<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/NCT03811405</url>
  </required_header>
  <id_info>
    <org_study_id>IRB201802397 -N -A</org_study_id>
    <secondary_id>OCR19607</secondary_id>
    <secondary_id>5R25NS108939-04</secondary_id>
    <secondary_id>MEDTRONIC INC</secondary_id>
    <nct_id>NCT03811405</nct_id>
  </id_info>
  <brief_title>Physiology, Imaging and Modeling of Essential Tremor</brief_title>
  <official_title>Physiology, Imaging and Modeling of Deep Brain Stimulation for Essential Tremor</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Neurological Disorders and Stroke (NINDS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medtronic</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Florida</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This project aims to investigate novel ways to deliver brain stimulation to Essential Tremor&#xD;
      (ET) patients by introducing software changes to their existing devices. The study team aims&#xD;
      to investigate safety and efficacy of these new stimulation parameters in patients with ET.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Deep brain stimulation (DBS) is a neuromodulatory therapy that is effective in a subset of&#xD;
      well selected essential tremor (ET) patients. However, as many as 1/5 of patients may&#xD;
      initially improve, but then steadily worsen following the operation. The investigators&#xD;
      developed a technique to study a variety of alternative stimulation methods without the use&#xD;
      of an invasive repeat surgical intervention.&#xD;
&#xD;
      The electrophysiological effects of non-conventional DBS differ from traditional DBS, however&#xD;
      the physiological differences in the setting of human tremor remain largely unknown. This&#xD;
      study plans to explore gaps in knowledge of neuromodulation and will collect and contribute&#xD;
      essential information to the underlying mechanism of action of DBS. The hypothesis of this&#xD;
      project centers around active biphasic stimulation providing a wider therapeutic window and a&#xD;
      lower adverse event profile as compared to conventional DBS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 1, 2021</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 30, 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>
    <intervention_model_description>Patients with chronically implanted DBS devices for ET who experience progressive worsening of tremor symptoms over time.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Each of the 3 interventions will be videotaped for blinded motor score assessment by an independent rater.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Volume of tissue activated from stimulation with ET DBS</measure>
    <time_frame>up to 24 hours</time_frame>
    <description>The study team will use computer simulation and virtual reconstruction of the brain from pre-operative MRI data to calculate the volume of tissue activated (VTA) from the novel stimulation patterns. The investigators will assess the feasibility of the patterns to address the worsening of ET that may occur in 20% or more of the ET population.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Baseline DBS settings versus active biphasic pulse DBS settings</measure>
    <time_frame>up to 1 hour</time_frame>
    <description>The investigators will compare the degree of tremor suppression from the most optimal DBS settings that can be obtained via traditional programming methods versus active biphasic DBS. The degree of tremor will be quantified by multiple clinical metrics including the Fahn-Tolosa-Marin Tremor Rating Scale and Kinesia ONE® accelerometer system.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Fahn-Tolosa-Marin Tremor Rating Scale</measure>
    <time_frame>up to 15 minutes</time_frame>
    <description>Essential tremor severity will be assessed by the clinically validated Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS). It is a 0 to 4 scale (0 = no tremor; 4 = severe amplitude of tremor) of 9 different parts of the body. The FTMTRS will be assessed for the various DBS settings.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tremor motor physiology</measure>
    <time_frame>up to 15 minutes</time_frame>
    <description>Essential tremor motor physiology will be recorded by the Kinesia ONE accelerometer system. THe Kinesia ONE system is a wireless wearable motion sensor unit and portable transducer that translates the degree of movement into a standardized scale. Tremor physiology will be assessed for the various DBS settings.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gait impairment</measure>
    <time_frame>up to 15 minutes</time_frame>
    <description>Essential tremor's effect on gait will be assessed by the GAITRite system. Patients will walk along a GAITRite floor mat to have the various gait parameters such as step time, cycle time, step length, stride length, etc measured. Gait parameters will be assessed on the various DBS settings.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Essential Tremor</condition>
  <condition>Parkinson Disease</condition>
  <condition>Dystonia</condition>
  <arm_group>
    <arm_group_label>Patients with Essential Tremor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with chronically implanted DBS devices for ET who experience progressive worsening of tremor symptoms over time. The DBS implantable pulse generator (IPG) will be loaded with a temporary custom firmware to allow implementation of active biphasic pulse stimulation. The following random conditions will be applied: (1) Home Settings; (2) VIN Biphasic; (3) Stimulator Off. A 30-minute washout period will be applied between each of the random conditions. Therefore, each patient will serve as their own control.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Active biphasic pulse stimulation---Home Settings</intervention_name>
    <description>During this visit, the DBS implantable pulse generator (IPG) will be loaded with a temporary custom firmware to allow implementation of active biphasic pulse stimulation.</description>
    <arm_group_label>Patients with Essential Tremor</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Active biphasic pulse stimulation---VIN Biphasic</intervention_name>
    <description>During this visit, the DBS implantable pulse generator (IPG) will be loaded with a temporary custom firmware to allow implementation of active biphasic pulse stimulation.</description>
    <arm_group_label>Patients with Essential Tremor</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Active biphasic pulse stimulation---Stimulator Off</intervention_name>
    <description>During this visit, the DBS implantable pulse generator (IPG) will be loaded with a temporary custom firmware to allow implementation of active biphasic pulse stimulation.</description>
    <arm_group_label>Patients with Essential Tremor</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Existing unilateral or bilateral VIN DBS for ET, non-demented (MMSE&gt;24), and must have&#xD;
             a documented suboptimal tremor suppression on two successive visits (compared to the&#xD;
             baseline post-operative improvement at 6 months following ET DBS surgery). For&#xD;
             bilateral cases, the most affected tremor side will be studied.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No diagnosis of Essential Tremor&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Leonardo B Almeida, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Univeristy of Florida</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Leonardo B Almeida, MD</last_name>
    <phone>(352) 294-5400</phone>
    <email>Leonardo.BritodeAlmeida@neurology.ufl.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Joshua K Wong, MD</last_name>
    <phone>(352) 294-5400</phone>
    <email>joshua.wong@neurology.ufl.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>UF Health at the University of Florida</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>McKnight Brain Institute--Fixel Center for Neurological Diseases</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32611</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 22, 2019</study_first_posted>
  <last_update_submitted>June 13, 2023</last_update_submitted>
  <last_update_submitted_qc>June 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Deep Brain Stimulation (DBS)</keyword>
  <keyword>ventralis intermedius nucleus (VIN)</keyword>
  <keyword>implantable pulse generator (IPG)</keyword>
  <keyword>Diffusion Tensor Imaging (DTI)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
    <mesh_term>Dystonia</mesh_term>
    <mesh_term>Tremor</mesh_term>
    <mesh_term>Essential Tremor</mesh_term>
  </condition_browse>
  <!-- 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/NCT03811405
org study id: IRB201802397 -N -A
secondary id: OCR19607
secondary id: 5R25NS108939-04
secondary id: MEDTRONIC INC
nct id: NCT03811405
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
This project aims to investigate novel ways to deliver brain stimulation to Essential Tremor
      (ET) patients by introducing software changes to their existing devices. The study team aims
      to investigate safety and efficacy of these new stimulation parameters in patients with ET.
Deep brain stimulation (DBS) is a neuromodulatory therapy that is effective in a subset of
      well selected essential tremor (ET) patients. However, as many as 1/5 of patients may
      initially improve, but then steadily worsen following the operation. The investigators
      developed a technique to study a variety of alternative stimulation methods without the use
      of an invasive repeat surgical intervention.

      The electrophysiological effects of non-conventional DBS differ from traditional DBS, however
      the physiological differences in the setting of human tremor remain largely unknown. This
      study plans to explore gaps in knowledge of neuromodulation and will collect and contribute
      essential information to the underlying mechanism of action of DBS. The hypothesis of this
      project centers around active biphasic stimulation providing a wider therapeutic window and a
      lower adverse event profile as compared to conventional DBS.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Patients with chronically implanted DBS devices for ET who experience progressive worsening of tremor symptoms over time.
primary purpose: Treatment
masking: None (Open Label)
masking description: Each of the 3 interventions will be videotaped for blinded motor score assessment by an independent rater.
measure: Volume of tissue activated from stimulation with ET DBS
time frame: up to 24 hours
description: The study team will use computer simulation and virtual reconstruction of the brain from pre-operative MRI data to calculate the volume of tissue activated (VTA) from the novel stimulation patterns. The investigators will assess the feasibility of the patterns to address the worsening of ET that may occur in 20% or more of the ET population.
measure: Baseline DBS settings versus active biphasic pulse DBS settings
time frame: up to 1 hour
description: The investigators will compare the degree of tremor suppression from the most optimal DBS settings that can be obtained via traditional programming methods versus active biphasic DBS. The degree of tremor will be quantified by multiple clinical metrics including the Fahn-Tolosa-Marin Tremor Rating Scale and Kinesia ONE® accelerometer system.
measure: The Fahn-Tolosa-Marin Tremor Rating Scale
time frame: up to 15 minutes
description: Essential tremor severity will be assessed by the clinically validated Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS). It is a 0 to 4 scale (0 = no tremor; 4 = severe amplitude of tremor) of 9 different parts of the body. The FTMTRS will be assessed for the various DBS settings.
measure: Tremor motor physiology
time frame: up to 15 minutes
description: Essential tremor motor physiology will be recorded by the Kinesia ONE accelerometer system. THe Kinesia ONE system is a wireless wearable motion sensor unit and portable transducer that translates the degree of movement into a standardized scale. Tremor physiology will be assessed for the various DBS settings.
measure: Gait impairment
time frame: up to 15 minutes
description: Essential tremor's effect on gait will be assessed by the GAITRite system. Patients will walk along a GAITRite floor mat to have the various gait parameters such as step time, cycle time, step length, stride length, etc measured. Gait parameters will be assessed on the various DBS settings.
arm group label: Patients with Essential Tremor
arm group type: Experimental
description: Patients with chronically implanted DBS devices for ET who experience progressive worsening of tremor symptoms over time. The DBS implantable pulse generator (IPG) will be loaded with a temporary custom firmware to allow implementation of active biphasic pulse stimulation. The following random conditions will be applied: (1) Home Settings; (2) VIN Biphasic; (3) Stimulator Off. A 30-minute washout period will be applied between each of the random conditions. Therefore, each patient will serve as their own control.
intervention type: Device
intervention name: Active biphasic pulse stimulation---Home Settings
description: During this visit, the DBS implantable pulse generator (IPG) will be loaded with a temporary custom firmware to allow implementation of active biphasic pulse stimulation.
arm group label: Patients with Essential Tremor
intervention type: Device
intervention name: Active biphasic pulse stimulation---VIN Biphasic
description: During this visit, the DBS implantable pulse generator (IPG) will be loaded with a temporary custom firmware to allow implementation of active biphasic pulse stimulation.
arm group label: Patients with Essential Tremor
intervention type: Device
intervention name: Active biphasic pulse stimulation---Stimulator Off
description: During this visit, the DBS implantable pulse generator (IPG) will be loaded with a temporary custom firmware to allow implementation of active biphasic pulse stimulation.
arm group label: Patients with Essential Tremor
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Leonardo B Almeida, MD
role: Principal Investigator
affiliation: Univeristy of Florida
last name: Leonardo B Almeida, MD
phone: (352) 294-5400
email: Leonardo.BritodeAlmeida@neurology.ufl.edu
last name: Joshua K Wong, MD
phone: (352) 294-5400
email: joshua.wong@neurology.ufl.edu
facility: 
status: Recruiting
facility: 
status: Not yet recruiting
country: United States
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Dystonia
mesh term: Tremor
mesh term: Essential Tremor