xml: <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/NCT06020651</url>
    </required_header>
    <id_info>
      <org_study_id>CARDIO 05 2022</org_study_id>
      <nct_id>NCT06020651</nct_id>
    </id_info>
    <brief_title>Vascular Toxicities of Immune ChecKpoint Inhibitors : From Bed to Benchside</brief_title>
    <acronym>VICKI</acronym>
    <official_title>Vascular Toxicities of Immune ChecKpoint Inhibitors : From Bed to Benchside</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Institut Mutualiste Montsouris</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Institut Mutualiste Montsouris</source>
    <oversight_info>
      <has_dmc>Yes</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>
        Immune checkpoint inhibitors (ICIs) are largely prescribed in a growing number of cancer&#xD;
        diseases and at earlier stages (non metastatic cancer). Among immune-related adverse events,&#xD;
        (iRAEs), the incidence of major cardiovascular events due to atherosclerosis reaches 13% at&#xD;
        one year in patients at high risk. To the best of our knowledge, the mechanisms of this&#xD;
        acceleration of atherosclerosis have not been studied to this date.&#xD;
  &#xD;
        The VICKI study aims at furthering our knowledge on the mechanisms of atherosclerotic plaque&#xD;
        instability by means of a prospective single-centre pilot study, by comparing:&#xD;
  &#xD;
          -  surrogate markers of clinical vasculo-toxicity with arterial Doppler (flow mediated&#xD;
             reserve) as defined by the International Cardio-Oncology Society;&#xD;
  &#xD;
          -  circulating biomarkers&#xD;
  &#xD;
        Before and after receiving ICIs for solid cancer treatment.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Context. Immune checkpoint inhibitors (ICIs) are largely prescribed in a growing number of&#xD;
        cancer diseases and at earlier stages (non metastatic cancer). Among immune-related adverse&#xD;
        events, (iRAEs), the incidence of major cardiovascular events due to atherosclerosis reaches&#xD;
        13% at one year in patients at high risk. To the best of our knowledge, the mechanisms of&#xD;
        this acceleration of atherosclerosis have not been studied to this date.&#xD;
  &#xD;
        Endothelial dysfunction is a predictor of the development of atherosclerotic plaque and&#xD;
        events related to erosion or rupture. Endothelial dysfunction correlates well with the&#xD;
        increase of circulating microparticles in various populations. The increase of circulating&#xD;
        microparticles is also associated with major cardiovascular events.&#xD;
  &#xD;
        The International society of Cardio-Oncology (IC-OS) recently published a definition for&#xD;
        subclinical vascular toxicities due to ICIs. It includes non-invasive imaging methods readily&#xD;
        available at the bedside (Herrmann et al. European Heart Journal 2022), largely replicated in&#xD;
        the recent European Society of Cardiology (ESC) guidelines 2022. It includes the decrease of&#xD;
        flow mediated reserve &lt;7% or hyperhemia index &lt;2; or the decrease of any of these biomarkers&#xD;
        &gt; 50% from baseline.&#xD;
  &#xD;
        Aims and Methods. The VICKI study aims at furthering our knowledge on the mechanisms of&#xD;
        atherosclerotic plaque instability by means of a prospective single-centre pilot study, by&#xD;
        comparing:&#xD;
  &#xD;
          -  surrogate markers of clinical vasculo-toxicity with arterial Doppler (flow mediated&#xD;
             reserve, hyperhemia index, plaque volume) as defined by IC-OS;&#xD;
  &#xD;
          -  circulating microparticles; Before and after receiving ICIs for solid cancer treatment.&#xD;
  &#xD;
        The number of participants:&#xD;
  &#xD;
          -  40 patients receiving ICIs for solid cancer (alone or in combination of other cancer&#xD;
             drugs);&#xD;
  &#xD;
          -  40 controls (matched by age, gender, cancer type) not treated by ICIs.&#xD;
  &#xD;
        Duration of participation: up to 6 weeks. Inclusion period: 12 months.&#xD;
  &#xD;
        Perspectives. The VICKI study may improve our understanding of the mechanisms of&#xD;
        atherosclerosis mediated major cardiovascular events. If circulating biomarkers correlate&#xD;
        well with Doppler surrogate markers of vascular toxicity, larger studies to refine prediction&#xD;
        models could be undertaken. This would be a step forward personalized care for the prediction&#xD;
        of major cardiovascular events on ICIs.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">June 7, 2023</start_date>
    <completion_date type="Anticipated">June 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 30, 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>All participants will undergo the same cardiovascular assessment; only cancer therapies differ according to standard of care.</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Endothelial dysfunction</measure>
      <time_frame>6 weeks</time_frame>
      <description>Surrogate marker of endothelial dysfunction : Signifiant FMD variation on ICIs as defined by the International Cardio-Oncology Society</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Correlation of blood biomarkers to endothelial dysfunction (surrogate marker: Flow Mediated Dilatation variation)</measure>
      <time_frame>6 weeks</time_frame>
      <description>Increase in microparticles (CD144+, CD31+/41-, CD62e+, CD235a+, CD41+, CD11+, CD3+); cytokines (e.g., IL-1b, IFNg, TNFa, VEGF-A, C, D, HGF); single-cell profiling and deep immunophenotyping.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Major cardiovascular event (MACE)</measure>
      <time_frame>6 months</time_frame>
      <description>Collection of clinically relevant MACE at clinical follow-up: acute coronary syndrome; coronary angioplasty; stroke; cardiac suddent death, myocarditis, myositis.</description>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Renal Cell Carcinoma</condition>
    <condition>Bladder Cancer</condition>
    <condition>MSI-H Cancer</condition>
    <condition>Cancer</condition>
    <arm_group>
      <arm_group_label>ICIs alone</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants on ICIs alone</description>
    </arm_group>
    <arm_group>
      <arm_group_label>ICIs + VEGF inhibitors</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants on ICIs + VEGF inhibitors</description>
    </arm_group>
    <arm_group>
      <arm_group_label>ICIs + chemotherapy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants on ICIs + chemotherapy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Controls</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
      <description>Participants on other than ICIs cancer therapies</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Arterial Doppler for Flow Mediated Reserve measurement</intervention_name>
      <description>Arterial Doppler (ultrasound, no radiation, no contrast agent) and blood sampling twice for participants on ICIs</description>
      <arm_group_label>Controls</arm_group_label>
      <arm_group_label>ICIs + VEGF inhibitors</arm_group_label>
      <arm_group_label>ICIs + chemotherapy</arm_group_label>
      <arm_group_label>ICIs alone</arm_group_label>
      <other_name>Blood sampling</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  All patients scheduled for first ICI therapy at our institution;&#xD;
  &#xD;
            -  Matched controls with cancer and no ICI therapy;&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Major cardiovascular event in the past 6 months;&#xD;
  &#xD;
            -  Unable to provide informed consent;&#xD;
  &#xD;
            -  History of ICI therapy&#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>Isabelle Sauret, MBS</last_name>
      <phone>+33 1 56 61</phone>
      <phone_ext>6705</phone_ext>
      <email>isabelle.sauret@imm.fr</email>
    </overall_contact>
    <location>
      <facility>
        <name>INstitut Mutualiste Montsouris</name>
        <address>
          <city>Paris</city>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Mariana Mirabel, MD, PhD</last_name>
        <phone>+33 1 56 61</phone>
        <phone_ext>6479</phone_ext>
        <email>mariana.mirabel@imm.fr</email>
      </contact>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 27, 2023</study_first_submitted>
    <study_first_submitted_qc>August 29, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 31, 2023</study_first_posted>
    <last_update_submitted>August 29, 2023</last_update_submitted>
    <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 31, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Atherosclerosis</keyword>
    <keyword>Cancer</keyword>
    <keyword>Immune Checkpoint Inhibitor</keyword>
    <keyword>Vascular Diseases</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma, Renal Cell</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06020651
  org study id: CARDIO 05 2022
  nct id: NCT06020651
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Immune checkpoint inhibitors (ICIs) are largely prescribed in a growing number of cancer
        diseases and at earlier stages (non metastatic cancer). Among immune-related adverse events,
        (iRAEs), the incidence of major cardiovascular events due to atherosclerosis reaches 13% at
        one year in patients at high risk. To the best of our knowledge, the mechanisms of this
        acceleration of atherosclerosis have not been studied to this date.
  
        The VICKI study aims at furthering our knowledge on the mechanisms of atherosclerotic plaque
        instability by means of a prospective single-centre pilot study, by comparing:
  
          -  surrogate markers of clinical vasculo-toxicity with arterial Doppler (flow mediated
             reserve) as defined by the International Cardio-Oncology Society;
  
          -  circulating biomarkers
  
        Before and after receiving ICIs for solid cancer treatment.
  Context. Immune checkpoint inhibitors (ICIs) are largely prescribed in a growing number of
        cancer diseases and at earlier stages (non metastatic cancer). Among immune-related adverse
        events, (iRAEs), the incidence of major cardiovascular events due to atherosclerosis reaches
        13% at one year in patients at high risk. To the best of our knowledge, the mechanisms of
        this acceleration of atherosclerosis have not been studied to this date.
  
        Endothelial dysfunction is a predictor of the development of atherosclerotic plaque and
        events related to erosion or rupture. Endothelial dysfunction correlates well with the
        increase of circulating microparticles in various populations. The increase of circulating
        microparticles is also associated with major cardiovascular events.
  
        The International society of Cardio-Oncology (IC-OS) recently published a definition for
        subclinical vascular toxicities due to ICIs. It includes non-invasive imaging methods readily
        available at the bedside (Herrmann et al. European Heart Journal 2022), largely replicated in
        the recent European Society of Cardiology (ESC) guidelines 2022. It includes the decrease of
        flow mediated reserve <7% or hyperhemia index <2; or the decrease of any of these biomarkers
        > 50% from baseline.
  
        Aims and Methods. The VICKI study aims at furthering our knowledge on the mechanisms of
        atherosclerotic plaque instability by means of a prospective single-centre pilot study, by
        comparing:
  
          -  surrogate markers of clinical vasculo-toxicity with arterial Doppler (flow mediated
             reserve, hyperhemia index, plaque volume) as defined by IC-OS;
  
          -  circulating microparticles; Before and after receiving ICIs for solid cancer treatment.
  
        The number of participants:
  
          -  40 patients receiving ICIs for solid cancer (alone or in combination of other cancer
             drugs);
  
          -  40 controls (matched by age, gender, cancer type) not treated by ICIs.
  
        Duration of participation: up to 6 weeks. Inclusion period: 12 months.
  
        Perspectives. The VICKI study may improve our understanding of the mechanisms of
        atherosclerosis mediated major cardiovascular events. If circulating biomarkers correlate
        well with Doppler surrogate markers of vascular toxicity, larger studies to refine prediction
        models could be undertaken. This would be a step forward personalized care for the prediction
        of major cardiovascular events on ICIs.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  intervention model description: All participants will undergo the same cardiovascular assessment; only cancer therapies differ according to standard of care.
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: Endothelial dysfunction
  time frame: 6 weeks
  description: Surrogate marker of endothelial dysfunction : Signifiant FMD variation on ICIs as defined by the International Cardio-Oncology Society
  measure: Correlation of blood biomarkers to endothelial dysfunction (surrogate marker: Flow Mediated Dilatation variation)
  time frame: 6 weeks
  description: Increase in microparticles (CD144+, CD31+/41-, CD62e+, CD235a+, CD41+, CD11+, CD3+); cytokines (e.g., IL-1b, IFNg, TNFa, VEGF-A, C, D, HGF); single-cell profiling and deep immunophenotyping.
  measure: Major cardiovascular event (MACE)
  time frame: 6 months
  description: Collection of clinically relevant MACE at clinical follow-up: acute coronary syndrome; coronary angioplasty; stroke; cardiac suddent death, myocarditis, myositis.
  arm group label: ICIs alone
  arm group type: Experimental
  description: Participants on ICIs alone
  arm group label: ICIs + VEGF inhibitors
  arm group type: Experimental
  description: Participants on ICIs + VEGF inhibitors
  arm group label: ICIs + chemotherapy
  arm group type: Experimental
  description: Participants on ICIs + chemotherapy
  arm group label: Controls
  arm group type: Sham Comparator
  description: Participants on other than ICIs cancer therapies
  intervention type: Diagnostic Test
  intervention name: Arterial Doppler for Flow Mediated Reserve measurement
  description: Arterial Doppler (ultrasound, no radiation, no contrast agent) and blood sampling twice for participants on ICIs
  arm group label: Controls
  arm group label: ICIs + VEGF inhibitors
  arm group label: ICIs + chemotherapy
  arm group label: ICIs alone
  other name: Blood sampling
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Isabelle Sauret, MBS
  phone: +33 1 56 61
  phone ext: 6705
  email: isabelle.sauret@imm.fr
  facility: 
  status: Recruiting
  contact: 
  country: France
  responsible party type: Sponsor
  mesh term: Carcinoma, Renal Cell
  sharing ipd: No