<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/NCT02259257</url>
  </required_header>
  <id_info>
    <org_study_id>226-14 RMB CTIL</org_study_id>
    <nct_id>NCT02259257</nct_id>
  </id_info>
  <brief_title>3D/4D Ultrasound Contrast Enhanced Imaging (CEUS) for Carotid Plaque Vulnerability</brief_title>
  <acronym>CEUS carotid</acronym>
  <official_title>3D/4D Ultrasound Contrast Enhanced Imaging (CEUS) for Carotid Plaque Vulnerability</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Diana Gaitini MD.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Technion, Israel Institute of Technology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rush University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Rambam Health Care Campus</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Contrast enhanced 3D/4D (3 dimension/4 dimension) ultrasound (CEUS) provides visualization of&#xD;
      the dynamic vascular features of the plaques, in a unique spatial format using three&#xD;
      orthogonal planes and angiogram-like images. Therefore, the observer can utilize the entire&#xD;
      vascular system in a volumetric manner (3D). The rotation of the intra-plaque neovasculature&#xD;
      as viewed in various angles provides a realistic representation that is more easily&#xD;
      appreciated. Inter-observer variability for individual plaques has been assessed and&#xD;
      inter-observer variability and inter-scan variability (the analysis of multiple images from&#xD;
      single patients in longitudinal studies) were dependent on plaque size, with larger plaques&#xD;
      showing lower variability. Therefore, the proposed 3D/4D vs. 2D CEUS imaging of the carotid&#xD;
      plaque will provide added value for the depiction of the and quantification of intra-plaque&#xD;
      blood vessel density by providing a true volumetric viewing area. This data will be&#xD;
      correlated to the subsequent surgical specimens. The goal of the protocol is to investigate&#xD;
      the correlation of intra-plaque blood vessel density and hemorrhage to 3D/4D CEUS vasa&#xD;
      vasorum using quantitative software analyses. The histology methods used for quantification&#xD;
      of hemorrhage and vessel density analyses.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>November 2014</start_date>
  <completion_date type="Anticipated">November 2017</completion_date>
  <primary_completion_date type="Anticipated">November 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Carotid plaque vascularization as seen on CEUS and histology compared to 3 year follow up of cardiovascular events.</measure>
    <time_frame>Post processing of CEUS will be done up to 3 years post surgery</time_frame>
    <description>Post processing of CEUS data for carotid plaque vascularization.&#xD;
In addition all carotid artery histology specimens, routinely obtained at the time of surgery at each center, will be analyzed to include the following tissue stains: CD3, CD31, CD38 and Hemosiderin.</description>
  </primary_outcome>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Atherosclerosis</condition>
  <condition>Stroke</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Tissue: Carotid plaque histological specimen&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients scheduled for endarterectomy due to carotid stenosis demonstrated on a previous&#xD;
        imaging examination (exhibiting &gt;50% intra-luminal narrowing or a maximum IMT measurement&#xD;
        of &gt; 1.5mm) or have experienced a CVA event (TIA/CVA) .&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult subjects with known carotid artery disease will be included.&#xD;
&#xD;
          -  Subject must be able and willing to comply with study procedures and provide a signed&#xD;
             and dated informed consent including consent for 3 year annual follow up.&#xD;
&#xD;
          -  Subjects will be screened by asking each study subject if they have known or suspected&#xD;
             hypersensitivity to any of the components of Optison, blood, blood products of&#xD;
             albumin. In addition, each study subject will be asked if they have a right to left or&#xD;
             bi-directional or transient right to left cardiac shunts. If any of the above&#xD;
             questions are answered in the positive, the patient will not be eligible for inclusion&#xD;
             in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female subjects of child bearing potential will be excluded.&#xD;
&#xD;
          -  The subject presents any clinically active, serious, life-threatening disease, with a&#xD;
             life expectancy of less than 1 month or where study participation may compromise the&#xD;
             management of the subject or other reason that in the judgment of the investigator&#xD;
             makes the subject unsuitable for participation in the study.&#xD;
&#xD;
          -  History of acute occlusion requiring medical intervention of any artery (including&#xD;
             aorta) within 6 months of consent.&#xD;
&#xD;
          -  Has a known or suspected hypersensitivity to any of the components of Optison, blood,&#xD;
             blood products, or albumin.&#xD;
&#xD;
          -  Has known right to left, bi-directional or transient right to left cardiac shunts.&#xD;
&#xD;
          -  Any known contra-indications as listed on the current Optison package insert.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Steven B Feinstein, MD</last_name>
    <phone>1-312-942-5000</phone>
    <email>Steven_Feinstein@rush.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Diana E Gaitini, MD</last_name>
    <phone>972-4-8542664</phone>
    <email>d_gaitini@rambam.health.gov.il</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Rambam Health Care Center</name>
      <address>
        <city>Haifa</city>
        <zip>31096</zip>
        <country>Israel</country>
      </address>
    </facility>
    <investigator>
      <last_name>Dan Adam, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Eyal Bercovich, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <reference>
    <citation>Hoogi A, Adam D, Hoffman A, Kerner H, Reisner S, Gaitini D. Carotid plaque vulnerability: quantification of neovascularization on contrast-enhanced ultrasound with histopathologic correlation. AJR Am J Roentgenol. 2011 Feb;196(2):431-6. doi: 10.2214/AJR.10.4522.</citation>
    <PMID>21257897</PMID>
  </reference>
  <reference>
    <citation>Staub D, Schinkel AF, Coll B, Coli S, van der Steen AF, Reed JD, Krueger C, Thomenius KE, Adam D, Sijbrands EJ, ten Cate FJ, Feinstein SB. Contrast-enhanced ultrasound imaging of the vasa vasorum: from early atherosclerosis to the identification of unstable plaques. JACC Cardiovasc Imaging. 2010 Jul;3(7):761-71. doi: 10.1016/j.jcmg.2010.02.007.</citation>
    <PMID>20633855</PMID>
  </reference>
  <reference>
    <citation>Michel JB, Virmani R, Arbustini E, Pasterkamp G. Intraplaque haemorrhages as the trigger of plaque vulnerability. Eur Heart J. 2011 Aug;32(16):1977-85, 1985a, 1985b, 1985c. doi: 10.1093/eurheartj/ehr054. Epub 2011 Mar 12.</citation>
    <PMID>21398643</PMID>
  </reference>
  <reference>
    <citation>Hellings WE, Peeters W, Moll FL, Piers SR, van Setten J, Van der Spek PJ, de Vries JP, Seldenrijk KA, De Bruin PC, Vink A, Velema E, de Kleijn DP, Pasterkamp G. Composition of carotid atherosclerotic plaque is associated with cardiovascular outcome: a prognostic study. Circulation. 2010 May 4;121(17):1941-50. doi: 10.1161/CIRCULATIONAHA.109.887497. Epub 2010 Apr 19.</citation>
    <PMID>20404256</PMID>
  </reference>
  <reference>
    <citation>Sluimer JC, Daemen MJ. Novel concepts in atherogenesis: angiogenesis and hypoxia in atherosclerosis. J Pathol. 2009 May;218(1):7-29. doi: 10.1002/path.2518.</citation>
    <PMID>19309025</PMID>
  </reference>
  <reference>
    <citation>Shah F, Balan P, Weinberg M, Reddy V, Neems R, Feinstein M, Dainauskas J, Meyer P, Goldin M, Feinstein SB. Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis? Vasc Med. 2007 Nov;12(4):291-7. doi: 10.1177/1358863X07083363.</citation>
    <PMID>18048465</PMID>
  </reference>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>September 23, 2014</study_first_submitted>
  <study_first_submitted_qc>October 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2014</study_first_posted>
  <last_update_submitted>October 5, 2014</last_update_submitted>
  <last_update_submitted_qc>October 5, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 8, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Rambam Health Care Campus</investigator_affiliation>
    <investigator_full_name>Diana Gaitini MD.</investigator_full_name>
    <investigator_title>Director Ultrasound Unit, Dept of Medical Imaging</investigator_title>
  </responsible_party>
  <keyword>carotid arteriosclerosis</keyword>
  <keyword>contrast-enhanced ultrasound</keyword>
  <keyword>neovascularization</keyword>
  <keyword>quantitative analysis</keyword>
  <keyword>3D/4D imaging</keyword>
  <keyword>CEUS</keyword>
  <keyword>Vasa vasorum</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atherosclerosis</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/NCT02259257
org study id: 226-14 RMB CTIL
nct id: NCT02259257
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Contrast enhanced 3D/4D (3 dimension/4 dimension) ultrasound (CEUS) provides visualization of
      the dynamic vascular features of the plaques, in a unique spatial format using three
      orthogonal planes and angiogram-like images. Therefore, the observer can utilize the entire
      vascular system in a volumetric manner (3D). The rotation of the intra-plaque neovasculature
      as viewed in various angles provides a realistic representation that is more easily
      appreciated. Inter-observer variability for individual plaques has been assessed and
      inter-observer variability and inter-scan variability (the analysis of multiple images from
      single patients in longitudinal studies) were dependent on plaque size, with larger plaques
      showing lower variability. Therefore, the proposed 3D/4D vs. 2D CEUS imaging of the carotid
      plaque will provide added value for the depiction of the and quantification of intra-plaque
      blood vessel density by providing a true volumetric viewing area. This data will be
      correlated to the subsequent surgical specimens. The goal of the protocol is to investigate
      the correlation of intra-plaque blood vessel density and hemorrhage to 3D/4D CEUS vasa
      vasorum using quantitative software analyses. The histology methods used for quantification
      of hemorrhage and vessel density analyses.
observational model: Case-Only
time perspective: Prospective
measure: Carotid plaque vascularization as seen on CEUS and histology compared to 3 year follow up of cardiovascular events.
time frame: Post processing of CEUS will be done up to 3 years post surgery
description: Post processing of CEUS data for carotid plaque vascularization.
In addition all carotid artery histology specimens, routinely obtained at the time of surgery at each center, will be analyzed to include the following tissue stains: CD3, CD31, CD38 and Hemosiderin.
Tissue: Carotid plaque histological specimen
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Steven B Feinstein, MD
phone: 1-312-942-5000
email: Steven_Feinstein@rush.edu
last name: Diana E Gaitini, MD
phone: 972-4-8542664
email: d_gaitini@rambam.health.gov.il
facility: 
investigator: 
investigator: 
country: Israel
citation: Hoogi A, Adam D, Hoffman A, Kerner H, Reisner S, Gaitini D. Carotid plaque vulnerability: quantification of neovascularization on contrast-enhanced ultrasound with histopathologic correlation. AJR Am J Roentgenol. 2011 Feb;196(2):431-6. doi: 10.2214/AJR.10.4522.
PMID: 21257897
citation: Staub D, Schinkel AF, Coll B, Coli S, van der Steen AF, Reed JD, Krueger C, Thomenius KE, Adam D, Sijbrands EJ, ten Cate FJ, Feinstein SB. Contrast-enhanced ultrasound imaging of the vasa vasorum: from early atherosclerosis to the identification of unstable plaques. JACC Cardiovasc Imaging. 2010 Jul;3(7):761-71. doi: 10.1016/j.jcmg.2010.02.007.
PMID: 20633855
citation: Michel JB, Virmani R, Arbustini E, Pasterkamp G. Intraplaque haemorrhages as the trigger of plaque vulnerability. Eur Heart J. 2011 Aug;32(16):1977-85, 1985a, 1985b, 1985c. doi: 10.1093/eurheartj/ehr054. Epub 2011 Mar 12.
PMID: 21398643
citation: Hellings WE, Peeters W, Moll FL, Piers SR, van Setten J, Van der Spek PJ, de Vries JP, Seldenrijk KA, De Bruin PC, Vink A, Velema E, de Kleijn DP, Pasterkamp G. Composition of carotid atherosclerotic plaque is associated with cardiovascular outcome: a prognostic study. Circulation. 2010 May 4;121(17):1941-50. doi: 10.1161/CIRCULATIONAHA.109.887497. Epub 2010 Apr 19.
PMID: 20404256
citation: Sluimer JC, Daemen MJ. Novel concepts in atherogenesis: angiogenesis and hypoxia in atherosclerosis. J Pathol. 2009 May;218(1):7-29. doi: 10.1002/path.2518.
PMID: 19309025
citation: Shah F, Balan P, Weinberg M, Reddy V, Neems R, Feinstein M, Dainauskas J, Meyer P, Goldin M, Feinstein SB. Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis? Vasc Med. 2007 Nov;12(4):291-7. doi: 10.1177/1358863X07083363.
PMID: 18048465
responsible party type: Sponsor-Investigator
investigator affiliation: Rambam Health Care Campus
investigator full name: Diana Gaitini MD.
investigator title: Director Ultrasound Unit, Dept of Medical Imaging
mesh term: Atherosclerosis