<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/NCT03029442</url>
  </required_header>
  <id_info>
    <org_study_id>BAU-16-057</org_study_id>
    <nct_id>NCT03029442</nct_id>
  </id_info>
  <brief_title>The Efficacy of Denosumab in Incomplete Patients Spinal Cord Injury</brief_title>
  <official_title>The Efficacy of Denosumab to Prevent Bone Loss in Ambulatory and Non-ambulatory Motor-Incomplete Patients With Subacute Spinal Cord Injury</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>James J. Peters Veterans Affairs Medical Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Kessler Institute for Rehabilitation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>James J. Peters Veterans Affairs Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the usefulness of a drug, denosumab, to prevent the&#xD;
      loss of bone in participants legs due to SCI. This drug is FDA approved to treat osteoporosis&#xD;
      in women after menopause who have an increased risk for fractures, to treat women receiving&#xD;
      certain treatments for breast cancer who have an increased risk of fractures, and to treat&#xD;
      bone loss in men receiving certain treatments for prostate cancer who have increased risk for&#xD;
      fractures. This drug is considered experimental for the purpose of this study. Study&#xD;
      participation will last for approximately 12 months (6 study visits total), visits will range&#xD;
      from1-4.5 hours depending on the number of tests that need to be completed. The study is a&#xD;
      double-blinded placebo trail in which the participant will be randomly assigned to on of two&#xD;
      groups, Denosumab injections or placebo - inactive salt solution injections.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of this study is to test the efficacy of a potent anti-resorptive&#xD;
      agent, denosumab [receptor activator of nuclear factor-κB ligand (RANKL) antibody; Amgen&#xD;
      Inc.] to preserve bone mass at the hip and knee and trabecular connectivity at the knee after&#xD;
      subacute motor-incomplete SCI [American Spinal Injury Association (AIS) neurological&#xD;
      classification scale C and D] at the James J. Peters VA Medical Center (JJPVAMC) and Kessler&#xD;
      Institute for Rehabilitation (KIR). A randomized, double-blind, placebo-controlled, parallel&#xD;
      group trial will be performed in thirty-two subjects with acute, motor-incomplete SCI (≤6&#xD;
      months) who have been admitted to JJPVAMC or the KIR. Denosumab (60 mg SC) will be&#xD;
      administered at baseline, 6, and 12 months; the placebo group will receive normal saline&#xD;
      subcutaneously. Denosumab will be administered as soon as possible, but up to 24 weeks, after&#xD;
      SCI. The last dose of denosumab and placebo will be administered at 6 months, with the&#xD;
      anticipated effect of the drug to persist and inhibit bone resorption at least until the 12&#xD;
      month time point.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 1, 2017</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>areal bone mineral density (aBMD) by dual energy X-ray absorptiometry (DXA)</measure>
    <time_frame>Prior to denosumab or placebo administration and 18 months after denosumab or placebo administration</time_frame>
    <description>Efficacy of denosumab to prevent aBMD loss at the distal femur and proximal tibia</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>volumetric BMD (vBMD) and microarchitecture by peripheral quantitative computed tomography</measure>
    <time_frame>Prior to denosumab or placebo administration and 12 months after denosumab or placebo administration</time_frame>
    <description>Efficacy of denosumab to prevent vBMD loss and microarchitecture deterioration at the distal femur and proximal tibia</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">32</enrollment>
  <condition>Secondary Osteoporosis</condition>
  <condition>Spinal Cord Injury</condition>
  <arm_group>
    <arm_group_label>Denosumab, AIS Grade C (non-ambulatory)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>8 subjects with AIS grade C will be randomized to receive Denosumab (Prolia 120mg SC) administered at baseline and 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo, AIS Grade C (non-ambulatory)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>8 subjects with AIS grade C will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Denosumab, AIS Grade D (ambulatory)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>8 subjects with AIS grade D will be randomized to receive Denosumab (Prolia 120mg SC) administered at baseline and 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo, AIS Grade D (ambulatory)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>8 subjects with AIS grade D will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Denosumab (Prolia)</intervention_name>
    <description>In clinical trials, denosumab (Amgen Inc., Thousand Oaks, CA), has been shown to be more potent in reducing osteoclastosis and function than bisphosphonates. The dose of denosumab chosen for our protocol in patients after acute SCI will be the same dose that has been shown to be efficacious to treat postmenopausal osteoporosis (60 mg SQ q 6 months).</description>
    <arm_group_label>Denosumab, AIS Grade C (non-ambulatory)</arm_group_label>
    <arm_group_label>Denosumab, AIS Grade D (ambulatory)</arm_group_label>
    <other_name>Xgeva</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo (normal saline)</intervention_name>
    <description>Identical Denosumab volume of normal saline</description>
    <arm_group_label>Placebo, AIS Grade C (non-ambulatory)</arm_group_label>
    <arm_group_label>Placebo, AIS Grade D (ambulatory)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Motor incomplete SCI [American Spinal Injury Association Impairment Scale (AIS) grades&#xD;
             C and D];&#xD;
&#xD;
          2. Duration of injury &lt; 6-months; and&#xD;
&#xD;
          3. Males between the ages of 18 and 65 years old and females between the ages of 18 and&#xD;
             50 years old.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Extensive life-threatening injuries in addition to SCI;&#xD;
&#xD;
          2. Acute fracture or extensive bone trauma;&#xD;
&#xD;
          3. History of prior bone disease (Paget's hyperparathyroidism, osteoporosis, etc.)&#xD;
&#xD;
          4. Post-menopausal women;&#xD;
&#xD;
          5. Men with known hypogonadism prior to SCI;&#xD;
&#xD;
          6. Anabolic or Steroid hormonal therapy; within the past year and longer than six months;&#xD;
&#xD;
          7. Hyperthyroidism;&#xD;
&#xD;
          8. Cushing's disease or syndrome;&#xD;
&#xD;
          9. Severe underlying chronic disease;&#xD;
&#xD;
         10. History of chronic alcohol abuse;&#xD;
&#xD;
         11. Diagnosis of Hypocalcemia;&#xD;
&#xD;
         12. Pregnancy;&#xD;
&#xD;
         13. Existing dental condition/dental infection;&#xD;
&#xD;
         14. Diagnosis of heterotopic ossification at the hip and/or knee region and receiving a&#xD;
             bisphosphonates [e.g. alendronate sodium (Fosamax) or etidronate disodium (Didronel)]&#xD;
             that will no longer make participants eligible to receive the study medication/placebo&#xD;
             but are still eligible to complete follow-up outcome measures as described in the work&#xD;
             schedule;&#xD;
&#xD;
         15. Current diagnosis of cancer or history of cancer; and&#xD;
&#xD;
         16. Any patient receiving moderate or high dose corticosteroids (&gt;40 mg/d prednisone or an&#xD;
             equivalent dose of other corticosteroid) for longer than one week, not including drug&#xD;
             administered in an attempt to preserve neurological function at the time of acute SCI.&#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>William A Bauman, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>James J. Peters VA Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Steven C Kirshblum, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kessler Institute for Rehabilitation</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Christopher M Cirnigliaro, M.S.</last_name>
    <phone>973-731-3900</phone>
    <phone_ext>2755</phone_ext>
    <email>christopher.cirnigliaro@va.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>William A Bauman, M.D.</last_name>
    <phone>718-584-9000</phone>
    <phone_ext>5428</phone_ext>
    <email>william.bauman@va.gov</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Kessler Institute for Rehabilitation</name>
      <address>
        <city>West Orange</city>
        <state>New Jersey</state>
        <zip>07052</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Christopher M Cirnigliaro, M.S.</last_name>
      <phone>973-731-3900</phone>
      <phone_ext>2755</phone_ext>
      <email>christopher.cirnigliaro@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Steven C Kirshblum, M.D.</last_name>
      <phone>973-731-3900</phone>
      <phone_ext>2258</phone_ext>
      <email>skirshblum@kessler-rehab.com</email>
    </contact_backup>
    <investigator>
      <last_name>Christopher M Cirniliaro, M.S.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Steven C Kirshblum, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>James J. Peters VA Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10468</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joshua C Hobson, M.S.</last_name>
      <phone>718-584-9000</phone>
      <phone_ext>3129</phone_ext>
      <email>joshua.hobson@va.gov</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Gifre L, Vidal J, Carrasco JL, Muxi A, Portell E, Monegal A, Guanabens N, Peris P. Denosumab increases sublesional bone mass in osteoporotic individuals with recent spinal cord injury. Osteoporos Int. 2016 Jan;27(1):405-10. doi: 10.1007/s00198-015-3333-5. Epub 2015 Sep 30.</citation>
    <PMID>26423406</PMID>
  </reference>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <last_update_submitted>March 6, 2019</last_update_submitted>
  <last_update_submitted_qc>March 6, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>James J. Peters Veterans Affairs Medical Center</investigator_affiliation>
    <investigator_full_name>William A. Bauman, M.D.</investigator_full_name>
    <investigator_title>Director, Clinical Investigator, National Center of Excellence for the Medical Consequences of Spinal Cord Injury</investigator_title>
  </responsible_party>
  <keyword>Spinal Cord Injury</keyword>
  <keyword>Denosumab</keyword>
  <keyword>Osteoporosis</keyword>
  <keyword>Dual Energy X-ray Absorptiometry</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoporosis</mesh_term>
    <mesh_term>Spinal Cord Injuries</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Denosumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>An IPD is not desired by the investigators and is not part of the regulatory guidelines at the participating institutions</ipd_description>
  </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/NCT03029442
org study id: BAU-16-057
nct id: NCT03029442
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine the usefulness of a drug, denosumab, to prevent the
      loss of bone in participants legs due to SCI. This drug is FDA approved to treat osteoporosis
      in women after menopause who have an increased risk for fractures, to treat women receiving
      certain treatments for breast cancer who have an increased risk of fractures, and to treat
      bone loss in men receiving certain treatments for prostate cancer who have increased risk for
      fractures. This drug is considered experimental for the purpose of this study. Study
      participation will last for approximately 12 months (6 study visits total), visits will range
      from1-4.5 hours depending on the number of tests that need to be completed. The study is a
      double-blinded placebo trail in which the participant will be randomly assigned to on of two
      groups, Denosumab injections or placebo - inactive salt solution injections.
The primary objective of this study is to test the efficacy of a potent anti-resorptive
      agent, denosumab [receptor activator of nuclear factor-κB ligand (RANKL) antibody; Amgen
      Inc.] to preserve bone mass at the hip and knee and trabecular connectivity at the knee after
      subacute motor-incomplete SCI [American Spinal Injury Association (AIS) neurological
      classification scale C and D] at the James J. Peters VA Medical Center (JJPVAMC) and Kessler
      Institute for Rehabilitation (KIR). A randomized, double-blind, placebo-controlled, parallel
      group trial will be performed in thirty-two subjects with acute, motor-incomplete SCI (≤6
      months) who have been admitted to JJPVAMC or the KIR. Denosumab (60 mg SC) will be
      administered at baseline, 6, and 12 months; the placebo group will receive normal saline
      subcutaneously. Denosumab will be administered as soon as possible, but up to 24 weeks, after
      SCI. The last dose of denosumab and placebo will be administered at 6 months, with the
      anticipated effect of the drug to persist and inhibit bone resorption at least until the 12
      month time point.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: areal bone mineral density (aBMD) by dual energy X-ray absorptiometry (DXA)
time frame: Prior to denosumab or placebo administration and 18 months after denosumab or placebo administration
description: Efficacy of denosumab to prevent aBMD loss at the distal femur and proximal tibia
measure: volumetric BMD (vBMD) and microarchitecture by peripheral quantitative computed tomography
time frame: Prior to denosumab or placebo administration and 12 months after denosumab or placebo administration
description: Efficacy of denosumab to prevent vBMD loss and microarchitecture deterioration at the distal femur and proximal tibia
arm group label: Denosumab, AIS Grade C (non-ambulatory)
arm group type: Experimental
description: 8 subjects with AIS grade C will be randomized to receive Denosumab (Prolia 120mg SC) administered at baseline and 6 months.
arm group label: Placebo, AIS Grade C (non-ambulatory)
arm group type: Placebo Comparator
description: 8 subjects with AIS grade C will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points.
arm group label: Denosumab, AIS Grade D (ambulatory)
arm group type: Experimental
description: 8 subjects with AIS grade D will be randomized to receive Denosumab (Prolia 120mg SC) administered at baseline and 6 months.
arm group label: Placebo, AIS Grade D (ambulatory)
arm group type: Placebo Comparator
description: 8 subjects with AIS grade D will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points.
intervention type: Drug
intervention name: Denosumab (Prolia)
description: In clinical trials, denosumab (Amgen Inc., Thousand Oaks, CA), has been shown to be more potent in reducing osteoclastosis and function than bisphosphonates. The dose of denosumab chosen for our protocol in patients after acute SCI will be the same dose that has been shown to be efficacious to treat postmenopausal osteoporosis (60 mg SQ q 6 months).
arm group label: Denosumab, AIS Grade C (non-ambulatory)
arm group label: Denosumab, AIS Grade D (ambulatory)
other name: Xgeva
intervention type: Other
intervention name: Placebo (normal saline)
description: Identical Denosumab volume of normal saline
arm group label: Placebo, AIS Grade C (non-ambulatory)
arm group label: Placebo, AIS Grade D (ambulatory)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: William A Bauman, M.D.
role: Principal Investigator
affiliation: James J. Peters VA Medical Center
last name: Steven C Kirshblum, M.D.
role: Principal Investigator
affiliation: Kessler Institute for Rehabilitation
last name: Christopher M Cirnigliaro, M.S.
phone: 973-731-3900
phone ext: 2755
email: christopher.cirnigliaro@va.gov
last name: William A Bauman, M.D.
phone: 718-584-9000
phone ext: 5428
email: william.bauman@va.gov
facility: 
status: Not yet recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
country: United States
citation: Gifre L, Vidal J, Carrasco JL, Muxi A, Portell E, Monegal A, Guanabens N, Peris P. Denosumab increases sublesional bone mass in osteoporotic individuals with recent spinal cord injury. Osteoporos Int. 2016 Jan;27(1):405-10. doi: 10.1007/s00198-015-3333-5. Epub 2015 Sep 30.
PMID: 26423406
responsible party type: Principal Investigator
investigator affiliation: James J. Peters Veterans Affairs Medical Center
investigator full name: William A. Bauman, M.D.
investigator title: Director, Clinical Investigator, National Center of Excellence for the Medical Consequences of Spinal Cord Injury
mesh term: Osteoporosis
mesh term: Spinal Cord Injuries
mesh term: Wounds and Injuries
mesh term: Denosumab
sharing ipd: No
ipd description: An IPD is not desired by the investigators and is not part of the regulatory guidelines at the participating institutions