<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/NCT04485208</url>
  </required_header>
  <id_info>
    <org_study_id>fUS_NeuropathicPain</org_study_id>
    <nct_id>NCT04485208</nct_id>
  </id_info>
  <brief_title>Focused Ultrasound for the Treatment of Neuropathic Pain</brief_title>
  <official_title>Open Label Study for the Use of Focused Transcranial Ultrasound for Treatment of Neuropathic Pain</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>
      A possible treatment approach for neuropathic pain would employ a process designed to promote&#xD;
      healthier function of the ventral posteromedial (VPM) and ventral posterolateral (VPL)&#xD;
      thalamic nuclei. This study is designed to employ focused ultrasound technology to target the&#xD;
      VPM and VPL thalamus among participants with ongoing neuropathic pain syndromes to evaluate&#xD;
      for tolerability and early efficacy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The present open-label study is being undertaken to evaluate focused transcranial ultrasound&#xD;
      therapy as an intervention for patients with neuropathic pain. The subjects in this research&#xD;
      study will be recruited through medical practice. Participants who are enrolled will undergo&#xD;
      8 consecutive weekly ultrasound sessions. Targeting for treatment will be based on patient&#xD;
      MRI scans using stereotaxic techniques.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">June 30, 2020</start_date>
  <completion_date type="Anticipated">December 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">June 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>Brief Pain Inventory (BPI)</measure>
    <time_frame>Baseline</time_frame>
    <description>Self-report measure containing a composite pain score and functional interference score. The pain subscale contains 4 questions, each with answers ranging from 0 'no pain' to 10 'pain as bad as you can imagine.' Total possible score for the pain subscale is 40 points. The functional/interference subscale contains 7 questions, with each answer ranging from 0 'does not interfere' to 10 'completely interferes.' The maximum possible score for the interference subscale is 70 points. The total overall composite BPI score is out of 100 maximum points. A clinical improvement is considered a decrease in BPI overall composite score by at least 30% from baseline.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Numeric Pain Rating Scale (NPRS)</measure>
    <time_frame>Baseline</time_frame>
    <description>The NRPS is a unidimensional measure of pain intensity for adults. The 11-point numeric scale ranges from '0' representing 'no pain' to 10 representing 'worst possible pain.' The NPRS can be administered verbally or graphically for self-completion. The respondent is asked to indicate the numeric scale value that best describes the intensity of their pain within the last 24-hours. Clinical improvement is denoted by at least 3 points improvement.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Patient Health Questionnaire (PHQ-9)</measure>
    <time_frame>Baseline</time_frame>
    <description>The PHQ-9 is a 9-item, self-report questionnaire to evaluate for depressive symptoms. Each question asks the patient if they have experienced a particular depressive symptom over the past two weeks. Answers may range from &quot;0&quot; (not at all), &quot;1&quot; (several days/week), &quot;2&quot; (more than half of the days), and &quot;3&quot; (nearly every day). Maximum total score is 27 points. A higher score indicates more severe depressive symptoms. A reduction in total score by at least 30% is considered clinically meaningful.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Brief Pain Inventory (BPI)</measure>
    <time_frame>Post Final Treatment (8 weeks from baseline)</time_frame>
    <description>Self-report measure containing a composite pain score and functional interference score. The pain subscale contains 4 questions, each with answers ranging from 0 'no pain' to 10 'pain as bad as you can imagine.' Total possible score for the pain subscale is 40 points. The functional/interference subscale contains 7 questions, with each answer ranging from 0 'does not interfere' to 10 'completely interferes.' The maximum possible score for the interference subscale is 70 points. The total overall composite BPI score is out of 100 maximum points. A clinical improvement is considered a decrease in BPI overall composite score by at least 30% from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numeric Pain Rating Scale (NPRS)</measure>
    <time_frame>Post Final Treatment (8 weeks from baseline)</time_frame>
    <description>The NRPS is a unidimensional measure of pain intensity for adults. The 11-point numeric scale ranges from '0' representing 'no pain' to 10 representing 'worst possible pain.' The NPRS can be administered verbally or graphically for self-completion. The respondent is asked to indicate the numeric scale value that best describes the intensity of their pain within the last 24-hours. Clinical improvement is denoted by at least 3 points improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Health Questionnaire (PHQ-9)</measure>
    <time_frame>Post Final Treatment (8 weeks from baseline)</time_frame>
    <description>The PHQ-9 is a 9-item, self-report questionnaire to evaluate for depressive symptoms. Each question asks the patient if they have experienced a particular depressive symptom over the past two weeks. Answers may range from &quot;0&quot; (not at all), &quot;1&quot; (several days/week), &quot;2&quot; (more than half of the days), and &quot;3&quot; (nearly every day). Maximum total score is 27 points. A higher score indicates more severe depressive symptoms. A reduction in total score by at least 30% is considered clinically meaningful.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Neuropathic Pain</condition>
  <arm_group>
    <arm_group_label>Active</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will undergo ten to thirty minutes of transcranial ultrasound treatment. The sonification device will be aimed at the thalamus. Targeting will include reference to scalp fiducials based on the obtained MRI; confirmation of target accuracy will either be obtained by Doppler waveform confirmation or optical tracking technology which co-registers patient neuroimaging with real space.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Focused Ultrasound</intervention_name>
    <description>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 Pulsar 1002 ultrasound device to track a patient's brain in virtual space as well as their physical location, thereby ensuring accurate placement.</description>
    <arm_group_label>Active</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  History of neuropathic pain (onset, location, intensity, duration, quality,&#xD;
             aggravating factors)&#xD;
&#xD;
          -  Confirmation of nervous system injury through imaging or negative or positive sensory&#xD;
             signs confined to the corresponding bodily area&#xD;
&#xD;
          -  Failure from at least 3 pharmacological treatments (e.g., antidepressants,&#xD;
             anticonvulsants, opioids)&#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&#xD;
&#xD;
          -  Pregnancy, women who may become pregnant or are breastfeeding&#xD;
&#xD;
          -  Subjects with scalp rash or open wounds on the scalp (for example from treatment of&#xD;
             squamous cell cancer)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</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_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Cohen SP, Mao J. Neuropathic pain: mechanisms and their clinical implications. BMJ. 2014 Feb 5;348:f7656. doi: 10.1136/bmj.f7656. Erratum In: BMJ. 2014;348:g2323.</citation>
    <PMID>24500412</PMID>
  </reference>
  <reference>
    <citation>Jang SH, Kim J, Lee HD. Delayed-onset central poststroke pain due to degeneration of the spinothalamic tract following thalamic hemorrhage: A case report. Medicine (Baltimore). 2018 Dec;97(50):e13533. doi: 10.1097/MD.0000000000013533.</citation>
    <PMID>30558012</PMID>
  </reference>
  <reference>
    <citation>Klit H, Finnerup NB, Jensen TS. Central post-stroke pain: clinical characteristics, pathophysiology, and management. Lancet Neurol. 2009 Sep;8(9):857-68. doi: 10.1016/S1474-4422(09)70176-0.</citation>
    <PMID>19679277</PMID>
  </reference>
  <reference>
    <citation>Kramer PR, Strand J, Stinson C, Bellinger LL, Kinchington PR, Yee MB, Umorin M, Peng YB. Role for the Ventral Posterior Medial/Posterior Lateral Thalamus and Anterior Cingulate Cortex in Affective/Motivation Pain Induced by Varicella Zoster Virus. Front Integr Neurosci. 2017 Oct 16;11:27. doi: 10.3389/fnint.2017.00027. eCollection 2017.</citation>
    <PMID>29089872</PMID>
  </reference>
  <reference>
    <citation>Krause T, Brunecker P, Pittl S, Taskin B, Laubisch D, Winter B, Lentza ME, Malzahn U, Villringer K, Villringer A, Jungehulsing GJ. Thalamic sensory strokes with and without pain: differences in lesion patterns in the ventral posterior thalamus. J Neurol Neurosurg Psychiatry. 2012 Aug;83(8):776-84. doi: 10.1136/jnnp-2011-301936. Epub 2012 Jun 13.</citation>
    <PMID>22696587</PMID>
  </reference>
  <reference>
    <citation>Mauguiere F, Desmedt JE. Thalamic pain syndrome of Dejerine-Roussy. Differentiation of four subtypes assisted by somatosensory evoked potentials data. Arch Neurol. 1988 Dec;45(12):1312-20. doi: 10.1001/archneur.1988.00520360030007.</citation>
    <PMID>3196191</PMID>
  </reference>
  <reference>
    <citation>Plotkin JL, Goldberg JA. Thinking Outside the Box (and Arrow): Current Themes in Striatal Dysfunction in Movement Disorders. Neuroscientist. 2019 Aug;25(4):359-379. doi: 10.1177/1073858418807887. Epub 2018 Oct 31.</citation>
    <PMID>30379121</PMID>
  </reference>
  <reference>
    <citation>Vartiainen N, Perchet C, Magnin M, Creac'h C, Convers P, Nighoghossian N, Mauguiere F, Peyron R, Garcia-Larrea L. Thalamic pain: anatomical and physiological indices of prediction. Brain. 2016 Mar;139(Pt 3):708-22. doi: 10.1093/brain/awv389. Epub 2016 Feb 8.</citation>
    <PMID>26912644</PMID>
  </reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 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>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuralgia</mesh_term>
  </condition_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/NCT04485208
org study id: fUS_NeuropathicPain
nct id: NCT04485208
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
A possible treatment approach for neuropathic pain would employ a process designed to promote
      healthier function of the ventral posteromedial (VPM) and ventral posterolateral (VPL)
      thalamic nuclei. This study is designed to employ focused ultrasound technology to target the
      VPM and VPL thalamus among participants with ongoing neuropathic pain syndromes to evaluate
      for tolerability and early efficacy.
The present open-label study is being undertaken to evaluate focused transcranial ultrasound
      therapy as an intervention for patients with neuropathic pain. The subjects in this research
      study will be recruited through medical practice. Participants who are enrolled will undergo
      8 consecutive weekly ultrasound sessions. Targeting for treatment will be based on patient
      MRI scans using stereotaxic techniques.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Brief Pain Inventory (BPI)
time frame: Baseline
description: Self-report measure containing a composite pain score and functional interference score. The pain subscale contains 4 questions, each with answers ranging from 0 'no pain' to 10 'pain as bad as you can imagine.' Total possible score for the pain subscale is 40 points. The functional/interference subscale contains 7 questions, with each answer ranging from 0 'does not interfere' to 10 'completely interferes.' The maximum possible score for the interference subscale is 70 points. The total overall composite BPI score is out of 100 maximum points. A clinical improvement is considered a decrease in BPI overall composite score by at least 30% from baseline.
measure: Numeric Pain Rating Scale (NPRS)
time frame: Baseline
description: The NRPS is a unidimensional measure of pain intensity for adults. The 11-point numeric scale ranges from '0' representing 'no pain' to 10 representing 'worst possible pain.' The NPRS can be administered verbally or graphically for self-completion. The respondent is asked to indicate the numeric scale value that best describes the intensity of their pain within the last 24-hours. Clinical improvement is denoted by at least 3 points improvement.
measure: Patient Health Questionnaire (PHQ-9)
time frame: Baseline
description: The PHQ-9 is a 9-item, self-report questionnaire to evaluate for depressive symptoms. Each question asks the patient if they have experienced a particular depressive symptom over the past two weeks. Answers may range from "0" (not at all), "1" (several days/week), "2" (more than half of the days), and "3" (nearly every day). Maximum total score is 27 points. A higher score indicates more severe depressive symptoms. A reduction in total score by at least 30% is considered clinically meaningful.
measure: Brief Pain Inventory (BPI)
time frame: Post Final Treatment (8 weeks from baseline)
description: Self-report measure containing a composite pain score and functional interference score. The pain subscale contains 4 questions, each with answers ranging from 0 'no pain' to 10 'pain as bad as you can imagine.' Total possible score for the pain subscale is 40 points. The functional/interference subscale contains 7 questions, with each answer ranging from 0 'does not interfere' to 10 'completely interferes.' The maximum possible score for the interference subscale is 70 points. The total overall composite BPI score is out of 100 maximum points. A clinical improvement is considered a decrease in BPI overall composite score by at least 30% from baseline.
measure: Numeric Pain Rating Scale (NPRS)
time frame: Post Final Treatment (8 weeks from baseline)
description: The NRPS is a unidimensional measure of pain intensity for adults. The 11-point numeric scale ranges from '0' representing 'no pain' to 10 representing 'worst possible pain.' The NPRS can be administered verbally or graphically for self-completion. The respondent is asked to indicate the numeric scale value that best describes the intensity of their pain within the last 24-hours. Clinical improvement is denoted by at least 3 points improvement.
measure: Patient Health Questionnaire (PHQ-9)
time frame: Post Final Treatment (8 weeks from baseline)
description: The PHQ-9 is a 9-item, self-report questionnaire to evaluate for depressive symptoms. Each question asks the patient if they have experienced a particular depressive symptom over the past two weeks. Answers may range from "0" (not at all), "1" (several days/week), "2" (more than half of the days), and "3" (nearly every day). Maximum total score is 27 points. A higher score indicates more severe depressive symptoms. A reduction in total score by at least 30% is considered clinically meaningful.
arm group label: Active
arm group type: Experimental
description: Patients will undergo ten to thirty minutes of transcranial ultrasound treatment. The sonification device will be aimed at the thalamus. Targeting will include reference to scalp fiducials based on the obtained MRI; confirmation of target accuracy will either be obtained by Doppler waveform confirmation or optical tracking technology which co-registers patient neuroimaging with real space.
intervention type: Device
intervention name: Focused Ultrasound
description: 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 Pulsar 1002 ultrasound device to track a patient's brain in virtual space as well as their physical location, thereby ensuring accurate placement.
arm group label: Active
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sheldon Jordan, MD
role: Principal Investigator
affiliation: Neurological Associates of West Los Angeles
facility: 
country: United States
citation: Cohen SP, Mao J. Neuropathic pain: mechanisms and their clinical implications. BMJ. 2014 Feb 5;348:f7656. doi: 10.1136/bmj.f7656. Erratum In: BMJ. 2014;348:g2323.
PMID: 24500412
citation: Jang SH, Kim J, Lee HD. Delayed-onset central poststroke pain due to degeneration of the spinothalamic tract following thalamic hemorrhage: A case report. Medicine (Baltimore). 2018 Dec;97(50):e13533. doi: 10.1097/MD.0000000000013533.
PMID: 30558012
citation: Klit H, Finnerup NB, Jensen TS. Central post-stroke pain: clinical characteristics, pathophysiology, and management. Lancet Neurol. 2009 Sep;8(9):857-68. doi: 10.1016/S1474-4422(09)70176-0.
PMID: 19679277
citation: Kramer PR, Strand J, Stinson C, Bellinger LL, Kinchington PR, Yee MB, Umorin M, Peng YB. Role for the Ventral Posterior Medial/Posterior Lateral Thalamus and Anterior Cingulate Cortex in Affective/Motivation Pain Induced by Varicella Zoster Virus. Front Integr Neurosci. 2017 Oct 16;11:27. doi: 10.3389/fnint.2017.00027. eCollection 2017.
PMID: 29089872
citation: Krause T, Brunecker P, Pittl S, Taskin B, Laubisch D, Winter B, Lentza ME, Malzahn U, Villringer K, Villringer A, Jungehulsing GJ. Thalamic sensory strokes with and without pain: differences in lesion patterns in the ventral posterior thalamus. J Neurol Neurosurg Psychiatry. 2012 Aug;83(8):776-84. doi: 10.1136/jnnp-2011-301936. Epub 2012 Jun 13.
PMID: 22696587
citation: Mauguiere F, Desmedt JE. Thalamic pain syndrome of Dejerine-Roussy. Differentiation of four subtypes assisted by somatosensory evoked potentials data. Arch Neurol. 1988 Dec;45(12):1312-20. doi: 10.1001/archneur.1988.00520360030007.
PMID: 3196191
citation: Plotkin JL, Goldberg JA. Thinking Outside the Box (and Arrow): Current Themes in Striatal Dysfunction in Movement Disorders. Neuroscientist. 2019 Aug;25(4):359-379. doi: 10.1177/1073858418807887. Epub 2018 Oct 31.
PMID: 30379121
citation: Vartiainen N, Perchet C, Magnin M, Creac'h C, Convers P, Nighoghossian N, Mauguiere F, Peyron R, Garcia-Larrea L. Thalamic pain: anatomical and physiological indices of prediction. Brain. 2016 Mar;139(Pt 3):708-22. doi: 10.1093/brain/awv389. Epub 2016 Feb 8.
PMID: 26912644
responsible party type: Sponsor
mesh term: Neuralgia
sharing ipd: No