<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/NCT03291093</url>
  </required_header>
  <id_info>
    <org_study_id>NL58543.068.16</org_study_id>
    <nct_id>NCT03291093</nct_id>
  </id_info>
  <brief_title>18F-Flutemetamol and Plaque Vulnerability</brief_title>
  <official_title>Identification of Plaque Vulnerability Wit PET/MRI: a Feasibility Study of 18F-Flutemetamol in Atherosclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maastricht University Medical Center</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rationale: Amyloid beta (Ab) is mainly known for its role in Alzheimer's disease (AD)&#xD;
      pathology. However, Ab seems not only to be involved in AD pathology, but also in&#xD;
      atherosclerosis, which might explain the remarkable similarities in risk factors between&#xD;
      these two pathologies. In vitro studies suggest that a major part of this association is&#xD;
      based on the ability of amyloid to lead to macrophage activation and thus inflammation. These&#xD;
      data lead to the hypothesis that Ab is associated with plaque vulnerability.&#xD;
&#xD;
      18F-Flutemetamol is a PET tracer with high affinity for Ab. This has been extensively studied&#xD;
      in AD patients.&#xD;
&#xD;
      Objective: To validate 18F-Flutemetamol PET in the evaluation of plaque vulnerability.&#xD;
&#xD;
      Study design: A cross-sectional validation study. Study population: 25 adults, who have&#xD;
      recently (&lt;14days) experienced a transient ischemic attack (TIA) or stroke with a carotid&#xD;
      artery plaque of ≥30% and without evidence of another etiology than carotid atherosclerosis&#xD;
      (i.e. cardiac or small vessel).&#xD;
&#xD;
      Of these 25 patients, 10 patients will be included who have been scheduled for carotid&#xD;
      endarterectomy (CEA). The other 15 will be selected of patients who are not scheduled to&#xD;
      undergo CEA.&#xD;
&#xD;
      Intervention: All patients will undergo a PET/MRI scan with 18F-Flutemetamol, either before&#xD;
      the scheduled CEA or within the first 30 days following the cerebrovascular event. Imaging&#xD;
      will include the carotid and coronary arteries as well as the brain.&#xD;
&#xD;
      Main study parameters/endpoints: Tracer uptake in the carotid artery will be correlated to&#xD;
      vulnerable plaque characteristics as assessed by MRI. In the 10 CEA patients, tracer uptake&#xD;
      and MR imaging of different plaque characteristics will be validated with plaque histology of&#xD;
      the surgically removed specimen.&#xD;
&#xD;
      Nature and extent of the burden and risks associated with participation, benefit and group&#xD;
      relatedness: There is no additional benefit for study subjects. Study subjects will receive&#xD;
      the same treatment as non-participating patients. Patients will be screened for in- and&#xD;
      exclusion criteria to minimize risks.&#xD;
&#xD;
      For optimal MR imaging patients will be injected with a Gadolinium based contrast agent,&#xD;
      which is a common procedure and associated with very low risk of complications. The PET&#xD;
      tracer 18F-flutemetamol has been studied extensively and is currently used in patients with&#xD;
      AD. Adverse events were not frequent and mainly mild. The radioactivity dose will be around&#xD;
      6.8 mSv.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 1, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2019</primary_completion_date>
  <phase>Phase 2/Phase 3</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>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>18F-Flutemetamol uptake carotids</measure>
    <time_frame>0-120min</time_frame>
    <description>measured as SUV and TBR</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>18F-Flutemetamol uptake coronaries</measure>
    <time_frame>0-150min</time_frame>
    <description>measured as SUV and TBR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>18F-Flutemetamol uptake in the brain</measure>
    <time_frame>0-150min</time_frame>
    <description>measured as SUVR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CEA - plaque inflammation</measure>
    <time_frame>1-14 dys</time_frame>
    <description>macrophage content</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRI plaque characteristics carotid</measure>
    <time_frame>0-150min</time_frame>
    <description>semi quantitive analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CEA - plaque amyloid burden</measure>
    <time_frame>1-14 dys</time_frame>
    <description>Immunohistochemistry</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">25</enrollment>
  <condition>Atherosclerosis</condition>
  <arm_group>
    <arm_group_label>18F-Flutemetamol PET/MRI dynamic</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All included patients will be patients with a recent stroke and a significant carotid plaque.&#xD;
The first 5 patients will undergo a slightly longer scan protocol to determine optimal scan time for the use of 18F-Flutemetamol in atherosclerosis imaging.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>18F-Flutemetamol PET/MRI CEA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 patients will be selected from patients that will undergo carotid endarterectomy (CEA) and will undergo the the optimized (shorter) scan protocol with 18F-Flutemetamol. The decision for this operation is made by the surgeon and neurologist and based on clinical standards and is thus independent of study participation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>18F-Flutemetamol PET/MRI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The remaining 10 patients will undergo the optimized (shorter) scan protocol with 18F-Flutemetamol.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>18F-Flutemetamol PET/MRI</intervention_name>
    <description>All patients will undergo a PET/MRI of the carotids after 18F-Flutemetamol injection.</description>
    <arm_group_label>18F-Flutemetamol PET/MRI</arm_group_label>
    <arm_group_label>18F-Flutemetamol PET/MRI CEA</arm_group_label>
    <arm_group_label>18F-Flutemetamol PET/MRI dynamic</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        In order to be eligible to participate in this study, a subject must meet all of the&#xD;
        following criteria:&#xD;
&#xD;
          -  All patients:&#xD;
&#xD;
               -  Age18years and older (no maximum age)&#xD;
&#xD;
               -  Informed consent by signed informed consent form regarding this study&#xD;
&#xD;
          -  Patients, who are scheduled for carotid endarterectomy:&#xD;
&#xD;
             o Inclusion criteria for carotid endarterectomy:&#xD;
&#xD;
               -  Symptomatic stenosis (TIA or CVA) within last 14days and high grade stenosis&#xD;
                  (70-99%)&#xD;
&#xD;
               -  In men, carotid artery stenosis between 50-69% is considered significant when&#xD;
                  related to clinical symptoms&#xD;
&#xD;
          -  Patients, who are not scheduled for carotid endarterectomy:&#xD;
&#xD;
               -  Patients who have experienced a TIA/CVA/amaurosis fugax (a 'TIA of the eye')&#xD;
                  within the last 14 days and abnormal findings on imaging of the carotids:&#xD;
&#xD;
                    -  Women with an ipsilateral carotid artery stenosis between 30-69% based on&#xD;
                       duplex ultrasonography, CTA, or MRA&#xD;
&#xD;
                    -  Men with an ipsilateral carotid artery stenosis between 30-49% based on&#xD;
                       duplex ultrasonography, CTA, or MRA&#xD;
&#xD;
                    -  Patients meeting inclusion criteria for carotid endarterectomy, but with&#xD;
                       contra- indications for CEA&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  All patients:&#xD;
&#xD;
               -  Severe cognitive impairment, neurological deficit or comorbidity causing the&#xD;
                  study to be too high a burden for the patient or disrupting patient's co-&#xD;
                  operation with scan procedures&#xD;
&#xD;
               -  Evident other causality for stroke (cardiac embolus, small vessel disease or&#xD;
                  thrombogenic diathesis)&#xD;
&#xD;
               -  Pregnant women and nursing mothers&#xD;
&#xD;
               -  Contra-indications for MRI (49):&#xD;
&#xD;
                    -  Ferromagnetic implants, such as pacemakers and other electronic implants&#xD;
&#xD;
                    -  Ferromagnetic (intracerebral) vascular clips&#xD;
&#xD;
                    -  Metallic cochlear implants&#xD;
&#xD;
                    -  Metallic splinters in eye(s) or other magnetic metallic foreign bodies&#xD;
                       elsewhere&#xD;
&#xD;
                    -  Claustrophobia&#xD;
&#xD;
               -  Relative contra-indications for MRI-contrast agents (50):&#xD;
&#xD;
                    -  GFR &lt;30ml/min/1,73m2&#xD;
&#xD;
                    -  Previous allergic reaction to MRI contrast agent&#xD;
&#xD;
               -  Contra-indication 18F-Flutemetamol:&#xD;
&#xD;
                    -  Known allergic reaction to flutemetamol or polysorbate 80 or any of the&#xD;
                       excipients.&#xD;
&#xD;
                    -  Severe liver dysfunction.&#xD;
&#xD;
          -  Patients undergoing CEA:&#xD;
&#xD;
               -  Comorbidity associated with high operative risk&#xD;
&#xD;
               -  Occlusion of the internal carotid artery on the symptomatic side&#xD;
&#xD;
               -  Near occlusion on the symptomatic side&#xD;
&#xD;
               -  Complete infarction of the symptomatic anterior circulation/severe neurological&#xD;
                  deficit&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Maastricht University Medical Centre (MUMC+)</name>
      <address>
        <city>Maastricht</city>
        <state>Limburg</state>
        <zip>6229 HX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ellen Boswijk, MD</last_name>
      <phone>+31433876549</phone>
      <email>ellen.boswijk@mumc.nl</email>
    </contact>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>September 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>July 10, 2019</last_update_submitted>
  <last_update_submitted_qc>July 10, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PET/MRI</keyword>
  <keyword>Amyloid</keyword>
  <keyword>Flutemetamol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atherosclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Flutemetamol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03291093
org study id: NL58543.068.16
nct id: NCT03291093
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
Rationale: Amyloid beta (Ab) is mainly known for its role in Alzheimer's disease (AD)
      pathology. However, Ab seems not only to be involved in AD pathology, but also in
      atherosclerosis, which might explain the remarkable similarities in risk factors between
      these two pathologies. In vitro studies suggest that a major part of this association is
      based on the ability of amyloid to lead to macrophage activation and thus inflammation. These
      data lead to the hypothesis that Ab is associated with plaque vulnerability.

      18F-Flutemetamol is a PET tracer with high affinity for Ab. This has been extensively studied
      in AD patients.

      Objective: To validate 18F-Flutemetamol PET in the evaluation of plaque vulnerability.

      Study design: A cross-sectional validation study. Study population: 25 adults, who have
      recently (<14days) experienced a transient ischemic attack (TIA) or stroke with a carotid
      artery plaque of ≥30% and without evidence of another etiology than carotid atherosclerosis
      (i.e. cardiac or small vessel).

      Of these 25 patients, 10 patients will be included who have been scheduled for carotid
      endarterectomy (CEA). The other 15 will be selected of patients who are not scheduled to
      undergo CEA.

      Intervention: All patients will undergo a PET/MRI scan with 18F-Flutemetamol, either before
      the scheduled CEA or within the first 30 days following the cerebrovascular event. Imaging
      will include the carotid and coronary arteries as well as the brain.

      Main study parameters/endpoints: Tracer uptake in the carotid artery will be correlated to
      vulnerable plaque characteristics as assessed by MRI. In the 10 CEA patients, tracer uptake
      and MR imaging of different plaque characteristics will be validated with plaque histology of
      the surgically removed specimen.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness: There is no additional benefit for study subjects. Study subjects will receive
      the same treatment as non-participating patients. Patients will be screened for in- and
      exclusion criteria to minimize risks.

      For optimal MR imaging patients will be injected with a Gadolinium based contrast agent,
      which is a common procedure and associated with very low risk of complications. The PET
      tracer 18F-flutemetamol has been studied extensively and is currently used in patients with
      AD. Adverse events were not frequent and mainly mild. The radioactivity dose will be around
      6.8 mSv.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Single (Outcomes Assessor)
measure: 18F-Flutemetamol uptake carotids
time frame: 0-120min
description: measured as SUV and TBR
measure: 18F-Flutemetamol uptake coronaries
time frame: 0-150min
description: measured as SUV and TBR
measure: 18F-Flutemetamol uptake in the brain
time frame: 0-150min
description: measured as SUVR
measure: CEA - plaque inflammation
time frame: 1-14 dys
description: macrophage content
measure: MRI plaque characteristics carotid
time frame: 0-150min
description: semi quantitive analysis
measure: CEA - plaque amyloid burden
time frame: 1-14 dys
description: Immunohistochemistry
arm group label: 18F-Flutemetamol PET/MRI dynamic
arm group type: Experimental
description: All included patients will be patients with a recent stroke and a significant carotid plaque.
The first 5 patients will undergo a slightly longer scan protocol to determine optimal scan time for the use of 18F-Flutemetamol in atherosclerosis imaging.
arm group label: 18F-Flutemetamol PET/MRI CEA
arm group type: Experimental
description: 10 patients will be selected from patients that will undergo carotid endarterectomy (CEA) and will undergo the the optimized (shorter) scan protocol with 18F-Flutemetamol. The decision for this operation is made by the surgeon and neurologist and based on clinical standards and is thus independent of study participation.
arm group label: 18F-Flutemetamol PET/MRI
arm group type: Experimental
description: The remaining 10 patients will undergo the optimized (shorter) scan protocol with 18F-Flutemetamol.
intervention type: Drug
intervention name: 18F-Flutemetamol PET/MRI
description: All patients will undergo a PET/MRI of the carotids after 18F-Flutemetamol injection.
arm group label: 18F-Flutemetamol PET/MRI
arm group label: 18F-Flutemetamol PET/MRI CEA
arm group label: 18F-Flutemetamol PET/MRI dynamic
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
status: Recruiting
contact: 
country: Netherlands
responsible party type: Sponsor
mesh term: Atherosclerosis
mesh term: Flutemetamol
sharing ipd: Undecided