective
measure: Molecular interactions between multiple myeloma and osteocytes
time frame: Up to 4 years
description: To determine FGF23 and heparanase, Dkk1 and plasma klotho levels increase in patients with newly diagnosed and relapsed myeloma compared to healthy controls.
measure: Multiple Myeloma osteocytes and tumor staging
time frame: Up to 4 years
description: To correlate the FGF23, heparanase, Dkk1 and plasma klotho to tumor staging
measure: Multiple Myeloma osteocytes and Type I collagen fragments on bone resorption
time frame: Up to 4 years
description: To correlate the FGF23, heparanase, Dkk1 and plasma klotho to extent of bone resorption using serum type I collagen fragments ICTP and CTX
arm group label: Multiple Myeloma Patients
description: Patients with multiple myeloma will undergo a blood draw and a bone marrow aspirate. Extra bone marrow will be taken for study purposes only.
arm group label: Healthy subjects
description: Healthy subjects and multiple myeloma patients will undergo a blood draw
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: Attaya Suvannasankha, M.D.
role: Principal Investigator
affiliation: Indiana University
facility: 
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Indiana University School of Medicine
investigator full name: Attaya Suvannasankha
investigator title: Assistant Professor of Clinical Medicine
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Bone Diseases