<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/NCT04497363</url>
  </required_header>
  <id_info>
    <org_study_id>fUS_ADHD</org_study_id>
    <nct_id>NCT04497363</nct_id>
  </id_info>
  <brief_title>Focused Ultrasound for the Treatment of ADHD Symptoms</brief_title>
  <official_title>Open Label Study for the Use of Transcranial Ultrasound Treatment of Attention Deficit Hyperactive Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Neurological Associates of West Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Neurological Associates of West Los Angeles</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this open label study is to evaluate longer term tolerability and potential&#xD;
      effectiveness of transcranial ultrasound in people with attention deficit hyperactive&#xD;
      disorder (ADHD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary cortical regions thought to be implicated in ADHD include the prefrontal,&#xD;
      orbitofrontal, and anterior cingulate cortices. A possible treatment approach for ADHD would&#xD;
      employ a process designed to promote healthier function of the anterior cingulate region. The&#xD;
      anterior cingulate in particular appears to be implicated in the activation of cognitive&#xD;
      control networks, and has been posited as an area of interest for therapeutic research on&#xD;
      ADHD. The subjects in this research study will be recruited through medical practice and&#xD;
      enrolled in an 8-week protocol to undergo 8 consecutive weekly ultrasound sessions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">March 2, 2026</completion_date>
  <primary_completion_date type="Anticipated">October 30, 2025</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adult ADHD Self-Report Scale (ASRS-v1.1)</measure>
    <time_frame>Baseline</time_frame>
    <description>This instrument is designed to evaluate for severity of symptoms as specified in the DSM-IV-TR. The ASRS is composed of 18 questions, and uses a scale that ranges from 0-4 based on the individuals mark in either the &quot;never, rarely, sometimes, often, very often&quot; column for a possible total score of 72. The minimum score to qualify for study inclusion is 8 (i.e., 4 or more &quot;symptom-positive&quot; answers), and the maximum possible score is 72. The higher the score, the more indicative of higher severity of ADHD symptoms. Each column is used to describe the severity of the individuals symptoms based on the questions asked. Each participant is asked to make a mark within one column for each question that best describes their answer. The first 6 questions of the scale comprise Part A, which is more generally used as a screening measure. Questions 12-18 comprise Part B, which provides further identifying clues for individual symptoms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adult ADHD Self-Report Scale (ASRS-v1.1)</measure>
    <time_frame>Post Final Treatment (8 weeks from baseline)</time_frame>
    <description>This instrument is designed to evaluate for severity of symptoms as specified in the DSM-IV-TR. The ASRS is composed of 18 questions, and uses a scale that ranges from 0-4 based on the individuals mark in either the &quot;never, rarely, sometimes, often, very often&quot; column for a possible total score of 72. The higher the score, the more indicative of higher severity of ADHD symptoms. Each column is used to describe the severity of the individuals symptoms based on the questions asked. Each participant is asked to make a mark within one column for each question that best describes their answer. The first 6 questions of the scale comprise Part A, which is more generally used as a screening measure. Questions 12-18 comprise Part B, which provides further identifying clues for individual symptoms. Improvement will be gauged by reduction in overall score (minimally clinically important difference will be 20% for this study).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>ADHD</condition>
  <arm_group>
    <arm_group_label>Focused Ultrasound</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>On the day of the ultrasound appointment, patients will undergo ten minutes of ultrasound targeting the anterior cingulate. The DWL Doppler ultrasound device enables visual and auditory waveform confirmation of the anterior cerebral artery, and optical tracking technology (e.g., AntNeuro Visor2™ system) may be used in tandem with the Brainsonix ultrasound device to track a patient's brain in virtual space as well as their physical location, thereby ensuring accurate placement.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Brainsonix Pulsar 1002</intervention_name>
    <description>Each participant will undergo 8 consecutive weekly sessions (each session is 10 minutes long) of focused ultrasound with the Brainsonix Pulsar 1002 device.</description>
    <arm_group_label>Focused Ultrasound</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of Attention Deficit Hyperactive Disorder (ADHD)&#xD;
&#xD;
          -  Failure to respond to traditional symptom management (e.g. stimulants,&#xD;
             psychoeducation, cognitive-behavior therapy, etc.)&#xD;
&#xD;
          -  Score of at least 8 (4 ADHD-positive items) on the Adult ADHD Self-Report&#xD;
             Questionnaire (ASRS-V1.1)&#xD;
&#xD;
          -  At least 18 years of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  • Subjects unable to give informed consent&#xD;
&#xD;
               -  Subjects who would not be able to lay down without excessive movement in a calm&#xD;
                  environment sufficiently long enough to be able to achieve sleep&#xD;
&#xD;
               -  Recent surgery or dental work within 3 months of the scheduled procedure.&#xD;
&#xD;
               -  Pregnancy, women who may become pregnant or are breastfeeding&#xD;
&#xD;
               -  Advanced terminal illness&#xD;
&#xD;
               -  Any active cancer or chemotherapy&#xD;
&#xD;
               -  Any other neoplastic illness or illness characterized by neovascularity&#xD;
&#xD;
               -  Macular degeneration&#xD;
&#xD;
               -  Subjects with scalp rash or open wounds on the scalp (for example from treatment&#xD;
                  of squamous cell cancer)&#xD;
&#xD;
               -  Advanced kidney, pulmonary, cardiac or liver failure&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sheldon Jordan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Neurological Associates of West Los Angeles</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Neurological Associates of West LA</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurological Associates of West Los Angele</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Bandelow B, Michaelis S. Epidemiology of anxiety disorders in the 21st century. Dialogues Clin Neurosci. 2015 Sep;17(3):327-35. doi: 10.31887/DCNS.2015.17.3/bbandelow.</citation>
    <PMID>26487813</PMID>
  </reference>
  <reference>
    <citation>Coupe P, Manjon JV, Lanuza E, Catheline G. Lifespan Changes of the Human Brain In Alzheimer's Disease. Sci Rep. 2019 Mar 8;9(1):3998. doi: 10.1038/s41598-019-39809-8.</citation>
    <PMID>30850617</PMID>
  </reference>
  <reference>
    <citation>Drevets WC, Savitz J, Trimble M. The subgenual anterior cingulate cortex in mood disorders. CNS Spectr. 2008 Aug;13(8):663-81. doi: 10.1017/s1092852900013754.</citation>
    <PMID>18704022</PMID>
  </reference>
  <reference>
    <citation>Mayberg HS, Brannan SK, Mahurin RK, Jerabek PA, Brickman JS, Tekell JL, Silva JA, McGinnis S, Glass TG, Martin CC, Fox PT. Cingulate function in depression: a potential predictor of treatment response. Neuroreport. 1997 Mar 3;8(4):1057-61. doi: 10.1097/00001756-199703030-00048.</citation>
    <PMID>9141092</PMID>
  </reference>
  <reference>
    <citation>Chan E, Fogler JM, Hammerness PG. Treatment of Attention-Deficit/Hyperactivity Disorder in Adolescents: A Systematic Review. JAMA. 2016 May 10;315(18):1997-2008. doi: 10.1001/jama.2016.5453.</citation>
    <PMID>27163988</PMID>
  </reference>
  <reference>
    <citation>Dunn GA, Nigg JT, Sullivan EL. Neuroinflammation as a risk factor for attention deficit hyperactivity disorder. Pharmacol Biochem Behav. 2019 Jul;182:22-34. doi: 10.1016/j.pbb.2019.05.005. Epub 2019 May 16.</citation>
    <PMID>31103523</PMID>
  </reference>
  <reference>
    <citation>Amico F, Stauber J, Koutsouleris N, Frodl T. Anterior cingulate cortex gray matter abnormalities in adults with attention deficit hyperactivity disorder: a voxel-based morphometry study. Psychiatry Res. 2011 Jan 30;191(1):31-5. doi: 10.1016/j.pscychresns.2010.08.011. Epub 2010 Dec 3.</citation>
    <PMID>21129938</PMID>
  </reference>
  <reference>
    <citation>Shaw P, Malek M, Watson B, Greenstein D, de Rossi P, Sharp W. Trajectories of cerebral cortical development in childhood and adolescence and adult attention-deficit/hyperactivity disorder. Biol Psychiatry. 2013 Oct 15;74(8):599-606. doi: 10.1016/j.biopsych.2013.04.007. Epub 2013 May 28.</citation>
    <PMID>23726514</PMID>
  </reference>
  <reference>
    <citation>Arnsten AF, Rubia K. Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: disruptions in neurodevelopmental psychiatric disorders. J Am Acad Child Adolesc Psychiatry. 2012 Apr;51(4):356-67. doi: 10.1016/j.jaac.2012.01.008. Epub 2012 Mar 3.</citation>
    <PMID>22449642</PMID>
  </reference>
  <reference>
    <citation>Materna L, Wiesner CD, Shushakova A, Trieloff J, Weber N, Engell A, Schubotz RI, Bauer J, Pedersen A, Ohrmann P. Adult patients with ADHD differ from healthy controls in implicit, but not explicit, emotion regulation. J Psychiatry Neurosci. 2019 Sep 1;44(5):340-349. doi: 10.1503/jpn.180139.</citation>
    <PMID>31025560</PMID>
  </reference>
  <reference>
    <citation>Tang C, Wei Y, Zhao J, Nie J. Different Developmental Pattern of Brain Activities in ADHD: A Study of Resting-State fMRI. Dev Neurosci. 2018;40(3):246-257. doi: 10.1159/000490289. Epub 2018 Jul 13.</citation>
    <PMID>30153660</PMID>
  </reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>September 26, 2022</last_update_submitted>
  <last_update_submitted_qc>September 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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/NCT04497363
org study id: fUS_ADHD
nct id: NCT04497363
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The purpose of this open label study is to evaluate longer term tolerability and potential
      effectiveness of transcranial ultrasound in people with attention deficit hyperactive
      disorder (ADHD).
The primary cortical regions thought to be implicated in ADHD include the prefrontal,
      orbitofrontal, and anterior cingulate cortices. A possible treatment approach for ADHD would
      employ a process designed to promote healthier function of the anterior cingulate region. The
      anterior cingulate in particular appears to be implicated in the activation of cognitive
      control networks, and has been posited as an area of interest for therapeutic research on
      ADHD. The subjects in this research study will be recruited through medical practice and
      enrolled in an 8-week protocol to undergo 8 consecutive weekly ultrasound sessions.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adult ADHD Self-Report Scale (ASRS-v1.1)
time frame: Baseline
description: This instrument is designed to evaluate for severity of symptoms as specified in the DSM-IV-TR. The ASRS is composed of 18 questions, and uses a scale that ranges from 0-4 based on the individuals mark in either the "never, rarely, sometimes, often, very often" column for a possible total score of 72. The minimum score to qualify for study inclusion is 8 (i.e., 4 or more "symptom-positive" answers), and the maximum possible score is 72. The higher the score, the more indicative of higher severity of ADHD symptoms. Each column is used to describe the severity of the individuals symptoms based on the questions asked. Each participant is asked to make a mark within one column for each question that best describes their answer. The first 6 questions of the scale comprise Part A, which is more generally used as a screening measure. Questions 12-18 comprise Part B, which provides further identifying clues for individual symptoms.
measure: Adult ADHD Self-Report Scale (ASRS-v1.1)
time frame: Post Final Treatment (8 weeks from baseline)
description: This instrument is designed to evaluate for severity of symptoms as specified in the DSM-IV-TR. The ASRS is composed of 18 questions, and uses a scale that ranges from 0-4 based on the individuals mark in either the "never, rarely, sometimes, often, very often" column for a possible total score of 72. The higher the score, the more indicative of higher severity of ADHD symptoms. Each column is used to describe the severity of the individuals symptoms based on the questions asked. Each participant is asked to make a mark within one column for each question that best describes their answer. The first 6 questions of the scale comprise Part A, which is more generally used as a screening measure. Questions 12-18 comprise Part B, which provides further identifying clues for individual symptoms. Improvement will be gauged by reduction in overall score (minimally clinically important difference will be 20% for this study).
arm group label: Focused Ultrasound
arm group type: Experimental
description: On the day of the ultrasound appointment, patients will undergo ten minutes of ultrasound targeting the anterior cingulate. The DWL Doppler ultrasound device enables visual and auditory waveform confirmation of the anterior cerebral artery, and optical tracking technology (e.g., AntNeuro Visor2™ system) may be used in tandem with the Brainsonix ultrasound device to track a patient's brain in virtual space as well as their physical location, thereby ensuring accurate placement.
intervention type: Device
intervention name: Brainsonix Pulsar 1002
description: Each participant will undergo 8 consecutive weekly sessions (each session is 10 minutes long) of focused ultrasound with the Brainsonix Pulsar 1002 device.
arm group label: Focused Ultrasound
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Sheldon Jordan, MD
role: Principal Investigator
affiliation: Neurological Associates of West Los Angeles
facility: 
facility: 
country: United States
citation: Bandelow B, Michaelis S. Epidemiology of anxiety disorders in the 21st century. Dialogues Clin Neurosci. 2015 Sep;17(3):327-35. doi: 10.31887/DCNS.2015.17.3/bbandelow.
PMID: 26487813
citation: Coupe P, Manjon JV, Lanuza E, Catheline G. Lifespan Changes of the Human Brain In Alzheimer's Disease. Sci Rep. 2019 Mar 8;9(1):3998. doi: 10.1038/s41598-019-39809-8.
PMID: 30850617
citation: Drevets WC, Savitz J, Trimble M. The subgenual anterior cingulate cortex in mood disorders. CNS Spectr. 2008 Aug;13(8):663-81. doi: 10.1017/s1092852900013754.
PMID: 18704022
citation: Mayberg HS, Brannan SK, Mahurin RK, Jerabek PA, Brickman JS, Tekell JL, Silva JA, McGinnis S, Glass TG, Martin CC, Fox PT. Cingulate function in depression: a potential predictor of treatment response. Neuroreport. 1997 Mar 3;8(4):1057-61. doi: 10.1097/00001756-199703030-00048.
PMID: 9141092
citation: Chan E, Fogler JM, Hammerness PG. Treatment of Attention-Deficit/Hyperactivity Disorder in Adolescents: A Systematic Review. JAMA. 2016 May 10;315(18):1997-2008. doi: 10.1001/jama.2016.5453.
PMID: 27163988
citation: Dunn GA, Nigg JT, Sullivan EL. Neuroinflammation as a risk factor for attention deficit hyperactivity disorder. Pharmacol Biochem Behav. 2019 Jul;182:22-34. doi: 10.1016/j.pbb.2019.05.005. Epub 2019 May 16.
PMID: 31103523
citation: Amico F, Stauber J, Koutsouleris N, Frodl T. Anterior cingulate cortex gray matter abnormalities in adults with attention deficit hyperactivity disorder: a voxel-based morphometry study. Psychiatry Res. 2011 Jan 30;191(1):31-5. doi: 10.1016/j.pscychresns.2010.08.011. Epub 2010 Dec 3.
PMID: 21129938
citation: Shaw P, Malek M, Watson B, Greenstein D, de Rossi P, Sharp W. Trajectories of cerebral cortical development in childhood and adolescence and adult attention-deficit/hyperactivity disorder. Biol Psychiatry. 2013 Oct 15;74(8):599-606. doi: 10.1016/j.biopsych.2013.04.007. Epub 2013 May 28.
PMID: 23726514
citation: Arnsten AF, Rubia K. Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: disruptions in neurodevelopmental psychiatric disorders. J Am Acad Child Adolesc Psychiatry. 2012 Apr;51(4):356-67. doi: 10.1016/j.jaac.2012.01.008. Epub 2012 Mar 3.
PMID: 22449642
citation: Materna L, Wiesner CD, Shushakova A, Trieloff J, Weber N, Engell A, Schubotz RI, Bauer J, Pedersen A, Ohrmann P. Adult patients with ADHD differ from healthy controls in implicit, but not explicit, emotion regulation. J Psychiatry Neurosci. 2019 Sep 1;44(5):340-349. doi: 10.1503/jpn.180139.
PMID: 31025560
citation: Tang C, Wei Y, Zhao J, Nie J. Different Developmental Pattern of Brain Activities in ADHD: A Study of Resting-State fMRI. Dev Neurosci. 2018;40(3):246-257. doi: 10.1159/000490289. Epub 2018 Jul 13.
PMID: 30153660
responsible party type: Sponsor
sharing ipd: No