<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/NCT03307876</url>
  </required_header>
  <id_info>
    <org_study_id>201601</org_study_id>
    <nct_id>NCT03307876</nct_id>
  </id_info>
  <brief_title>Injection of an Autologous A2M Concentrate Alleviates Back Pain in FAC-positive Patients</brief_title>
  <official_title>Intradiscal Injection of an Autologous Alpha-2-macroglobulin (A2M) Concentrate Alleviates Back Pain in FAC-positive Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Scuderi, Gaetano J., M.D.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Scuderi, Gaetano J., M.D.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A cartilage degradation product, the Fibronectin-Aggrecan complex (FAC), has been identified&#xD;
      in patients with degenerative disc disease (DDD). Alpha-2-macroglobulin (A2M) can prevent the&#xD;
      formation of the G3 domain of aggrecan, reducing the fibronectin-aggrecan G3 complex and&#xD;
      therefore may be an efficacious treatment. The present study was designed to determine 1) the&#xD;
      ability of autologous concentrated A2M to relieve back pain in patients with LBP from DDD and&#xD;
      2) the ability of FAC to predict the response to this biologic therapy.&#xD;
&#xD;
      24 patients with low back pain and MRI-concordant DDD had prospective evaluation. Oswestry&#xD;
      disability index (ODI) and visual analog scores (VAS) were noted at baseline and at 3- and&#xD;
      6-month follow-up. Primary outcome of clinical improvement was defined as patients with both&#xD;
      a decrease in VAS of at least 3 points and ODI &gt;20 points. Molecular discography and delayed&#xD;
      FAC analysis and injection of platelet poor plasma at the time of the procedure. Patients&#xD;
      with FACT-positive assays were significantly more likely to show improvement in their VAS and&#xD;
      ODI at follow-up.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives: A cartilage degradation product, the Fibronectin-Aggrecan complex (FAC), has been&#xD;
      identified in patients with degenerative disc disease (DDD). Alpha-2-macroglobulin (A2M) can&#xD;
      prevent the formation of the G3 domain of aggrecan, reducing the fibronectin-aggrecan G3&#xD;
      complex and therefore may be an efficacious treatment. The present study was designed to&#xD;
      determine 1) the ability of autologous platelet poor plasma (PPP) with concentrated A2M to&#xD;
      relieve back pain in patients with low back pain (LBP) from DDD and 2) the ability of FAC to&#xD;
      predict the response to this biologic therapy.&#xD;
&#xD;
      Study design/setting: Prospective cohort&#xD;
&#xD;
      Patients: 24 patients with low back pain and MRI-concordant DDD&#xD;
&#xD;
      Methods: All patients underwent lavage for molecular discography and delayed FAC analysis and&#xD;
      injection of autologous platelet poor plasma (PPP) rich in A2M (Cytonics Autologous Protease&#xD;
      Inhibitor Concentrate, APIC) at the time of the procedure. ANOVA with Bonferonni correction&#xD;
      for multiple comparisons was performed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">May 2015</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>Oswestry Disability Index (ODI)</measure>
    <time_frame>3 and 6 months</time_frame>
    <description>Change from Baseline ODI at 3 and 6 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Visual Analogue Score (VAS)</measure>
    <time_frame>3 and 6 month</time_frame>
    <description>Change from Baseline VAS at 3 and 6 months</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">24</enrollment>
  <condition>Low Back Pain</condition>
  <arm_group>
    <arm_group_label>groups that are fac + and -</arm_group_label>
    <description>autologous PPP injection is given to all patients. Prior to injection, a lavage of the disc space is taken to test for FAC.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>autologous PPP injection</intervention_name>
    <description>autologous platelet poor plasma (PPP) injection taken from the participants own blood is injected in to all patients.</description>
    <arm_group_label>groups that are fac + and -</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      lavage sample of the disc for FAC analysis is taken prior to autologous PPP injection. It was&#xD;
      discarded after the analysis was complete.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Adult patients with LBP&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 years of age or greater with a history of low back pain complaints primarily&#xD;
             dictated by pain with associated sensory symptoms and/or low back pain for 6 months or&#xD;
             more who had failed expectant management with NSAIDS, activity modification, and/or&#xD;
             physical therapy.&#xD;
&#xD;
          -  MRI that demonstrated signs of degenerative disc disease at one or more levels with a&#xD;
             Pfirrmann grade of II to IV.&#xD;
&#xD;
          -  Age from 18 to 65 with axial back pain of at least 6 months duration.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a history of oral or injected corticosteroid medication within a three&#xD;
             month period prior to disc injection.&#xD;
&#xD;
          -  Chronic medical conditions associated with metabolic or inflammatory disorders&#xD;
             (insulin-dependent diabetes mellitus, severe coronary artery disease, rheumatic or&#xD;
             autoimmune diseases) were excluded from the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>June 24, 2016</study_first_submitted>
  <study_first_submitted_qc>October 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 12, 2017</study_first_posted>
  <last_update_submitted>October 11, 2017</last_update_submitted>
  <last_update_submitted_qc>October 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>biologic,</keyword>
  <keyword>Alpha 2 Macroglobulin</keyword>
  <keyword>A2M</keyword>
  <keyword>back pain</keyword>
  <keyword>APIC</keyword>
  <keyword>FAC</keyword>
  <keyword>FACT</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Back Pain</mesh_term>
    <mesh_term>Low Back Pain</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/NCT03307876
org study id: 201601
nct id: NCT03307876
lead sponsor: 
has dmc: No
A cartilage degradation product, the Fibronectin-Aggrecan complex (FAC), has been identified
      in patients with degenerative disc disease (DDD). Alpha-2-macroglobulin (A2M) can prevent the
      formation of the G3 domain of aggrecan, reducing the fibronectin-aggrecan G3 complex and
      therefore may be an efficacious treatment. The present study was designed to determine 1) the
      ability of autologous concentrated A2M to relieve back pain in patients with LBP from DDD and
      2) the ability of FAC to predict the response to this biologic therapy.

      24 patients with low back pain and MRI-concordant DDD had prospective evaluation. Oswestry
      disability index (ODI) and visual analog scores (VAS) were noted at baseline and at 3- and
      6-month follow-up. Primary outcome of clinical improvement was defined as patients with both
      a decrease in VAS of at least 3 points and ODI >20 points. Molecular discography and delayed
      FAC analysis and injection of platelet poor plasma at the time of the procedure. Patients
      with FACT-positive assays were significantly more likely to show improvement in their VAS and
      ODI at follow-up.
Objectives: A cartilage degradation product, the Fibronectin-Aggrecan complex (FAC), has been
      identified in patients with degenerative disc disease (DDD). Alpha-2-macroglobulin (A2M) can
      prevent the formation of the G3 domain of aggrecan, reducing the fibronectin-aggrecan G3
      complex and therefore may be an efficacious treatment. The present study was designed to
      determine 1) the ability of autologous platelet poor plasma (PPP) with concentrated A2M to
      relieve back pain in patients with low back pain (LBP) from DDD and 2) the ability of FAC to
      predict the response to this biologic therapy.

      Study design/setting: Prospective cohort

      Patients: 24 patients with low back pain and MRI-concordant DDD

      Methods: All patients underwent lavage for molecular discography and delayed FAC analysis and
      injection of autologous platelet poor plasma (PPP) rich in A2M (Cytonics Autologous Protease
      Inhibitor Concentrate, APIC) at the time of the procedure. ANOVA with Bonferonni correction
      for multiple comparisons was performed.
observational model: Case-Control
time perspective: Prospective
measure: Oswestry Disability Index (ODI)
time frame: 3 and 6 months
description: Change from Baseline ODI at 3 and 6 months
measure: Visual Analogue Score (VAS)
time frame: 3 and 6 month
description: Change from Baseline VAS at 3 and 6 months
arm group label: groups that are fac + and -
description: autologous PPP injection is given to all patients. Prior to injection, a lavage of the disc space is taken to test for FAC.
intervention type: Other
intervention name: autologous PPP injection
description: autologous platelet poor plasma (PPP) injection taken from the participants own blood is injected in to all patients.
arm group label: groups that are fac + and -
lavage sample of the disc for FAC analysis is taken prior to autologous PPP injection. It was
      discarded after the analysis was complete.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
responsible party type: Sponsor
mesh term: Back Pain
mesh term: Low Back Pain
sharing ipd: No