<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/NCT02977637</url>
  </required_header>
  <id_info>
    <org_study_id>15-001308</org_study_id>
    <nct_id>NCT02977637</nct_id>
  </id_info>
  <brief_title>MRA With Feraheme in HHT</brief_title>
  <official_title>The Use of Ferumoxytol (Feraheme) for Whole Body Magnetic Resonance Angiography in Hereditary Hemorrhagic Telangiectasia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, Los Angeles</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Magnetic resonance (MR) imaging is performed with contrast agents to highlight the blood&#xD;
      vessels and allow interpretation and diagnosis of blood vessel abnormalities. HHT (Hereditary&#xD;
      Hemorrhagic Telangiectasia) is a disease of blood vessels, and can suffer fatal bleeding if&#xD;
      abnormal blood vessels are not detected and treated early. Patients with HHT also require&#xD;
      many imaging studies through their lifetimes for surveillance of blood vessels. Many HHT&#xD;
      patients also have co-existing iron deficiency anemia from bleeding in their nose and&#xD;
      gastrointestinal tract, and receive daily iron therapy.&#xD;
&#xD;
      Ferumoxytol is an alternative MR contrast agent, which is FDA (Food and Drug Administration)&#xD;
      approved for the treatment of iron deficiency anemia. In addition, it is not associated with&#xD;
      the risks to the kidneys of the other agents. The use of ferumoxytol for MR imaging may&#xD;
      benefit the patients who do not currently receive imaging due to the contraindications of the&#xD;
      conventional contrast agents. It avoids the use of ionizing radiation. Also, the conventional&#xD;
      contrast agents are associated with risks. Iodinated contrast in CT is associated with&#xD;
      significant risks of kidney damage. Another imaging technique, MR, uses gadolinium based&#xD;
      contrast agents. Gadolinium, if used in patients with pre existing kidney dysfunction&#xD;
      (defined as GFR &lt; 30ml/min) is associated with the development of another devastating disease&#xD;
      called nephrogenic systemic fibrosis. As HHT patients will require repeated scans throughout&#xD;
      their lifetimes, this study will provide them a safer alternative.&#xD;
&#xD;
      Ten patients from the HHT clinic in whom the use of ferumoxytol as an MR agent is clinically&#xD;
      indicated will be invited to participate in this study, which will determine if MR with&#xD;
      ferumoxytol is able to detect and characterize vascular malformations in HHT.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The safety of the use of gadolinium based contrast agents in MR is a concern for the FDA,&#xD;
      with risks of development of nephrogenic systemic fibrosis and the more recent discovery of&#xD;
      accumulation of gadolinium in the brain in patients who have received multiple prior MR&#xD;
      scans.&#xD;
&#xD;
      Hereditary hemorrhagic telangiectasia (HHT) manifests with multiple vascular malformations&#xD;
      (VMs) in the skin, mucous membranes and solid organs affecting the spine, brain, liver,&#xD;
      gastrointestinal tract, pancreas, and lungs. The disease has an autosomal dominant&#xD;
      inheritance and affects 1 in 5000 individuals.&#xD;
&#xD;
      Cerebral vascular malformations occur in 23 % of HHT patients, with a bleeding risk of 0.5%&#xD;
      per year. Pulmonary AVMs occur in 15-50% of HHT patients, with a complication rate of 50%&#xD;
      ranging from fatal hemoptysis or hemothorax to stroke or cerebral abscess. Liver vascular&#xD;
      malformations are present in 32-78% of HHT patients.&#xD;
&#xD;
      The rationale for screening for vascular malformations is detection of a treatable lesion&#xD;
      prior to the development of a fatal complication. The international guidelines currently&#xD;
      recommend different first line screening tests in each organ: MRI for cerebral VMs,&#xD;
      transthoracic echocardiography for pulmonary VMs, endoscopy for gastrointestinal VMs, Doppler&#xD;
      US or CT for liver VMs.&#xD;
&#xD;
      Contrast enhanced magnetic resonance angiography (CE-MRA) may play an important role in the&#xD;
      simultaneous whole body screening of vascular malformations. The advantages of CE-MRA include&#xD;
      visualization of the entire body vasculature in one examination, high spatial resolution&#xD;
      comparable to CT, no ionizing radiation and easy of multiplanar reconstructions.&#xD;
&#xD;
      Substituting a conventional gadolinium based contrast agent (GBCA) with an ultra small, super&#xD;
      paramagnetic iron oxide agent (USPIO) e.g ferumoxytol, will eliminate any potential risk of&#xD;
      developing nephrogenic systemic fibrosis. Since 2009, ferumoxytol ('Feraheme' Advanced&#xD;
      Magnetics, Cambridge, MA) has been FDA approved for the treatment of iron deficiency anemia&#xD;
      in adult patients with chronic kidney disease. The results of prior studies suggest that&#xD;
      ferumoxytol is comparable to standard GBCAs for CE- MRA. Our experience with use of&#xD;
      ferumoxytol to date suggests that it will be a superior agent for detection of vascular&#xD;
      malformations in a range of vascular territories and that it will be uniquely capable of&#xD;
      interrogating multiple territories in one sitting, due to its highly stable intravascular&#xD;
      residence time.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">November 2018</completion_date>
  <primary_completion_date type="Actual">November 2018</primary_completion_date>
  <phase>Phase 1</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>Presence or absence of AVM</measure>
    <time_frame>Immediate</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Size of AVM</measure>
    <time_frame>Immediate</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Location of AVM</measure>
    <time_frame>Immediate</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall image quality score</measure>
    <time_frame>Immediate</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Artifact score</measure>
    <time_frame>Immediate</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vessel definition score</measure>
    <time_frame>Immediate</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of AVM feeding arteries</measure>
    <time_frame>Immediate</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dimension of largest AVM feeding artery</measure>
    <time_frame>Immediate</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of AVM draining veins</measure>
    <time_frame>Immediate</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dimension of largest AVM draining vein</measure>
    <time_frame>Immediate</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dimension of aneurysmal sac</measure>
    <time_frame>Immediate</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Hereditary Hemorrhagic Telangiectasia</condition>
  <arm_group>
    <arm_group_label>Feraheme group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients enrolled in the study will receive Feraheme MRI/MRA to detect vascular malformations. Ferumoxytol in its standard concentration (510 mg in 17 cc) will be administered IV at 0.15-0.21 mg/kg prior to MRI/MRA.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Feraheme MRI/MRA</intervention_name>
    <arm_group_label>Feraheme group</arm_group_label>
    <other_name>Ferumoxytol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Definite diagnosis of HHT (clinically or genetically confirmed)&#xD;
&#xD;
          -  Known or suspected AVMs in the brain, lung, and/or liver&#xD;
&#xD;
          -  Use of ferumoxytol as an MR agent is clinically indicated&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt;18&#xD;
&#xD;
          -  Unable to have MRI scan&#xD;
&#xD;
          -  Prior adverse reaction to ferumoxytol&#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>Justin McWilliams, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCLA</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>November 28, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 30, 2016</study_first_posted>
  <last_update_submitted>January 23, 2019</last_update_submitted>
  <last_update_submitted_qc>January 23, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, Los Angeles</investigator_affiliation>
    <investigator_full_name>Justin McWilliams, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>hht</keyword>
  <keyword>hereditary</keyword>
  <keyword>hemorrhagic</keyword>
  <keyword>telangiectasia</keyword>
  <keyword>feraheme</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Telangiectasis</mesh_term>
    <mesh_term>Telangiectasia, Hereditary Hemorrhagic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ferrosoferric Oxide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT02977637
org study id: 15-001308
nct id: NCT02977637
lead sponsor: 
has dmc: No
Magnetic resonance (MR) imaging is performed with contrast agents to highlight the blood
      vessels and allow interpretation and diagnosis of blood vessel abnormalities. HHT (Hereditary
      Hemorrhagic Telangiectasia) is a disease of blood vessels, and can suffer fatal bleeding if
      abnormal blood vessels are not detected and treated early. Patients with HHT also require
      many imaging studies through their lifetimes for surveillance of blood vessels. Many HHT
      patients also have co-existing iron deficiency anemia from bleeding in their nose and
      gastrointestinal tract, and receive daily iron therapy.

      Ferumoxytol is an alternative MR contrast agent, which is FDA (Food and Drug Administration)
      approved for the treatment of iron deficiency anemia. In addition, it is not associated with
      the risks to the kidneys of the other agents. The use of ferumoxytol for MR imaging may
      benefit the patients who do not currently receive imaging due to the contraindications of the
      conventional contrast agents. It avoids the use of ionizing radiation. Also, the conventional
      contrast agents are associated with risks. Iodinated contrast in CT is associated with
      significant risks of kidney damage. Another imaging technique, MR, uses gadolinium based
      contrast agents. Gadolinium, if used in patients with pre existing kidney dysfunction
      (defined as GFR < 30ml/min) is associated with the development of another devastating disease
      called nephrogenic systemic fibrosis. As HHT patients will require repeated scans throughout
      their lifetimes, this study will provide them a safer alternative.

      Ten patients from the HHT clinic in whom the use of ferumoxytol as an MR agent is clinically
      indicated will be invited to participate in this study, which will determine if MR with
      ferumoxytol is able to detect and characterize vascular malformations in HHT.
The safety of the use of gadolinium based contrast agents in MR is a concern for the FDA,
      with risks of development of nephrogenic systemic fibrosis and the more recent discovery of
      accumulation of gadolinium in the brain in patients who have received multiple prior MR
      scans.

      Hereditary hemorrhagic telangiectasia (HHT) manifests with multiple vascular malformations
      (VMs) in the skin, mucous membranes and solid organs affecting the spine, brain, liver,
      gastrointestinal tract, pancreas, and lungs. The disease has an autosomal dominant
      inheritance and affects 1 in 5000 individuals.

      Cerebral vascular malformations occur in 23 % of HHT patients, with a bleeding risk of 0.5%
      per year. Pulmonary AVMs occur in 15-50% of HHT patients, with a complication rate of 50%
      ranging from fatal hemoptysis or hemothorax to stroke or cerebral abscess. Liver vascular
      malformations are present in 32-78% of HHT patients.

      The rationale for screening for vascular malformations is detection of a treatable lesion
      prior to the development of a fatal complication. The international guidelines currently
      recommend different first line screening tests in each organ: MRI for cerebral VMs,
      transthoracic echocardiography for pulmonary VMs, endoscopy for gastrointestinal VMs, Doppler
      US or CT for liver VMs.

      Contrast enhanced magnetic resonance angiography (CE-MRA) may play an important role in the
      simultaneous whole body screening of vascular malformations. The advantages of CE-MRA include
      visualization of the entire body vasculature in one examination, high spatial resolution
      comparable to CT, no ionizing radiation and easy of multiplanar reconstructions.

      Substituting a conventional gadolinium based contrast agent (GBCA) with an ultra small, super
      paramagnetic iron oxide agent (USPIO) e.g ferumoxytol, will eliminate any potential risk of
      developing nephrogenic systemic fibrosis. Since 2009, ferumoxytol ('Feraheme' Advanced
      Magnetics, Cambridge, MA) has been FDA approved for the treatment of iron deficiency anemia
      in adult patients with chronic kidney disease. The results of prior studies suggest that
      ferumoxytol is comparable to standard GBCAs for CE- MRA. Our experience with use of
      ferumoxytol to date suggests that it will be a superior agent for detection of vascular
      malformations in a range of vascular territories and that it will be uniquely capable of
      interrogating multiple territories in one sitting, due to its highly stable intravascular
      residence time.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Presence or absence of AVM
time frame: Immediate
measure: Size of AVM
time frame: Immediate
measure: Location of AVM
time frame: Immediate
measure: Overall image quality score
time frame: Immediate
measure: Artifact score
time frame: Immediate
measure: Vessel definition score
time frame: Immediate
measure: Number of AVM feeding arteries
time frame: Immediate
measure: Dimension of largest AVM feeding artery
time frame: Immediate
measure: Number of AVM draining veins
time frame: Immediate
measure: Dimension of largest AVM draining vein
time frame: Immediate
measure: Dimension of aneurysmal sac
time frame: Immediate
arm group label: Feraheme group
arm group type: Experimental
description: All patients enrolled in the study will receive Feraheme MRI/MRA to detect vascular malformations. Ferumoxytol in its standard concentration (510 mg in 17 cc) will be administered IV at 0.15-0.21 mg/kg prior to MRI/MRA.
intervention type: Procedure
intervention name: Feraheme MRI/MRA
arm group label: Feraheme group
other name: Ferumoxytol
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Justin McWilliams, MD
role: Principal Investigator
affiliation: University of California, Los Angeles
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, Los Angeles
investigator full name: Justin McWilliams, MD
investigator title: Principal Investigator
mesh term: Telangiectasis
mesh term: Telangiectasia, Hereditary Hemorrhagic
mesh term: Ferrosoferric Oxide
sharing ipd: No