<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/NCT02264925</url>
  </required_header>
  <id_info>
    <org_study_id>CHUBX 2013/15</org_study_id>
    <nct_id>NCT02264925</nct_id>
  </id_info>
  <brief_title>Thalamic LFPs and VIM DBS in Essential Tremor: Correlation, Evolution, and Therapeutic Perspectives</brief_title>
  <acronym>VIM-CLT</acronym>
  <official_title>Thalamic LFPs and VIM DBS in Essential Tremor: Correlation, Evolution, and Therapeutic Perspectives</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Bordeaux</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>APTES 100 rue boileau 69006 Lyon</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Bordeaux</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to characterize through spectral analysis intra-thalamic local&#xD;
      field potentials (LFPs) recorded through implanted DBS leads during periods with and without&#xD;
      tremor in patients suffering from severe essential tremor.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Essential tremor (ET) is one of the most common adult movement disorders with a prevalence of&#xD;
      4% in the general population. Although several medications (primidone, beta-adrenergic&#xD;
      blockers, benzodiazepines…) are commonly used, few of them are truly effective for&#xD;
      controlling the severe forms of ET. Since 1987, an alternative has emerged with the&#xD;
      development of high frequency deep brain stimulation (DBS) of the thalamic nucleus ventralis&#xD;
      intermedius (VIM). This surgical technique now represents the gold standard treatment for&#xD;
      tremor-disabled ET patients. Although VIM-DBS is clearly effective for treatment of essential&#xD;
      tremor (ET) a partial loss of DBS effectiveness may occur over time in some patients. This&#xD;
      loss of DBS effectiveness could be related to an adaptation of the local neuronal network to&#xD;
      chronic stimulation (changes in synaptic plasticity). In order to avoid this problem,&#xD;
      investigators plan to develop a intermittent mode of VIM stimulation using a new Medtronic&#xD;
      device combining a DBS system with local field potential (LFPs) sensing capability. First,&#xD;
      investigators propose to analyse VIM LFPs in order to define a tremor biomarker in 10&#xD;
      patients operated for severe ET. Thereafter, investigators will automatically detect this&#xD;
      biomarker using a specific algorithm and use it to trigger stimulation at the onset of tremor&#xD;
      only. Thus, this project will allow us to optimize DBS therapy in ET, by improving the&#xD;
      longevity of implantable devices and avoiding the loss of efficacy previously reported&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2014</start_date>
  <completion_date type="Actual">November 19, 2020</completion_date>
  <primary_completion_date type="Actual">November 19, 2020</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>LFPs records 3 month after implantation</measure>
    <time_frame>3 month after implantation</time_frame>
    <description>in order to characterize the features of tremor-related thalamic activity during the initiation of movement-related tremor-induced activity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>LFPs records 12 month after implantation</measure>
    <time_frame>12 month after implantation</time_frame>
    <description>in order to characterize the features of tremor-related thalamic activity during the initiation of movement-related tremor-induced activity</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Essential Tremor</condition>
  <arm_group>
    <arm_group_label>Deep Brain Stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All of included patients will receive a standard deep brain stimulation of the thalamus in order to reduce their essential tremor</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Deep Brain Stimulation with Medtronic Activa PC+S systems</intervention_name>
    <description>Deep Brain Stimulation of VIM.</description>
    <arm_group_label>Deep Brain Stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients suffering from severe and disabling ET with serious impact on their quality&#xD;
             of life (QoL).&#xD;
&#xD;
          -  18-70 years old&#xD;
&#xD;
          -  Free of evolutive and untreated psychiatric disorder&#xD;
&#xD;
          -  Tremor must be predominant in the upper limbs although it can affect the lower limbs,&#xD;
             head and voice.&#xD;
&#xD;
          -  Affiliation to a social security system&#xD;
&#xD;
          -  Written informed consent signed by the participant and the investigator (prior to any&#xD;
             examination required by research)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Parkinsonian tremor&#xD;
&#xD;
          -  Pregnancy or lactating women&#xD;
&#xD;
          -  Severe co-morbidity (cardiac, renal or respiratory failures, evolutive cancer)&#xD;
&#xD;
          -  Impaired cognitive functions (score &lt;130 on Mattis scale).&#xD;
&#xD;
          -  Patients with severe atrophy or lesions on MRI&#xD;
&#xD;
          -  Depression (Beck &gt; 10)&#xD;
&#xD;
          -  Participation in another clinical research for 18 months (after surgery)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>BURBAUD Pierre, MD-PhD</last_name>
    <role>Study Director</role>
    <affiliation>University Hospital Bordeaux, France</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nicolas LANGBOUR, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>IMN CNRS UMR 5293, Université Bordeaux 2 Segalen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Bordeaux, France</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Barbe MT, Liebhart L, Runge M, Pauls KA, Wojtecki L, Schnitzler A, Allert N, Fink GR, Sturm V, Maarouf M, Timmermann L. Deep brain stimulation in the nucleus ventralis intermedius in patients with essential tremor: habituation of tremor suppression. J Neurol. 2011 Mar;258(3):434-9. doi: 10.1007/s00415-010-5773-3. Epub 2010 Oct 8.</citation>
    <PMID>20927533</PMID>
  </reference>
  <reference>
    <citation>Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J. Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol. 1987;50(1-6):344-6. doi: 10.1159/000100803.</citation>
    <PMID>3329873</PMID>
  </reference>
  <reference>
    <citation>Blomstedt P, Hariz GM, Hariz MI, Koskinen LO. Thalamic deep brain stimulation in the treatment of essential tremor: a long-term follow-up. Br J Neurosurg. 2007 Oct;21(5):504-9. doi: 10.1080/02688690701552278.</citation>
    <PMID>17922323</PMID>
  </reference>
  <reference>
    <citation>Brown P, Williams D. Basal ganglia local field potential activity: character and functional significance in the human. Clin Neurophysiol. 2005 Nov;116(11):2510-9. doi: 10.1016/j.clinph.2005.05.009. Epub 2005 Jul 18.</citation>
    <PMID>16029963</PMID>
  </reference>
  <reference>
    <citation>Garcia Ruiz P, Muniz de Igneson J, Lopez Ferro O, Martin C, Magarinos Ascone C. Deep brain stimulation holidays in essential tremor. J Neurol. 2001 Aug;248(8):725-6. doi: 10.1007/s004150170127. No abstract available.</citation>
    <PMID>11569910</PMID>
  </reference>
  <reference>
    <citation>Hariz MI, Shamsgovara P, Johansson F, Hariz G, Fodstad H. Tolerance and tremor rebound following long-term chronic thalamic stimulation for Parkinsonian and essential tremor. Stereotact Funct Neurosurg. 1999;72(2-4):208-18. doi: 10.1159/000029728.</citation>
    <PMID>10853080</PMID>
  </reference>
  <reference>
    <citation>Limousin P, Speelman JD, Gielen F, Janssens M. Multicentre European study of thalamic stimulation in parkinsonian and essential tremor. J Neurol Neurosurg Psychiatry. 1999 Mar;66(3):289-96. doi: 10.1136/jnnp.66.3.289.</citation>
    <PMID>10084526</PMID>
  </reference>
  <reference>
    <citation>Schuurman PR, Bosch DA, Bossuyt PM, Bonsel GJ, van Someren EJ, de Bie RM, Merkus MP, Speelman JD. A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor. N Engl J Med. 2000 Feb 17;342(7):461-8. doi: 10.1056/NEJM200002173420703.</citation>
    <PMID>10675426</PMID>
  </reference>
  <reference>
    <citation>Stacy MA, Elble RJ, Ondo WG, Wu SC, Hulihan J; TRS study group. Assessment of interrater and intrarater reliability of the Fahn-Tolosa-Marin Tremor Rating Scale in essential tremor. Mov Disord. 2007 Apr 30;22(6):833-8. doi: 10.1002/mds.21412.</citation>
    <PMID>17343274</PMID>
  </reference>
  <reference>
    <citation>Yoshida F, Martinez-Torres I, Pogosyan A, Holl E, Petersen E, Chen CC, Foltynie T, Limousin P, Zrinzo LU, Hariz MI, Brown P. Value of subthalamic nucleus local field potentials recordings in predicting stimulation parameters for deep brain stimulation in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2010 Aug;81(8):885-9. doi: 10.1136/jnnp.2009.190918. Epub 2010 May 12.</citation>
    <PMID>20466699</PMID>
  </reference>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>June 20, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <last_update_submitted>August 6, 2021</last_update_submitted>
  <last_update_submitted_qc>August 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Essential tremor</keyword>
  <keyword>Deep brain stimulation (DBS)</keyword>
  <keyword>Ventral intermediate Thalamus (VIM)</keyword>
  <keyword>Local field potentials (LFPs)</keyword>
  <keyword>Closed loop therapy</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/NCT02264925
org study id: CHUBX 2013/15
nct id: NCT02264925
lead sponsor: 
collaborator: 
has dmc: No
The objective of this study is to characterize through spectral analysis intra-thalamic local
      field potentials (LFPs) recorded through implanted DBS leads during periods with and without
      tremor in patients suffering from severe essential tremor.
Essential tremor (ET) is one of the most common adult movement disorders with a prevalence of
      4% in the general population. Although several medications (primidone, beta-adrenergic
      blockers, benzodiazepines…) are commonly used, few of them are truly effective for
      controlling the severe forms of ET. Since 1987, an alternative has emerged with the
      development of high frequency deep brain stimulation (DBS) of the thalamic nucleus ventralis
      intermedius (VIM). This surgical technique now represents the gold standard treatment for
      tremor-disabled ET patients. Although VIM-DBS is clearly effective for treatment of essential
      tremor (ET) a partial loss of DBS effectiveness may occur over time in some patients. This
      loss of DBS effectiveness could be related to an adaptation of the local neuronal network to
      chronic stimulation (changes in synaptic plasticity). In order to avoid this problem,
      investigators plan to develop a intermittent mode of VIM stimulation using a new Medtronic
      device combining a DBS system with local field potential (LFPs) sensing capability. First,
      investigators propose to analyse VIM LFPs in order to define a tremor biomarker in 10
      patients operated for severe ET. Thereafter, investigators will automatically detect this
      biomarker using a specific algorithm and use it to trigger stimulation at the onset of tremor
      only. Thus, this project will allow us to optimize DBS therapy in ET, by improving the
      longevity of implantable devices and avoiding the loss of efficacy previously reported
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: LFPs records 3 month after implantation
time frame: 3 month after implantation
description: in order to characterize the features of tremor-related thalamic activity during the initiation of movement-related tremor-induced activity
measure: LFPs records 12 month after implantation
time frame: 12 month after implantation
description: in order to characterize the features of tremor-related thalamic activity during the initiation of movement-related tremor-induced activity
arm group label: Deep Brain Stimulation
arm group type: Experimental
description: All of included patients will receive a standard deep brain stimulation of the thalamus in order to reduce their essential tremor
intervention type: Device
intervention name: Deep Brain Stimulation with Medtronic Activa PC+S systems
description: Deep Brain Stimulation of VIM.
arm group label: Deep Brain Stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: BURBAUD Pierre, MD-PhD
role: Study Director
affiliation: University Hospital Bordeaux, France
last name: Nicolas LANGBOUR, PhD
role: Study Chair
affiliation: IMN CNRS UMR 5293, Université Bordeaux 2 Segalen
facility: 
country: France
citation: Barbe MT, Liebhart L, Runge M, Pauls KA, Wojtecki L, Schnitzler A, Allert N, Fink GR, Sturm V, Maarouf M, Timmermann L. Deep brain stimulation in the nucleus ventralis intermedius in patients with essential tremor: habituation of tremor suppression. J Neurol. 2011 Mar;258(3):434-9. doi: 10.1007/s00415-010-5773-3. Epub 2010 Oct 8.
PMID: 20927533
citation: Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J. Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol. 1987;50(1-6):344-6. doi: 10.1159/000100803.
PMID: 3329873
citation: Blomstedt P, Hariz GM, Hariz MI, Koskinen LO. Thalamic deep brain stimulation in the treatment of essential tremor: a long-term follow-up. Br J Neurosurg. 2007 Oct;21(5):504-9. doi: 10.1080/02688690701552278.
PMID: 17922323
citation: Brown P, Williams D. Basal ganglia local field potential activity: character and functional significance in the human. Clin Neurophysiol. 2005 Nov;116(11):2510-9. doi: 10.1016/j.clinph.2005.05.009. Epub 2005 Jul 18.
PMID: 16029963
citation: Garcia Ruiz P, Muniz de Igneson J, Lopez Ferro O, Martin C, Magarinos Ascone C. Deep brain stimulation holidays in essential tremor. J Neurol. 2001 Aug;248(8):725-6. doi: 10.1007/s004150170127. No abstract available.
PMID: 11569910
citation: Hariz MI, Shamsgovara P, Johansson F, Hariz G, Fodstad H. Tolerance and tremor rebound following long-term chronic thalamic stimulation for Parkinsonian and essential tremor. Stereotact Funct Neurosurg. 1999;72(2-4):208-18. doi: 10.1159/000029728.
PMID: 10853080
citation: Limousin P, Speelman JD, Gielen F, Janssens M. Multicentre European study of thalamic stimulation in parkinsonian and essential tremor. J Neurol Neurosurg Psychiatry. 1999 Mar;66(3):289-96. doi: 10.1136/jnnp.66.3.289.
PMID: 10084526
citation: Schuurman PR, Bosch DA, Bossuyt PM, Bonsel GJ, van Someren EJ, de Bie RM, Merkus MP, Speelman JD. A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor. N Engl J Med. 2000 Feb 17;342(7):461-8. doi: 10.1056/NEJM200002173420703.
PMID: 10675426
citation: Stacy MA, Elble RJ, Ondo WG, Wu SC, Hulihan J; TRS study group. Assessment of interrater and intrarater reliability of the Fahn-Tolosa-Marin Tremor Rating Scale in essential tremor. Mov Disord. 2007 Apr 30;22(6):833-8. doi: 10.1002/mds.21412.
PMID: 17343274
citation: Yoshida F, Martinez-Torres I, Pogosyan A, Holl E, Petersen E, Chen CC, Foltynie T, Limousin P, Zrinzo LU, Hariz MI, Brown P. Value of subthalamic nucleus local field potentials recordings in predicting stimulation parameters for deep brain stimulation in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2010 Aug;81(8):885-9. doi: 10.1136/jnnp.2009.190918. Epub 2010 May 12.
PMID: 20466699
responsible party type: Sponsor
mesh term: Tremor
mesh term: Essential Tremor