<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/NCT03031873</url>
  </required_header>
  <id_info>
    <org_study_id>3T MRI evaluation</org_study_id>
    <nct_id>NCT03031873</nct_id>
  </id_info>
  <brief_title>Evaluation of Susceptibility-weighted Magnetic Resonance Imaging and 4d-time-resolved Magnetic Resonance Angiography in Brain Arteriovenous Malformations</brief_title>
  <official_title>Evaluation of Susceptibility-weighted Magnetic Resonance Imaging and 4d-time-resolved Magnetic Resonance Angiography in Brain Arteriovenous Malformations</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ottawa Hospital Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ottawa Hospital Research Institute</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>
      Brain arteriovenous malformations are abnormal communications between brain arteries and&#xD;
      veins with an intervening tangle of abnormal arteries (nidus). Brain AVMs may be asymptomatic&#xD;
      or symptomatic, presenting with acute hemorrhage or neurological symptoms. Brain AVMs that&#xD;
      have not bled carry a yearly risk of intracranial hemorrhage of approximately 4% (Ondra et&#xD;
      al.).&#xD;
&#xD;
      The management is multidisciplinary involving neurosurgeons, interventional&#xD;
      neuroradiologists, radiation physicians, neurologists and allied health care personnel.&#xD;
      Patients may be treated with open neurosurgery, endovascular embolization, radiation therapy&#xD;
      or any combination of these treatments. The goal of the treatment is to eliminate the brain&#xD;
      AVM while preserving normal flow to the surrounding normal arteries. This involves&#xD;
      obliteration of the shunting of blood via the AVM arteries to veins by a variety of&#xD;
      treatments. The treatment regimen is individualized dependent on natural history, the&#xD;
      angioarchitecture, location, risk of treatment(s) and patient wishes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Why is MRI important in the management of brain AVMs i.e. over conventional catheter&#xD;
      angiography? The &quot;gold standard&quot; for evaluation of brain AVMs is catheter angiography.&#xD;
      However, the procedure is invasive, involves ionizing radiation, exposure to contrast media&#xD;
      with potential for nephrotoxicity or allergy and carries a 1% risk of morbidity including&#xD;
      stroke. In contrast, MRI is a non-invasive method to evaluate brain AVMs and has the added&#xD;
      advantage over catheter angiography of depicting the anatomical localization of the AVM&#xD;
      within the brain tissue. However, currently MRI is limited by lack of ability to demonstrate&#xD;
      shunting of blood through the AVM, an important indicator that the brain AVM is still present&#xD;
      after treatment.&#xD;
&#xD;
      Susceptibility-weighted imaging (SWI) is a promising new MRI technology which indirectly&#xD;
      evaluates the amount of oxygen within blood vessels. Small case series exploring the utility&#xD;
      of SWI in brain AVMs has been reported suggesting the venous drainage of brain AVMs is often&#xD;
      abnormally hyperintense because of abnormal shunting of oxygenated blood from AVM arteries to&#xD;
      the draining vein(Bharathi D et al.). Typically in normal tissues, oxygenated blood on SWI&#xD;
      images is hyperintense while deoxygenated blood in normal veins is hypointense. Developmental&#xD;
      venous anomalies demonstrating enlarged draining veins are normal variants that must be&#xD;
      distinguished from true AVMs . However, this capability has not been prospectively evaluated&#xD;
      in a systematic fashion.&#xD;
&#xD;
      Our current standard for contrast-enhanced evaluation of brain AVMs is to perform a&#xD;
      contrast-enhanced MRA (CEMRA) followed by a post-contrast T1 volumetric whole brain sequence.&#xD;
      The CEMRA allows depiction of contrast at its maximal intensity passing through the brain on&#xD;
      its first pass. The post contrast T1 scan only demonstrates static contrast pooling within&#xD;
      the brain AVM. However, neither CEMRA nor the post contrast scan provides information about&#xD;
      the speed at which contrast is moving through a brain AVM ie. shunting. Evaluation of the&#xD;
      temporal passage of contrast brain AVM would require a dynamic time-resolved technique with&#xD;
      adequate temporal resolution to distinguish early vs late vs no shunting within a brain AVM.&#xD;
&#xD;
      What is the current technology for MRI of brain AVMs? Susceptibility-weighted angiography&#xD;
      (SWAN) imaging on the GE 3 T has been attempted but the preliminary evidence suggest that the&#xD;
      images are of low resolution and difficult to interpret. In addition, our literature review&#xD;
      found a paucity of studies evaluating staged treatment of brain AVMs with SWAN imaging. In&#xD;
      our institution, brain AVMs may have staged treatment consistent of endovascular embolization&#xD;
      and/or radiosurgery. After each treatment patients are followed with serial imaging MRI and&#xD;
      Digital Subtraction Angiography (DSA). This provides an important opportunity to investigate&#xD;
      the utility of non-invasive MRI to detect residual AVM after treatment.&#xD;
&#xD;
      Thus, there is a significant opportunity to evaluate the value of SWAN and Time Resolved&#xD;
      Magnetic Resonance Angiography (TRMRA) assessment of progressive obliteration of the AVM&#xD;
      nidus. Specifically, this is attractive for brain AVMs that are treated with radiosurgery as&#xD;
      MRI and DSA are required for clinical grounds for treatment planning purposes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 1, 2020</start_date>
  <completion_date type="Anticipated">March 2024</completion_date>
  <primary_completion_date type="Anticipated">March 2024</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>SWAN and TRMRA with catheter angiography will be measured to determine if accuracy of brain MRI for follow-up of treated brain AVM can be improved</measure>
    <time_frame>24 months</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Arteriovenous Malformations</condition>
  <arm_group>
    <arm_group_label>MRI perfusion imaging</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>SWAN imaging on the GE 3 T has been attempted but the preliminary evidence suggest that the images are of low resolution and difficult to interpret. Similarly, early experience with TRMRA suggest poor spatial and temporal resolution using the standard &quot;out-of-the-box&quot; protocols.&#xD;
Thus, there is a significant opportunity to improve SWAN and TRMRA, to evaluate the evolution of progressive obliteration of the AVM nidus. Specifically, this is attractive for brain AVMs that are treated with radiosurgery as MRI is required for clinical grounds for treatment planning purposes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MRI perfusion imaging</intervention_name>
    <description>Evaluate the evolution of progressive obliteration of the AVM nidus</description>
    <arm_group_label>MRI perfusion imaging</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Informed consent&#xD;
&#xD;
          2. Brain AVMs previously diagnosed with either CT Angiography, MRI or catheter&#xD;
             angiography.&#xD;
&#xD;
          3. Undergoing cerebral catheter angiography for clinical evaluation of the brain AVM.&#xD;
             Patients with brain AVMs scheduled for catheter cerebral angiography will undergo MRI&#xD;
             (GE 3T) within 3 months.&#xD;
&#xD;
          4. Age &gt; 18 years.&#xD;
&#xD;
          5. mRS &lt;=2&#xD;
&#xD;
          6. Brain AVM visible on MRI, i.e. nidus &gt; 1 cm&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Contraindication to MRI eg. Non-MRI compatible implant, severe claustrophobia&#xD;
&#xD;
          2. Contraindication for contrast: GFR &lt; 60 ml/min, allergy to contrast&#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>Howard Lesiuk, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ottawa Hospital Research Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Howard Lesiuk, MD</last_name>
    <phone>613-798-5555</phone>
    <phone_ext>17522</phone_ext>
    <email>hlesiuk@toh.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Betty Anne Schwarz, PhD</last_name>
    <phone>613-798-5555</phone>
    <phone_ext>17520</phone_ext>
    <email>nimikhael@ohri.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The Ottawa Hospital</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1Y 4E9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Betty Anne Schwarz, PhD</last_name>
      <phone>6137985555</phone>
      <phone_ext>17522</phone_ext>
      <email>baschwarz@toh.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>June 23, 2022</last_update_submitted>
  <last_update_submitted_qc>June 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 27, 2022</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>Hemangioma</mesh_term>
    <mesh_term>Arteriovenous Malformations</mesh_term>
    <mesh_term>Congenital Abnormalities</mesh_term>
  </condition_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/NCT03031873
org study id: 3T MRI evaluation
nct id: NCT03031873
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Brain arteriovenous malformations are abnormal communications between brain arteries and
      veins with an intervening tangle of abnormal arteries (nidus). Brain AVMs may be asymptomatic
      or symptomatic, presenting with acute hemorrhage or neurological symptoms. Brain AVMs that
      have not bled carry a yearly risk of intracranial hemorrhage of approximately 4% (Ondra et
      al.).

      The management is multidisciplinary involving neurosurgeons, interventional
      neuroradiologists, radiation physicians, neurologists and allied health care personnel.
      Patients may be treated with open neurosurgery, endovascular embolization, radiation therapy
      or any combination of these treatments. The goal of the treatment is to eliminate the brain
      AVM while preserving normal flow to the surrounding normal arteries. This involves
      obliteration of the shunting of blood via the AVM arteries to veins by a variety of
      treatments. The treatment regimen is individualized dependent on natural history, the
      angioarchitecture, location, risk of treatment(s) and patient wishes.
Why is MRI important in the management of brain AVMs i.e. over conventional catheter
      angiography? The "gold standard" for evaluation of brain AVMs is catheter angiography.
      However, the procedure is invasive, involves ionizing radiation, exposure to contrast media
      with potential for nephrotoxicity or allergy and carries a 1% risk of morbidity including
      stroke. In contrast, MRI is a non-invasive method to evaluate brain AVMs and has the added
      advantage over catheter angiography of depicting the anatomical localization of the AVM
      within the brain tissue. However, currently MRI is limited by lack of ability to demonstrate
      shunting of blood through the AVM, an important indicator that the brain AVM is still present
      after treatment.

      Susceptibility-weighted imaging (SWI) is a promising new MRI technology which indirectly
      evaluates the amount of oxygen within blood vessels. Small case series exploring the utility
      of SWI in brain AVMs has been reported suggesting the venous drainage of brain AVMs is often
      abnormally hyperintense because of abnormal shunting of oxygenated blood from AVM arteries to
      the draining vein(Bharathi D et al.). Typically in normal tissues, oxygenated blood on SWI
      images is hyperintense while deoxygenated blood in normal veins is hypointense. Developmental
      venous anomalies demonstrating enlarged draining veins are normal variants that must be
      distinguished from true AVMs . However, this capability has not been prospectively evaluated
      in a systematic fashion.

      Our current standard for contrast-enhanced evaluation of brain AVMs is to perform a
      contrast-enhanced MRA (CEMRA) followed by a post-contrast T1 volumetric whole brain sequence.
      The CEMRA allows depiction of contrast at its maximal intensity passing through the brain on
      its first pass. The post contrast T1 scan only demonstrates static contrast pooling within
      the brain AVM. However, neither CEMRA nor the post contrast scan provides information about
      the speed at which contrast is moving through a brain AVM ie. shunting. Evaluation of the
      temporal passage of contrast brain AVM would require a dynamic time-resolved technique with
      adequate temporal resolution to distinguish early vs late vs no shunting within a brain AVM.

      What is the current technology for MRI of brain AVMs? Susceptibility-weighted angiography
      (SWAN) imaging on the GE 3 T has been attempted but the preliminary evidence suggest that the
      images are of low resolution and difficult to interpret. In addition, our literature review
      found a paucity of studies evaluating staged treatment of brain AVMs with SWAN imaging. In
      our institution, brain AVMs may have staged treatment consistent of endovascular embolization
      and/or radiosurgery. After each treatment patients are followed with serial imaging MRI and
      Digital Subtraction Angiography (DSA). This provides an important opportunity to investigate
      the utility of non-invasive MRI to detect residual AVM after treatment.

      Thus, there is a significant opportunity to evaluate the value of SWAN and Time Resolved
      Magnetic Resonance Angiography (TRMRA) assessment of progressive obliteration of the AVM
      nidus. Specifically, this is attractive for brain AVMs that are treated with radiosurgery as
      MRI and DSA are required for clinical grounds for treatment planning purposes.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: SWAN and TRMRA with catheter angiography will be measured to determine if accuracy of brain MRI for follow-up of treated brain AVM can be improved
time frame: 24 months
arm group label: MRI perfusion imaging
arm group type: Other
description: SWAN imaging on the GE 3 T has been attempted but the preliminary evidence suggest that the images are of low resolution and difficult to interpret. Similarly, early experience with TRMRA suggest poor spatial and temporal resolution using the standard "out-of-the-box" protocols.
Thus, there is a significant opportunity to improve SWAN and TRMRA, to evaluate the evolution of progressive obliteration of the AVM nidus. Specifically, this is attractive for brain AVMs that are treated with radiosurgery as MRI is required for clinical grounds for treatment planning purposes.
intervention type: Device
intervention name: MRI perfusion imaging
description: Evaluate the evolution of progressive obliteration of the AVM nidus
arm group label: MRI perfusion imaging
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Howard Lesiuk, MD
role: Principal Investigator
affiliation: Ottawa Hospital Research Institute
last name: Howard Lesiuk, MD
phone: 613-798-5555
phone ext: 17522
email: hlesiuk@toh.ca
last name: Betty Anne Schwarz, PhD
phone: 613-798-5555
phone ext: 17520
email: nimikhael@ohri.ca
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Sponsor
mesh term: Hemangioma
mesh term: Arteriovenous Malformations
mesh term: Congenital Abnormalities
sharing ipd: Undecided