<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/NCT03234257</url>
  </required_header>
  <id_info>
    <org_study_id>2016-03</org_study_id>
    <nct_id>NCT03234257</nct_id>
  </id_info>
  <brief_title>Evaluation of the Carotid Plaque Stability by Ultrafast-ultrasound Imaging (UF)</brief_title>
  <acronym>UF-Plaques</acronym>
  <official_title>Evaluation of the Carotid Plaque Stability by Ultrafast-ultrasound Imaging (UF)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>French Cardiology Society</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>INSERM U979 (Institut Langevin)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>French Cardiology Society</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Unstable plaques are characterized by lower segmental stiffness and intimal&#xD;
      neovascularization compared to stable plaques. Our objective is to determine the capacity of&#xD;
      the elastographic parameters obtained by the UF to discriminate the unstable to the stable&#xD;
      plaques. We hope to improve the stroke prediction in asymptomatic patients with carotid&#xD;
      stenosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Context&#xD;
&#xD;
      Stroke is the second leading cause of death in the Western world and the leading cause of&#xD;
      major disability in the long term. About 15% of strokes are secondary to thrombosis or&#xD;
      embolization of an unstable atherosclerotic plaque of the carotid bifurcation. In these&#xD;
      symptomatic patients, the degree of carotid stenosis is correlated with the risk of early&#xD;
      recurrence. In patients with stenosis (NASCET)&gt; 70%, endarterectomy is an intervention aimed&#xD;
      at removing the carotid plaque to prevent stroke. In asymptomatic patients, the degree of&#xD;
      stenosis is a limited predictive factor and a better risk stratification is required to&#xD;
      assess the degree of the plaque vulnerability. The therapeutic decision towards&#xD;
      endarterectomy in addition to drug therapy is debated because of a variable benefit/ risk&#xD;
      balance. Several imaging parameters were studied: anfractuosity, heterogeneity, and&#xD;
      vascularization of the plaque for example, without allowing a modification of the current&#xD;
      recommendations. Our objective is to improve the evaluation of the risk of stroke by the fine&#xD;
      characterization of the carotid stenosis to help the medical decision. We want to evaluate a&#xD;
      new ultrasound imaging technology called Ultrafast ultrasound imaging (UF). Ultrasound has&#xD;
      the advantage of being a non-irradiating, low-cost easily accessible.&#xD;
&#xD;
      Hypotheses&#xD;
&#xD;
      Unstable plaques are characterized by lower segmental stiffness and intimal&#xD;
      neovascularization compared to stable plaques. Our objective is to determine the capacity of&#xD;
      the elastographic parameters obtained by the UF to discriminate the unstable to the stable&#xD;
      plaques. We hope to improve the stroke prediction in asymptomatic patients with carotid&#xD;
      stenosis.&#xD;
&#xD;
      Innovative aspects&#xD;
&#xD;
      The originality of the approach is the use of an advanced imaging technique, UF, developed by&#xD;
      the Langevin Institute with Mathias Fink, and already validated in the study of arterial&#xD;
      stiffness with pulse wave analysis .&#xD;
&#xD;
      This project for the application of UF in atherosclerotic plaques stems from the ability to&#xD;
      analyze the biomechanical properties of tissues by ultrasound elastography, already developed&#xD;
      in the breast, liver and thyroid. Not only does UF determine the tissue stiffness expressed&#xD;
      in kPa (Young's modulus) of the arterial wall and therefore of the carotid plaque, but UF&#xD;
      also offers the possibility of establishing a rigidity mapping at the μm3 scale And therefore&#xD;
      to approach the variability of the rigidity inside the plaque.&#xD;
&#xD;
      Moreover, following the recent development of the Doppler UF by the Langevin Institute, the&#xD;
      capabilities of this tool in the precise detection of microvascular flows make it a&#xD;
      cutting-edge tool adapted to the study of the vascularization of the carotid plaque As well&#xD;
      as the study of the hemodynamic shear stresses that apply to the surface of the plaque.&#xD;
&#xD;
      Objective&#xD;
&#xD;
      Our objective is the development and validation of informative biomarkers of the carotid&#xD;
      plaque stability by UF in order to improve the stroke prediction in case of asymptomatic&#xD;
      stenosis. A UF-ultrasound approach is a non-irradiating, easily accessible, and low cost&#xD;
      technique.&#xD;
&#xD;
      The primary objective of this study is:&#xD;
&#xD;
      - to demonstrate a significant difference in the local stiffness measurement using UF between&#xD;
      the stable and unstable plaques, according to the histological criteria.&#xD;
&#xD;
      The secondary objectives are:&#xD;
&#xD;
        1. to compare the stiffness between plaque and its adjacent arterial segments.&#xD;
&#xD;
        2. to show a correlation between the plaque's stiffness and the histological quantification&#xD;
           of the fibrous tissue.&#xD;
&#xD;
        3. to demonstrate a correlation between the elasticity of the plaque and the histological&#xD;
           quantification of the calcifications.&#xD;
&#xD;
        4. compare the quantification of vascularization by UF Doppler with the number of&#xD;
           neovessels histologically quantified&#xD;
&#xD;
        5. To compare the quantification of the wall shear stress evaluated by UF Doppler between&#xD;
           stable and unstable plaque.&#xD;
&#xD;
        6. to compare all the different parameters used to evaluated the plaque's stability, but&#xD;
           depending on whether or not the carotid stenosis is symptomatic.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 18, 2017</start_date>
  <completion_date type="Actual">September 30, 2020</completion_date>
  <primary_completion_date type="Actual">May 5, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>local stiffness measurement</measure>
    <time_frame>the day of enrollment</time_frame>
    <description>demonstrate a significant difference in the local stiffness measurement using UF between the stable and unstable plaques, according to the histological criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>stiffness between plaque and its adjacent arterial segments</measure>
    <time_frame>The day of enrollment.</time_frame>
    <description>compare the stiffness between plaque and its adjacent arterial segmentsThe local arterial stiffness (for plaque and its adjacent segments) is evaluated by shear wave imaging (SWE) with the Aixplorer® (SuperSonic© Imaging). Dedicated SWE sequences provide a mapping of local stiffness. The value of the stiffness retained is the average of the region fixed by contouring the plate and the adjacent segments on the B-mode image.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>correlation between the plaque's stiffness and the histological quantification of the fibrous tissue.</measure>
    <time_frame>at the end of the study (5 months)</time_frame>
    <description>show a correlation between the plaque's stiffness and the histological quantification of the fibrous tissue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>correlation between the elasticity of the plaque and the histological quantification of the calcifications</measure>
    <time_frame>The quantification of the fibrous tissue is carried out in a semi-quantitative manner by a suitable scale, which will be filled in the histological analysis</time_frame>
    <description>to demonstrate a correlation between the elasticity of the plaque and the histological quantification of the calcifications.The quantification of the fibrous tissue is carried out in a semi-quantitative manner by a suitable scale, which will be filled in the histological analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the quantification of vascularization by UF Doppler with the number of neovessels histologically quantified</measure>
    <time_frame>the day of enrollment</time_frame>
    <description>compare the quantification of vascularization by UF Doppler with the number of neovessels histologically quantified. The quantification of the calcifications is carried out in a semi-quantitative manner by a suitable scale, which will be filled in the histological analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the quantification of the wall shear stress evaluated by UF Doppler between stable and unstable plaque.</measure>
    <time_frame>the day of enrollment</time_frame>
    <description>To compare the quantification of the wall shear stress evaluated by UF Doppler between stable and unstable plaque.The quantification of wall shear stress is done using the UF Doppler mode. This is the measure of the average speed of the carotid flow, in contact with the plaque.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>compare all the different parameters used to evaluated the plaque's stability, but depending on whether or not the carotid stenosis is symptomatic</measure>
    <time_frame>the day of enrollment</time_frame>
    <description>to compare all the different parameters used to evaluated the plaque's stability, but depending on whether or not the carotid stenosis is symptomatic</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">69</enrollment>
  <condition>Carotid Stenosis</condition>
  <arm_group>
    <arm_group_label>patients with carotid stenosis.</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>asymptomatic patients with carotid stenosis.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>UF-ultrasound</intervention_name>
    <description>the carotid plaque stability by UF in order to improve the stroke prediction in case of asymptomatic stenosis. A UF-ultrasound approach is a non-irradiating, easily accessible, and low cost technique</description>
    <arm_group_label>patients with carotid stenosis.</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults over 18 years, referred to H.E.G.P for carotid endarterectomy,&#xD;
&#xD;
          -  beneficiaries of a social security scheme,&#xD;
&#xD;
          -  having received research information and signed the consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-atherosclerotic carotid stenosis (post-radiation stenosis)&#xD;
&#xD;
          -  No social security coverage&#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_official>
    <last_name>Emmanuel MESSAS</last_name>
    <role>Principal Investigator</role>
    <affiliation>emmanuel.messas@aphp.fr</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hopital Europeen Georges Pompidou</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>July 10, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2017</study_first_posted>
  <last_update_submitted>August 6, 2021</last_update_submitted>
  <last_update_submitted_qc>August 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Carotid stenosis</keyword>
  <keyword>stiffness</keyword>
  <keyword>ultrafast ultrasound imaging</keyword>
  <keyword>Plaque stability</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carotid Stenosis</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/NCT03234257
org study id: 2016-03
nct id: NCT03234257
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Unstable plaques are characterized by lower segmental stiffness and intimal
      neovascularization compared to stable plaques. Our objective is to determine the capacity of
      the elastographic parameters obtained by the UF to discriminate the unstable to the stable
      plaques. We hope to improve the stroke prediction in asymptomatic patients with carotid
      stenosis.
Context

      Stroke is the second leading cause of death in the Western world and the leading cause of
      major disability in the long term. About 15% of strokes are secondary to thrombosis or
      embolization of an unstable atherosclerotic plaque of the carotid bifurcation. In these
      symptomatic patients, the degree of carotid stenosis is correlated with the risk of early
      recurrence. In patients with stenosis (NASCET)> 70%, endarterectomy is an intervention aimed
      at removing the carotid plaque to prevent stroke. In asymptomatic patients, the degree of
      stenosis is a limited predictive factor and a better risk stratification is required to
      assess the degree of the plaque vulnerability. The therapeutic decision towards
      endarterectomy in addition to drug therapy is debated because of a variable benefit/ risk
      balance. Several imaging parameters were studied: anfractuosity, heterogeneity, and
      vascularization of the plaque for example, without allowing a modification of the current
      recommendations. Our objective is to improve the evaluation of the risk of stroke by the fine
      characterization of the carotid stenosis to help the medical decision. We want to evaluate a
      new ultrasound imaging technology called Ultrafast ultrasound imaging (UF). Ultrasound has
      the advantage of being a non-irradiating, low-cost easily accessible.

      Hypotheses

      Unstable plaques are characterized by lower segmental stiffness and intimal
      neovascularization compared to stable plaques. Our objective is to determine the capacity of
      the elastographic parameters obtained by the UF to discriminate the unstable to the stable
      plaques. We hope to improve the stroke prediction in asymptomatic patients with carotid
      stenosis.

      Innovative aspects

      The originality of the approach is the use of an advanced imaging technique, UF, developed by
      the Langevin Institute with Mathias Fink, and already validated in the study of arterial
      stiffness with pulse wave analysis .

      This project for the application of UF in atherosclerotic plaques stems from the ability to
      analyze the biomechanical properties of tissues by ultrasound elastography, already developed
      in the breast, liver and thyroid. Not only does UF determine the tissue stiffness expressed
      in kPa (Young's modulus) of the arterial wall and therefore of the carotid plaque, but UF
      also offers the possibility of establishing a rigidity mapping at the μm3 scale And therefore
      to approach the variability of the rigidity inside the plaque.

      Moreover, following the recent development of the Doppler UF by the Langevin Institute, the
      capabilities of this tool in the precise detection of microvascular flows make it a
      cutting-edge tool adapted to the study of the vascularization of the carotid plaque As well
      as the study of the hemodynamic shear stresses that apply to the surface of the plaque.

      Objective

      Our objective is the development and validation of informative biomarkers of the carotid
      plaque stability by UF in order to improve the stroke prediction in case of asymptomatic
      stenosis. A UF-ultrasound approach is a non-irradiating, easily accessible, and low cost
      technique.

      The primary objective of this study is:

      - to demonstrate a significant difference in the local stiffness measurement using UF between
      the stable and unstable plaques, according to the histological criteria.

      The secondary objectives are:

        1. to compare the stiffness between plaque and its adjacent arterial segments.

        2. to show a correlation between the plaque's stiffness and the histological quantification
           of the fibrous tissue.

        3. to demonstrate a correlation between the elasticity of the plaque and the histological
           quantification of the calcifications.

        4. compare the quantification of vascularization by UF Doppler with the number of
           neovessels histologically quantified

        5. To compare the quantification of the wall shear stress evaluated by UF Doppler between
           stable and unstable plaque.

        6. to compare all the different parameters used to evaluated the plaque's stability, but
           depending on whether or not the carotid stenosis is symptomatic.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: local stiffness measurement
time frame: the day of enrollment
description: demonstrate a significant difference in the local stiffness measurement using UF between the stable and unstable plaques, according to the histological criteria.
measure: stiffness between plaque and its adjacent arterial segments
time frame: The day of enrollment.
description: compare the stiffness between plaque and its adjacent arterial segmentsThe local arterial stiffness (for plaque and its adjacent segments) is evaluated by shear wave imaging (SWE) with the Aixplorer® (SuperSonic© Imaging). Dedicated SWE sequences provide a mapping of local stiffness. The value of the stiffness retained is the average of the region fixed by contouring the plate and the adjacent segments on the B-mode image.
measure: correlation between the plaque's stiffness and the histological quantification of the fibrous tissue.
time frame: at the end of the study (5 months)
description: show a correlation between the plaque's stiffness and the histological quantification of the fibrous tissue.
measure: correlation between the elasticity of the plaque and the histological quantification of the calcifications
time frame: The quantification of the fibrous tissue is carried out in a semi-quantitative manner by a suitable scale, which will be filled in the histological analysis
description: to demonstrate a correlation between the elasticity of the plaque and the histological quantification of the calcifications.The quantification of the fibrous tissue is carried out in a semi-quantitative manner by a suitable scale, which will be filled in the histological analysis
measure: the quantification of vascularization by UF Doppler with the number of neovessels histologically quantified
time frame: the day of enrollment
description: compare the quantification of vascularization by UF Doppler with the number of neovessels histologically quantified. The quantification of the calcifications is carried out in a semi-quantitative manner by a suitable scale, which will be filled in the histological analysis
measure: the quantification of the wall shear stress evaluated by UF Doppler between stable and unstable plaque.
time frame: the day of enrollment
description: To compare the quantification of the wall shear stress evaluated by UF Doppler between stable and unstable plaque.The quantification of wall shear stress is done using the UF Doppler mode. This is the measure of the average speed of the carotid flow, in contact with the plaque.
measure: compare all the different parameters used to evaluated the plaque's stability, but depending on whether or not the carotid stenosis is symptomatic
time frame: the day of enrollment
description: to compare all the different parameters used to evaluated the plaque's stability, but depending on whether or not the carotid stenosis is symptomatic
arm group label: patients with carotid stenosis.
arm group type: Other
description: asymptomatic patients with carotid stenosis.
intervention type: Device
intervention name: UF-ultrasound
description: the carotid plaque stability by UF in order to improve the stroke prediction in case of asymptomatic stenosis. A UF-ultrasound approach is a non-irradiating, easily accessible, and low cost technique
arm group label: patients with carotid stenosis.
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Emmanuel MESSAS
role: Principal Investigator
affiliation: emmanuel.messas@aphp.fr
facility: 
country: France
responsible party type: Sponsor
mesh term: Carotid Stenosis