<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/NCT02975518</url>
  </required_header>
  <id_info>
    <org_study_id>Protocol v 3</org_study_id>
    <nct_id>NCT02975518</nct_id>
  </id_info>
  <brief_title>Tracking Endothelial Cells in Arterial Injury</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Edinburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>British Heart Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Edinburgh</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      We plan to track the migratory behaviour of culture-expanded enothelial outgrowth cells in&#xD;
      the context of vascular injury sustained during elective coronary angiography.&#xD;
&#xD;
      We will use Flouro-deoxyglucose-labelling and PET-CT to track the endothelial cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The radial artery is commonly injured following trans-radial cardiac catheterisation and this&#xD;
      injury can be demonstrated as a reduction in endothelial function as measured by&#xD;
      flow-mediated dilatation which recovers with time (13-15). Thus the radial artery is useful&#xD;
      as a model of mechanical arterial injury as radial artery trauma is common and endothelial&#xD;
      function can be followed longitudinally with a non-invasive test.&#xD;
&#xD;
      Endothelial progenitor cells localise to sites of arterial injury in animal models both in&#xD;
      vitro and in vivo and accelerate re-endothelialisation as well as attenuating neointimal&#xD;
      hyperplasia (16-18), This has however not been demonstrated in man.&#xD;
&#xD;
      Our research group, in collaboration with the Scottish Blood Transfusion Service (SNBTS) have&#xD;
      developed a good manufacturing practice (GMP)-compliant process for manufacturing an&#xD;
      endothelial progenitor cell (EPC) product (SNBTS will manufacture the final product&#xD;
      administered to patients). We have also demonstrated in vitro that we can label these cells&#xD;
      with the radioisotope 18 F-fluorodeoxyglucose (18F-FDG) and that activity can be detected in&#xD;
      as few as 200 cells using a hybrid positron emission and computed tomography (PET-CT) scanner&#xD;
      (Biograph mCT Siemens Medical Systems, Erlangen, Germany). We will therefore be able to track&#xD;
      the fate of these cells in vivo. The major potential advantage of imaging in this way is that&#xD;
      only 18F-FDG associated with EPCs will be delivered to the patient, removing the issue of&#xD;
      background attenuation due to &quot;free&quot; circulating 18F-FDG. A similar technique has previously&#xD;
      been employed in vivo to track homing of unselected autologous bone marrow cells to infarcted&#xD;
      myocardium(19). Following intracoronary delivery using this technique, the authors were able&#xD;
      to detect 1.3% - 2.6% of 18F-FDG-labelled cells in the infarcted myocardium. Demonstrating&#xD;
      that EPCs are able to home to and integrate at sites of vascular injury in man is a critical&#xD;
      step in understanding the role of EPCs in vascular repair&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2015</start_date>
  <completion_date type="Actual">March 12, 2018</completion_date>
  <primary_completion_date type="Actual">March 12, 2018</primary_completion_date>
  <phase>N/A</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Standard uptake value</measure>
    <time_frame>0-4 hours</time_frame>
    <description>Standard-uptake values of injured sections of artery will be compared to remote uninjured artery</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">36</enrollment>
  <condition>Endothelial Progenitor Cells</condition>
  <condition>Coronary Artery Disease</condition>
  <condition>Vascular Injury</condition>
  <condition>Coronary Angiography</condition>
  <arm_group>
    <arm_group_label>Intra-venous infusion of Flourodeoxyglucose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>As a control for radio labelled cells, Flourodeoxyglucose will be administered intra-venously at an activity equal to that injected with the labelled endothelial cells.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intra-Arterial infusion of Flourodeoxyglucose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>As a control for radio labelled cells, Flourodeoxyglucose will be administered intra-arterially at an activity equal to that injected with the labelled endothelial cells.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intra-venous injection of radio-labelled endothelial cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Endothelial cells labelled with flourodeoxyglucose will be injected intra-venously with their distribution tracked using PET CT.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intra-Arterial injection of radio-labelled endothelial cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Endothelial cells labelled with flourodeoxyglucose will be injected intra-arterially with their distribution tracked using PET CT.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Administration of radio labelled endothelial outgrowth cells</intervention_name>
    <description>Radio labelled endothelial outgrowth cells will be administered to patients undergoing elective coronary angiography and stenting. They will be administered intra-venously and intra-arterially (right radial artery) in separate arms. Migratory behaviour of these cells will be defined using PET CT. Intra-venous and intra-arterial injection of free radio tracer will serve as a control comparator arms.</description>
    <arm_group_label>Intra-Arterial infusion of Flourodeoxyglucose</arm_group_label>
    <arm_group_label>Intra-Arterial injection of radio-labelled endothelial cells</arm_group_label>
    <arm_group_label>Intra-venous infusion of Flourodeoxyglucose</arm_group_label>
    <arm_group_label>Intra-venous injection of radio-labelled endothelial cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Undergoing coronary angiography for known or suspected ischaemic heart disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous coronary artery bypass surgery.&#xD;
&#xD;
          2. Planned angiography via the femoral artery as a sole arterial access route&#xD;
&#xD;
          3. Anaemia &lt;10g/L&#xD;
&#xD;
          4. Severe valvular heart disease&#xD;
&#xD;
          5. Acute myocardial infarction within previous three months&#xD;
&#xD;
          6. Cardiac failure (Killip class ≥II).&#xD;
&#xD;
          7. Insulin dependent diabetes mellitus&#xD;
&#xD;
          8. Hepatic failure (Childs-Pugh grades B or C).&#xD;
&#xD;
          9. Renal failure (estimated glomerular filtration rate &lt;25 mL/min).&#xD;
&#xD;
         10. Intercurrent illness including patients with a systemic inflammatory disorder or&#xD;
             underlying malignancy.&#xD;
&#xD;
         11. Women of child-bearing age not ensuring reliable methods of contraception.&#xD;
&#xD;
         12. Inability to provide informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Edinburgh</name>
      <address>
        <city>Edinburgh</city>
        <state>Midlothian</state>
        <zip>EH74DL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>November 23, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>July 15, 2021</last_update_submitted>
  <last_update_submitted_qc>July 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Vascular System Injuries</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/NCT02975518
org study id: Protocol v 3
nct id: NCT02975518
lead sponsor: 
collaborator: 
has dmc: No
We plan to track the migratory behaviour of culture-expanded enothelial outgrowth cells in
      the context of vascular injury sustained during elective coronary angiography.

      We will use Flouro-deoxyglucose-labelling and PET-CT to track the endothelial cells.
The radial artery is commonly injured following trans-radial cardiac catheterisation and this
      injury can be demonstrated as a reduction in endothelial function as measured by
      flow-mediated dilatation which recovers with time (13-15). Thus the radial artery is useful
      as a model of mechanical arterial injury as radial artery trauma is common and endothelial
      function can be followed longitudinally with a non-invasive test.

      Endothelial progenitor cells localise to sites of arterial injury in animal models both in
      vitro and in vivo and accelerate re-endothelialisation as well as attenuating neointimal
      hyperplasia (16-18), This has however not been demonstrated in man.

      Our research group, in collaboration with the Scottish Blood Transfusion Service (SNBTS) have
      developed a good manufacturing practice (GMP)-compliant process for manufacturing an
      endothelial progenitor cell (EPC) product (SNBTS will manufacture the final product
      administered to patients). We have also demonstrated in vitro that we can label these cells
      with the radioisotope 18 F-fluorodeoxyglucose (18F-FDG) and that activity can be detected in
      as few as 200 cells using a hybrid positron emission and computed tomography (PET-CT) scanner
      (Biograph mCT Siemens Medical Systems, Erlangen, Germany). We will therefore be able to track
      the fate of these cells in vivo. The major potential advantage of imaging in this way is that
      only 18F-FDG associated with EPCs will be delivered to the patient, removing the issue of
      background attenuation due to "free" circulating 18F-FDG. A similar technique has previously
      been employed in vivo to track homing of unselected autologous bone marrow cells to infarcted
      myocardium(19). Following intracoronary delivery using this technique, the authors were able
      to detect 1.3% - 2.6% of 18F-FDG-labelled cells in the infarcted myocardium. Demonstrating
      that EPCs are able to home to and integrate at sites of vascular injury in man is a critical
      step in understanding the role of EPCs in vascular repair
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Standard uptake value
time frame: 0-4 hours
description: Standard-uptake values of injured sections of artery will be compared to remote uninjured artery
arm group label: Intra-venous infusion of Flourodeoxyglucose
arm group type: Active Comparator
description: As a control for radio labelled cells, Flourodeoxyglucose will be administered intra-venously at an activity equal to that injected with the labelled endothelial cells.
arm group label: Intra-Arterial infusion of Flourodeoxyglucose
arm group type: Active Comparator
description: As a control for radio labelled cells, Flourodeoxyglucose will be administered intra-arterially at an activity equal to that injected with the labelled endothelial cells.
arm group label: Intra-venous injection of radio-labelled endothelial cells
arm group type: Experimental
description: Endothelial cells labelled with flourodeoxyglucose will be injected intra-venously with their distribution tracked using PET CT.
arm group label: Intra-Arterial injection of radio-labelled endothelial cells
arm group type: Experimental
description: Endothelial cells labelled with flourodeoxyglucose will be injected intra-arterially with their distribution tracked using PET CT.
intervention type: Biological
intervention name: Administration of radio labelled endothelial outgrowth cells
description: Radio labelled endothelial outgrowth cells will be administered to patients undergoing elective coronary angiography and stenting. They will be administered intra-venously and intra-arterially (right radial artery) in separate arms. Migratory behaviour of these cells will be defined using PET CT. Intra-venous and intra-arterial injection of free radio tracer will serve as a control comparator arms.
arm group label: Intra-Arterial infusion of Flourodeoxyglucose
arm group label: Intra-Arterial injection of radio-labelled endothelial cells
arm group label: Intra-venous infusion of Flourodeoxyglucose
arm group label: Intra-venous injection of radio-labelled endothelial cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Vascular System Injuries