<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/NCT03296852</url>
  </required_header>
  <id_info>
    <org_study_id>16-001538</org_study_id>
    <nct_id>NCT03296852</nct_id>
  </id_info>
  <brief_title>Study: SONAS Ultrasound for Detecting Stroke SONAS Ultrasound for Detecting Stroke</brief_title>
  <official_title>SONAS Ultrasound Device for the Detection of Ischemic and Hemorrhagic Stroke</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Burl Concepts, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, Los Angeles</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to test a new medical device, called SONAS. The SONAS&#xD;
      device is a portable, battery-powered ultrasound device to detect strokes in the prehospital&#xD;
      environment, such as emergency vehicles (eg. ambulances, helicopters). To demonstrate the&#xD;
      safety of the device the goal is test it in a small number of healthy volunteers first.&#xD;
&#xD;
      The SONAS device will be used to detect changes in blood flow to the brain through&#xD;
      ultrasound, otherwise known as TransCranial Doppler (TCD). To date, the SONAS device has been&#xD;
      tested extensively in the laboratory, in animals and in human cadavers. The purpose of the&#xD;
      present study is to test the device for safety and efficacy in a small group of healthy&#xD;
      volunteers. This study will test the device on 10 healthy volunteers. Each volunteer will&#xD;
      have a physical examination, neurological examination, and brain MRI both before and after&#xD;
      the TCD test is performed. All of these study procedures will be performed on 1 visit,&#xD;
      lasting approximately 5 hours. The brain MRI's will be used to verify the effectiveness of&#xD;
      the SONAS device on detecting changes in blood flow to the brain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Specific Aims: Indicate the purpose of the research, specifying the problems and/or&#xD;
      hypotheses to be addressed.&#xD;
&#xD;
      Aim 1: Determine safety of the SONAS device Aim 1a: Obtain perfusion MRI (PWI) / quantitative&#xD;
      MRI Aim 1b: Obtain MRI with gadolinium (gdMRI) Aim 2: Determine feasibility to detect&#xD;
      microbubble specific frequencies&#xD;
&#xD;
      Research Design and Methods: Describe in detail the design and methodology of the study.&#xD;
&#xD;
      Since this is a 'first in human' study, testing primarily for the overall safety of the&#xD;
      diagnostic approach, the aim is to enroll only healthy volunteers (e.g. no&#xD;
      cerebro-/cardio-vascular history, no vascular risk factors etc.) into the study. We&#xD;
      anticipate a total number of N=10 volunteers to be sufficient for this study.&#xD;
&#xD;
      Step 1 After written informed consent and prior to the SONAS ultrasound study each volunteer&#xD;
      will undergo a baseline assessment in form of a physical exam, including vital signs,&#xD;
      National Institute of Health Stroke Scale (NIHSS) assessment and Modified Ranking Scale as&#xD;
      well as the assessment of the Medical History.&#xD;
&#xD;
      Step 2 Next, the volunteer will undergo a cranial MRI study. The MRI study will include a&#xD;
      perfusion-weighted sequence to assess a baseline value for brain perfusion as well as&#xD;
      gadolinium-enhanced T1-weighted images to assess the integrity of the blood-brain barrier.&#xD;
&#xD;
      Step 3&#xD;
&#xD;
      After the MRI study, the volunteer will undergo the SONAS ultrasound study. The study will be&#xD;
      performed in supine position:&#xD;
&#xD;
      Two ultrasound transducers/probes will be positioned on both sides of the volunteer's head at&#xD;
      the temporal bone (above and in front of the ear on each side). To hold the&#xD;
      transducers/probes in place a customized headset has been designed which is easy to use and&#xD;
      comforting for the proband.&#xD;
&#xD;
      Step 4 An IV line will be placed in a cubital or forearm vein. To assess a baseline value,&#xD;
      ultrasound will be transmitted following an automated protocol to increase subsequently the&#xD;
      output voltage from 5 volts to 50 volts. At each voltage step the received signals will be&#xD;
      acquired and stored. Once the maximum output voltage of 50 Volts has been reached an&#xD;
      additional 10 ultrasound pulses will be transmitted and the received data acquired. The total&#xD;
      duration of this first data acquisition is 20 seconds.&#xD;
&#xD;
      Step 5 A bolus of 1.0ml of the ultrasound contrast agent (so called 'Microbubbles') Lumason™,&#xD;
      internationally known as SonoVue (Bracco Pharmaceuticals, Italy), will be injected into the&#xD;
      IV line, followed by a 5.0ml IV bolus injection of saline. Lumason™ has been FDA approved for&#xD;
      cardiac applications to opacify the left ventricular chamber and to improve the delineation&#xD;
      of the left ventricular endocardial border. In the context of the present study Lumason™&#xD;
      would be used off-label.&#xD;
&#xD;
      Step 6 Following the IV bolus injection of Lumason™, ultrasound will be transmitted and&#xD;
      received signals acquired following the same protocol as detailed under Step 4.&#xD;
&#xD;
      Step 7 3 -5 hours after the SONAS ultrasound study has been performed Step 1 and Step 2 will&#xD;
      be repeated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 19, 2018</start_date>
  <completion_date type="Actual">January 20, 2019</completion_date>
  <primary_completion_date type="Actual">September 26, 2018</primary_completion_date>
  <phase>Early 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>Device Feasibility</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Blood brain barrier impairment by extravasation of Gadolinium into the brain tissue</measure>
    <time_frame>5 hours</time_frame>
    <description>BBB impairment will be assessed by extravasation of Gadolinium into the brain tissue. Because of its molecular weight Gadolinium cannot enter the extravascular space, unless the BBB integrity is impaired. BBB impairment causes leakage of Gadolinium in into the extravascular space which, in turn, can be visualized by T1-weighted sequences.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Stroke, Acute</condition>
  <arm_group>
    <arm_group_label>Healthy Volunteers</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>SONAS Ultrasound Device</intervention_name>
    <description>To assess a baseline value, ultrasound will be transmitted following an automated protocol to increase subsequently the output voltage from 5 volts to 50 volts. At each voltage step the received signals will be acquired and stored. Once the maximum output voltage of 50 Volts has been reached an additional 10 ultrasound pulses will be transmitted and the received data acquired. The total duration of this first data acquisition is 20 seconds. Following the IV bolus injection of Lumason™, ultrasound will be transmitted and received signals acquired following the same protocol as before.</description>
    <arm_group_label>Healthy Volunteers</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lumason</intervention_name>
    <description>An IV line will be placed in a cubital or forearm vein. A bolus of 1.0ml of the ultrasound contrast agent (so called 'Microbubbles') Lumason™, internationally known as SonoVue (Bracco Pharmaceuticals, Italy), will be injected into the IV line, followed by a 5.0ml IV bolus injection of saline. Lumason™ has been FDA approved for cardiac applications to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border. In the context of the present study Lumason™ would be used off-label.</description>
    <arm_group_label>Healthy Volunteers</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be at least 18 years of age&#xD;
&#xD;
          -  No prior history of cerebro- or cardio-vascular disease&#xD;
&#xD;
          -  Be willing to comply with study protocol&#xD;
&#xD;
          -  Provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lumason™ is contraindicated in subjects known to have right-to-left shunts, severe&#xD;
             pulmonary hypertension (pulmonary artery pressure &gt;90 mmHg), uncontrolled systemic&#xD;
             hypertension, and in subjects with adult respiratory distress syndrome.&#xD;
&#xD;
          -  Lumason™ should not be used in combination with dobutamine in subjects with conditions&#xD;
             suggesting cardiovascular instability where dobutamine is contraindicated.&#xD;
&#xD;
          -  Lumason™ should not be used in subjects with known hypersensitivity to the following&#xD;
             substances:&#xD;
&#xD;
               1. Macrogol 4000&#xD;
&#xD;
               2. Distearoylphosphatidylcholine&#xD;
&#xD;
               3. Dipalmitoylphosphatidylglycerol&#xD;
&#xD;
               4. Sodium Palmitic acid&#xD;
&#xD;
          -  Female who is pregnant or a nursing mother (the possibility of pregnancy has to be&#xD;
             excluded by negative serum or urine HCG results, obtained within 24 hours before&#xD;
             Lumason™ administration, or on the basis patient history, e.g.: tubal ligation,&#xD;
             hysterectomy, or a minimum of 1 year history without menses&#xD;
&#xD;
          -  Contraindications to MRI, pregnancy, lactation, morbid obesity, and severe&#xD;
             claustrophobia&#xD;
&#xD;
          -  Known allergy to gadolinium&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David S Liebeskind, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UCLA Medical Center</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>March 2019</verification_date>
  <study_first_submitted>September 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 28, 2017</study_first_posted>
  <last_update_submitted>March 22, 2019</last_update_submitted>
  <last_update_submitted_qc>March 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 26, 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>David Liebeskind</investigator_full_name>
    <investigator_title>Professor of Neurology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No plans to share any IPD with other researchers</ipd_description>
  </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/NCT03296852
org study id: 16-001538
nct id: NCT03296852
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: Yes
is unapproved device: Yes
is us export: No
The purpose of this research study is to test a new medical device, called SONAS. The SONAS
      device is a portable, battery-powered ultrasound device to detect strokes in the prehospital
      environment, such as emergency vehicles (eg. ambulances, helicopters). To demonstrate the
      safety of the device the goal is test it in a small number of healthy volunteers first.

      The SONAS device will be used to detect changes in blood flow to the brain through
      ultrasound, otherwise known as TransCranial Doppler (TCD). To date, the SONAS device has been
      tested extensively in the laboratory, in animals and in human cadavers. The purpose of the
      present study is to test the device for safety and efficacy in a small group of healthy
      volunteers. This study will test the device on 10 healthy volunteers. Each volunteer will
      have a physical examination, neurological examination, and brain MRI both before and after
      the TCD test is performed. All of these study procedures will be performed on 1 visit,
      lasting approximately 5 hours. The brain MRI's will be used to verify the effectiveness of
      the SONAS device on detecting changes in blood flow to the brain.
Specific Aims: Indicate the purpose of the research, specifying the problems and/or
      hypotheses to be addressed.

      Aim 1: Determine safety of the SONAS device Aim 1a: Obtain perfusion MRI (PWI) / quantitative
      MRI Aim 1b: Obtain MRI with gadolinium (gdMRI) Aim 2: Determine feasibility to detect
      microbubble specific frequencies

      Research Design and Methods: Describe in detail the design and methodology of the study.

      Since this is a 'first in human' study, testing primarily for the overall safety of the
      diagnostic approach, the aim is to enroll only healthy volunteers (e.g. no
      cerebro-/cardio-vascular history, no vascular risk factors etc.) into the study. We
      anticipate a total number of N=10 volunteers to be sufficient for this study.

      Step 1 After written informed consent and prior to the SONAS ultrasound study each volunteer
      will undergo a baseline assessment in form of a physical exam, including vital signs,
      National Institute of Health Stroke Scale (NIHSS) assessment and Modified Ranking Scale as
      well as the assessment of the Medical History.

      Step 2 Next, the volunteer will undergo a cranial MRI study. The MRI study will include a
      perfusion-weighted sequence to assess a baseline value for brain perfusion as well as
      gadolinium-enhanced T1-weighted images to assess the integrity of the blood-brain barrier.

      Step 3

      After the MRI study, the volunteer will undergo the SONAS ultrasound study. The study will be
      performed in supine position:

      Two ultrasound transducers/probes will be positioned on both sides of the volunteer's head at
      the temporal bone (above and in front of the ear on each side). To hold the
      transducers/probes in place a customized headset has been designed which is easy to use and
      comforting for the proband.

      Step 4 An IV line will be placed in a cubital or forearm vein. To assess a baseline value,
      ultrasound will be transmitted following an automated protocol to increase subsequently the
      output voltage from 5 volts to 50 volts. At each voltage step the received signals will be
      acquired and stored. Once the maximum output voltage of 50 Volts has been reached an
      additional 10 ultrasound pulses will be transmitted and the received data acquired. The total
      duration of this first data acquisition is 20 seconds.

      Step 5 A bolus of 1.0ml of the ultrasound contrast agent (so called 'Microbubbles') Lumason™,
      internationally known as SonoVue (Bracco Pharmaceuticals, Italy), will be injected into the
      IV line, followed by a 5.0ml IV bolus injection of saline. Lumason™ has been FDA approved for
      cardiac applications to opacify the left ventricular chamber and to improve the delineation
      of the left ventricular endocardial border. In the context of the present study Lumason™
      would be used off-label.

      Step 6 Following the IV bolus injection of Lumason™, ultrasound will be transmitted and
      received signals acquired following the same protocol as detailed under Step 4.

      Step 7 3 -5 hours after the SONAS ultrasound study has been performed Step 1 and Step 2 will
      be repeated.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Device Feasibility
masking: None (Open Label)
measure: Blood brain barrier impairment by extravasation of Gadolinium into the brain tissue
time frame: 5 hours
description: BBB impairment will be assessed by extravasation of Gadolinium into the brain tissue. Because of its molecular weight Gadolinium cannot enter the extravascular space, unless the BBB integrity is impaired. BBB impairment causes leakage of Gadolinium in into the extravascular space which, in turn, can be visualized by T1-weighted sequences.
arm group label: Healthy Volunteers
arm group type: Experimental
intervention type: Diagnostic Test
intervention name: SONAS Ultrasound Device
description: To assess a baseline value, ultrasound will be transmitted following an automated protocol to increase subsequently the output voltage from 5 volts to 50 volts. At each voltage step the received signals will be acquired and stored. Once the maximum output voltage of 50 Volts has been reached an additional 10 ultrasound pulses will be transmitted and the received data acquired. The total duration of this first data acquisition is 20 seconds. Following the IV bolus injection of Lumason™, ultrasound will be transmitted and received signals acquired following the same protocol as before.
arm group label: Healthy Volunteers
intervention type: Drug
intervention name: Lumason
description: An IV line will be placed in a cubital or forearm vein. A bolus of 1.0ml of the ultrasound contrast agent (so called 'Microbubbles') Lumason™, internationally known as SonoVue (Bracco Pharmaceuticals, Italy), will be injected into the IV line, followed by a 5.0ml IV bolus injection of saline. Lumason™ has been FDA approved for cardiac applications to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border. In the context of the present study Lumason™ would be used off-label.
arm group label: Healthy Volunteers
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: David S Liebeskind, 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: David Liebeskind
investigator title: Professor of Neurology
mesh term: Stroke
sharing ipd: No
ipd description: No plans to share any IPD with other researchers