<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/NCT03760406</url>
  </required_header>
  <id_info>
    <org_study_id>CHUBX 2018/32</org_study_id>
    <nct_id>NCT03760406</nct_id>
  </id_info>
  <brief_title>Optimization of VIM Targeting in Essential Tremor Surgery</brief_title>
  <acronym>Opti-VIM</acronym>
  <official_title>Optimization of VIM Targeting in Essential Tremor Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Bordeaux</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Bordeaux</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Deep brain stimulation (DBS) for essential tremor is based on the intermedius ventralis&#xD;
      nucleus of the thalamus (VIM) stimulation. This structure is however very difficult to&#xD;
      target, as it remains invisible on imaging. The current procedure based on awake surgery with&#xD;
      clinical and electrophysiological testings has several limitations that lead us to develop a&#xD;
      probabilistic model to locate precisely the target. This study aims to show that asleep DBS&#xD;
      surgery based on this new targeting method leads to at least the same clinical results than&#xD;
      the classical procedure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The intermedius ventralis nucleus of the thalamus (VIM), which represents the target for deep&#xD;
      brain stimulation (DBS) in essential tremor, still remains invisible on 1,5 tesla MRI (the&#xD;
      only magnetic field available for stereotactic surgery). The target coordinates currently&#xD;
      used are based on stereotactic atlases or mean coordinates from retrospective series. They&#xD;
      are so imprecise that intra-operative clinical testing and micro-electrode recordings are&#xD;
      mandatory to locate the exact position of the VIM. This procedure is long lasting, requires&#xD;
      that the patient is awake, and increases the risk of intracerebral haemorrhage and nosocomial&#xD;
      infections. Furthermore, some patients are not improved despite a DBS lead implanted in the&#xD;
      electrophysiologically and clinically defined target. To overcome these limitations,&#xD;
      investigators developed a probabilistic model based on data extracted from imaging of&#xD;
      patients with particularly good outcomes after DBS surgery. This machine-learning model&#xD;
      allows calculating to coordinates of the VIM according to the position of radio-anatomical&#xD;
      landmarks with a mean precision of 1,65mm.&#xD;
&#xD;
      The aim of this study is to validate this new targeting method on a prospective cohort of&#xD;
      patients. DBS surgery will be performed under general anaesthesia, without intra-operative&#xD;
      clinical and electrophysiological testing, with a surgical robot and under CT-scan guidance&#xD;
      (O-Arm ©).&#xD;
&#xD;
      Neurostimulation device programming will be performed as usual. Patients' tremor and quality&#xD;
      of life will be evaluated pre and post-operatively at 3 months, according to the&#xD;
      Fahn-Tolosa-Marin (FTM) scale and with an accelerometry recording (for tremor) and with the&#xD;
      mPDQ-39 scale for quality of life. Surgical complications and side effects related to&#xD;
      neurostimulation will be gathered all along the follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 18, 2018</start_date>
  <completion_date type="Anticipated">July 2023</completion_date>
  <primary_completion_date type="Anticipated">July 2023</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of Fahn-Tolosa-Marin (FTM) scale score</measure>
    <time_frame>Before and 3 month after DBS surgery</time_frame>
    <description>Scale global range : min=0 / max=160 Higher values represent worse tremor</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Accelerometry recordings : spectral analysis</measure>
    <time_frame>Before and 3 month after DBS surgery</time_frame>
    <description>Accelerometry recordings at the pre-inclusion visit and at 3 months after surgery in ON and OFF-stimulation conditions with spectral analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accelerometry recordings : calculation of the total accelerometry power</measure>
    <time_frame>Before and 3 month after DBS surgery</time_frame>
    <description>Accelerometry recordings at the pre-inclusion visit and at 3 months after surgery in ON and OFF-stimulation conditions with calculation of the total accelerometry power.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surgical complications</measure>
    <time_frame>Up to 3 month after DBS surgery</time_frame>
    <description>Onset of infection, hematoma or seizure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Device complications and dysfunction</measure>
    <time_frame>Up to 3 month after DBS surgery</time_frame>
    <description>rupture or displacement of electrode, pain at the stimulation box implantation site or along the subcutaneous cable if they require further intervention, infection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurostimulation-related side effects</measure>
    <time_frame>Up to 3 month after DBS surgery</time_frame>
    <description>Onset of dysarthria and ataxia assessed by the items 1 to 4 of the Scale for Assessment and Rating of Ataxia (SARA), ataxia assessed by a posturometry analysis, paresthesia, muscular contractions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life: change of modified Parkinson's Disease Questionnaire-39 (mPDQ-39) scale score</measure>
    <time_frame>Before and 3 month after DBS surgery</time_frame>
    <description>Adaptation of Parkinson's Disease Questionnaire-39 to essential tremor Scale global range : min=0 / max=156 Higher values represent worse Quality of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coordinates of active contacts</measure>
    <time_frame>3 month after DBS surgery</time_frame>
    <description>Coordinates of active contacts (i.e; the contact with the best effect on tremor without side effects) These coordinates (x, y, z) are obtained by merging the images of the 3-month postoperative scanner with the images of the preoperative MRI.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Essential Tremor</condition>
  <arm_group>
    <arm_group_label>Severe essential tremor treated by DBS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Opti-VIM targeting in DBS surgery</intervention_name>
    <description>DBS surgery will be performed under general anaesthesia, without intra-operative clinical and electrophysiological testing, with a surgical robot and under CT-scan guidance (O-Arm ©). The VIM coordinates will be calculated with the probabilistic model that have been developed.</description>
    <arm_group_label>Severe essential tremor treated by DBS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Severe essential tremor despite the optimal medical management&#xD;
&#xD;
          -  Age between 18 and 75 years&#xD;
&#xD;
          -  Normal MRI scan&#xD;
&#xD;
          -  Mattis Dementia Rating Scale (MDRS) score ≥ 130&#xD;
&#xD;
          -  Affiliation to the social security&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Depression (Beck Depression Inventory scale &gt; 20)&#xD;
&#xD;
          -  Contra-indication to surgery or general anesthesia&#xD;
&#xD;
          -  Cerebral atrophy on MRI scan&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Antoine BENARD, MD</last_name>
    <role>Study Chair</role>
    <affiliation>USMR CHU de Bordeaux</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU de Bordeaux</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospices Civils de Lyon</name>
      <address>
        <city>Bron</city>
        <zip>69500</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>November 26, 2018</study_first_submitted>
  <study_first_submitted_qc>November 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 30, 2018</study_first_posted>
  <last_update_submitted>May 10, 2023</last_update_submitted>
  <last_update_submitted_qc>May 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Essential Tremor</keyword>
  <keyword>Deep brain stimulation</keyword>
  <keyword>Ventro-intermediate nucleus of the thalamus</keyword>
  <keyword>Targeting</keyword>
  <keyword>Asleep surgery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT03760406
org study id: CHUBX 2018/32
nct id: NCT03760406
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Deep brain stimulation (DBS) for essential tremor is based on the intermedius ventralis
      nucleus of the thalamus (VIM) stimulation. This structure is however very difficult to
      target, as it remains invisible on imaging. The current procedure based on awake surgery with
      clinical and electrophysiological testings has several limitations that lead us to develop a
      probabilistic model to locate precisely the target. This study aims to show that asleep DBS
      surgery based on this new targeting method leads to at least the same clinical results than
      the classical procedure.
The intermedius ventralis nucleus of the thalamus (VIM), which represents the target for deep
      brain stimulation (DBS) in essential tremor, still remains invisible on 1,5 tesla MRI (the
      only magnetic field available for stereotactic surgery). The target coordinates currently
      used are based on stereotactic atlases or mean coordinates from retrospective series. They
      are so imprecise that intra-operative clinical testing and micro-electrode recordings are
      mandatory to locate the exact position of the VIM. This procedure is long lasting, requires
      that the patient is awake, and increases the risk of intracerebral haemorrhage and nosocomial
      infections. Furthermore, some patients are not improved despite a DBS lead implanted in the
      electrophysiologically and clinically defined target. To overcome these limitations,
      investigators developed a probabilistic model based on data extracted from imaging of
      patients with particularly good outcomes after DBS surgery. This machine-learning model
      allows calculating to coordinates of the VIM according to the position of radio-anatomical
      landmarks with a mean precision of 1,65mm.

      The aim of this study is to validate this new targeting method on a prospective cohort of
      patients. DBS surgery will be performed under general anaesthesia, without intra-operative
      clinical and electrophysiological testing, with a surgical robot and under CT-scan guidance
      (O-Arm ©).

      Neurostimulation device programming will be performed as usual. Patients' tremor and quality
      of life will be evaluated pre and post-operatively at 3 months, according to the
      Fahn-Tolosa-Marin (FTM) scale and with an accelerometry recording (for tremor) and with the
      mPDQ-39 scale for quality of life. Surgical complications and side effects related to
      neurostimulation will be gathered all along the follow-up.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change of Fahn-Tolosa-Marin (FTM) scale score
time frame: Before and 3 month after DBS surgery
description: Scale global range : min=0 / max=160 Higher values represent worse tremor
measure: Accelerometry recordings : spectral analysis
time frame: Before and 3 month after DBS surgery
description: Accelerometry recordings at the pre-inclusion visit and at 3 months after surgery in ON and OFF-stimulation conditions with spectral analysis.
measure: Accelerometry recordings : calculation of the total accelerometry power
time frame: Before and 3 month after DBS surgery
description: Accelerometry recordings at the pre-inclusion visit and at 3 months after surgery in ON and OFF-stimulation conditions with calculation of the total accelerometry power.
measure: Surgical complications
time frame: Up to 3 month after DBS surgery
description: Onset of infection, hematoma or seizure
measure: Device complications and dysfunction
time frame: Up to 3 month after DBS surgery
description: rupture or displacement of electrode, pain at the stimulation box implantation site or along the subcutaneous cable if they require further intervention, infection.
measure: Neurostimulation-related side effects
time frame: Up to 3 month after DBS surgery
description: Onset of dysarthria and ataxia assessed by the items 1 to 4 of the Scale for Assessment and Rating of Ataxia (SARA), ataxia assessed by a posturometry analysis, paresthesia, muscular contractions
measure: Quality of life: change of modified Parkinson's Disease Questionnaire-39 (mPDQ-39) scale score
time frame: Before and 3 month after DBS surgery
description: Adaptation of Parkinson's Disease Questionnaire-39 to essential tremor Scale global range : min=0 / max=156 Higher values represent worse Quality of life
measure: Coordinates of active contacts
time frame: 3 month after DBS surgery
description: Coordinates of active contacts (i.e; the contact with the best effect on tremor without side effects) These coordinates (x, y, z) are obtained by merging the images of the 3-month postoperative scanner with the images of the preoperative MRI.
arm group label: Severe essential tremor treated by DBS
arm group type: Experimental
intervention type: Procedure
intervention name: Opti-VIM targeting in DBS surgery
description: DBS surgery will be performed under general anaesthesia, without intra-operative clinical and electrophysiological testing, with a surgical robot and under CT-scan guidance (O-Arm ©). The VIM coordinates will be calculated with the probabilistic model that have been developed.
arm group label: Severe essential tremor treated by DBS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Antoine BENARD, MD
role: Study Chair
affiliation: USMR CHU de Bordeaux
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Tremor
mesh term: Essential Tremor