<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/NCT03769961</url>
  </required_header>
  <id_info>
    <org_study_id>18608</org_study_id>
    <nct_id>NCT03769961</nct_id>
  </id_info>
  <brief_title>Ataxia in Essential Tremor: Describing the Differences Between Disease Process and Treatment Effect</brief_title>
  <acronym>ATAX</acronym>
  <official_title>Ataxia in Essential Tremor: Describing the Differences Between Disease Process and Treatment Effect (ATAX)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Portland VA Medical Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Oregon Health and Science University</source>
  <oversight_info>
    <has_dmc>No</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>
      The proposed study aims to characterize ataxia occurring in essential tremor and essential&#xD;
      tremor with DBS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives: In recent years, there has been a growing amount of evidence tying Essential&#xD;
      Tremor (ET) to cerebellar dysfunction. This has been clinically observed, demonstrated&#xD;
      through specific gait measures of ataxia (often involving tandem gait), and confirmed through&#xD;
      Positron emission tomography (PET) imaging. Deep Brain stimulation for ET has become a widely&#xD;
      utilized therapeutic intervention for patients, and the bilateral thalamic ventralis&#xD;
      intermedius (VIM) is most commonly implanted. However, it has been noted that in some&#xD;
      patients gait ataxia significantly worsens post-op. This initially was thought to be a result&#xD;
      of disease progression, but recent studies have in fact shown that this is a DBS related&#xD;
      phenomenon.&#xD;
&#xD;
      Methods: Participants will have two visits to either the Portland VA or Oregon Health &amp;&#xD;
      Science University (OHSU). At each visit, several assessments of balance, tremor, gait and&#xD;
      balance, and DBS settings will be made. The gait and balance assessments will be performed by&#xD;
      a unblinded and a blinded rater.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low enrollment&#xD;
  </why_stopped>
  <start_date type="Actual">December 1, 2018</start_date>
  <completion_date type="Actual">September 14, 2020</completion_date>
  <primary_completion_date type="Actual">September 14, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Ataxia Differences between DBS and no DBS</measure>
    <time_frame>Visit 2 (after DBS has been turned off for 3-10 days)</time_frame>
    <description>Compare the Scale of the Assessment and Rating of Ataxia (SARA) total score between DBS and no DBS participants with essential tremor. This 8-item scale rates gait (0-8 points), stance (0-6 points), sitting (0-4 points), speech disturbance (0-6 points), finger chase (0-4 points), nose-finger test (0-4 points), fast alternating hand movements (0-4 points), and heel-shin slide (0-4 points). Motor activists of the four extremities (items 5-8) assessments are performed bilaterally, mean values to obtain a total score. Cumulative score ranges from 0 (no ataxia) to 40 (most severe ataxia).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Balance Confidence</measure>
    <time_frame>Visit 2 (after DBS has been turned off for 3-10 days)</time_frame>
    <description>The Activities-Specific Balance Confidence Scale (ABC) is a subjective measure of confidence in performing various ambulatory activities without falling or experiencing a sense of unsteadiness. The ABC scale is a 16-item self-report measure in which participants rate their balance confidence on a 0-100 scale (0 = 0 no confidence, 100 = 100 complete confidence). Overall score is calculated by adding item scores and dividing by the total number of items.</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">6</enrollment>
  <condition>Essential Tremor</condition>
  <condition>Deep Brain Stimulation</condition>
  <condition>Ataxia</condition>
  <condition>Cerebellar Diseases</condition>
  <arm_group>
    <arm_group_label>ET (DBS-, Ataxia+)</arm_group_label>
    <description>Essential Tremor without DBS with Ataxia on examination</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ET (DBS-, Ataxia-)</arm_group_label>
    <description>Essential Tremor without DBS and without Ataxia on examination</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ET (DBS+, Ataxia+)</arm_group_label>
    <description>Essential Tremor with DBS with Ataxia on examination</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ET (DBS+, Ataxia-)</arm_group_label>
    <description>Essential Tremor with DBS without Ataxia</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No intervention</intervention_name>
    <description>No interventions - Observational study</description>
    <arm_group_label>ET (DBS+, Ataxia+)</arm_group_label>
    <arm_group_label>ET (DBS+, Ataxia-)</arm_group_label>
    <arm_group_label>ET (DBS-, Ataxia+)</arm_group_label>
    <arm_group_label>ET (DBS-, Ataxia-)</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Essential Tremor participants with and without ataxia&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Essential Tremor diagnosis at least 3 years duration&#xD;
&#xD;
          -  Absence of other neurological signes (such as dystonia, ataxia, or Parkinsonism)&#xD;
&#xD;
          -  Patients must be able to walk 2 minutes unassisted.&#xD;
&#xD;
          -  Patients must be able to understand and consent to be in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have had changes in DBS settings within the last 3 months.&#xD;
&#xD;
          -  Patients who have had no initial improvement or response to DBS.&#xD;
&#xD;
          -  ET medication changes in the last month.&#xD;
&#xD;
          -  Actively abusing alcohol.&#xD;
&#xD;
          -  A neurologic diagnosis other than ET that in the investigator's opinion could affect&#xD;
             gait and/or balance.&#xD;
&#xD;
          -  Atypical tremor disorder including by not limited to tremor due to multiple sclerosis,&#xD;
             medication-induced tremor, Parkinson's disease, or parkinsonian syndrome.&#xD;
&#xD;
          -  Dementia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Portland Health Care System</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Ramirez-Zamora A, Boggs H, Pilitsis JG. Reduction in DBS frequency improves balance difficulties after thalamic DBS for essential tremor. J Neurol Sci. 2016 Aug 15;367:122-7. doi: 10.1016/j.jns.2016.06.001. Epub 2016 Jun 2.</citation>
    <PMID>27423573</PMID>
  </reference>
  <results_reference>
    <citation>Nazzaro JM, Lyons KE, Pahwa R. Deep brain stimulation for essential tremor. Handb Clin Neurol. 2013;116:155-66. doi: 10.1016/B978-0-444-53497-2.00013-9.</citation>
    <PMID>24112892</PMID>
  </results_reference>
  <results_reference>
    <citation>Kronenbuerger M, Konczak J, Ziegler W, Buderath P, Frank B, Coenen VA, Kiening K, Reinacher P, Noth J, Timmann D. Balance and motor speech impairment in essential tremor. Cerebellum. 2009 Sep;8(3):389-98. doi: 10.1007/s12311-009-0111-y. Epub 2009 May 19.</citation>
    <PMID>19452239</PMID>
  </results_reference>
  <results_reference>
    <citation>Fasano A, Herzog J, Raethjen J, Rose FE, Muthuraman M, Volkmann J, Falk D, Elble R, Deuschl G. Gait ataxia in essential tremor is differentially modulated by thalamic stimulation. Brain. 2010 Dec;133(Pt 12):3635-48. doi: 10.1093/brain/awq267. Epub 2010 Oct 5.</citation>
    <PMID>20926368</PMID>
  </results_reference>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>December 6, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 10, 2018</study_first_posted>
  <last_update_submitted>September 15, 2020</last_update_submitted>
  <last_update_submitted_qc>September 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oregon Health and Science University</investigator_affiliation>
    <investigator_full_name>Amie Hiller, MD</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>essential tremor</keyword>
  <keyword>dbs</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ataxia</mesh_term>
    <mesh_term>Cerebellar Ataxia</mesh_term>
    <mesh_term>Tremor</mesh_term>
    <mesh_term>Essential Tremor</mesh_term>
    <mesh_term>Cerebellar Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Post data entry and verification, data and specimens will be de-identified (no 18 HIPAA identifiers and age aggregated for those &gt; 89 years old) and transferred to the Neurological Disorder Repository (MIRB # 3129). This repository is maintained at the Portland VA Health Care System. Verification of the coded data set creation and the absence of the identifiers will be created and retained in the study files. The research coordinator will be responsible for the creation and verification process. The key to the code will be maintained by the study and will not be released to the repository. The recipient investigator must present the data use agreement, documentation of an Institutional Review Boar (IRB) approved protocol and Informed Conset Form (ICF) allowing the release of the identifiable specimens/data, or the release of coded specimens/data.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Data will be available within 6 months of study completion.</ipd_time_frame>
    <ipd_access_criteria>Data access requests will be reviewed by an external Independent Review Board. Requestors will be required to sign a data access agreement.</ipd_access_criteria>
    <ipd_url>https://www.portland.va.gov/research/</ipd_url>
  </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/NCT03769961
org study id: 18608
nct id: NCT03769961
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The proposed study aims to characterize ataxia occurring in essential tremor and essential
      tremor with DBS.
Objectives: In recent years, there has been a growing amount of evidence tying Essential
      Tremor (ET) to cerebellar dysfunction. This has been clinically observed, demonstrated
      through specific gait measures of ataxia (often involving tandem gait), and confirmed through
      Positron emission tomography (PET) imaging. Deep Brain stimulation for ET has become a widely
      utilized therapeutic intervention for patients, and the bilateral thalamic ventralis
      intermedius (VIM) is most commonly implanted. However, it has been noted that in some
      patients gait ataxia significantly worsens post-op. This initially was thought to be a result
      of disease progression, but recent studies have in fact shown that this is a DBS related
      phenomenon.

      Methods: Participants will have two visits to either the Portland VA or Oregon Health &
      Science University (OHSU). At each visit, several assessments of balance, tremor, gait and
      balance, and DBS settings will be made. The gait and balance assessments will be performed by
      a unblinded and a blinded rater.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Ataxia Differences between DBS and no DBS
time frame: Visit 2 (after DBS has been turned off for 3-10 days)
description: Compare the Scale of the Assessment and Rating of Ataxia (SARA) total score between DBS and no DBS participants with essential tremor. This 8-item scale rates gait (0-8 points), stance (0-6 points), sitting (0-4 points), speech disturbance (0-6 points), finger chase (0-4 points), nose-finger test (0-4 points), fast alternating hand movements (0-4 points), and heel-shin slide (0-4 points). Motor activists of the four extremities (items 5-8) assessments are performed bilaterally, mean values to obtain a total score. Cumulative score ranges from 0 (no ataxia) to 40 (most severe ataxia).
measure: Balance Confidence
time frame: Visit 2 (after DBS has been turned off for 3-10 days)
description: The Activities-Specific Balance Confidence Scale (ABC) is a subjective measure of confidence in performing various ambulatory activities without falling or experiencing a sense of unsteadiness. The ABC scale is a 16-item self-report measure in which participants rate their balance confidence on a 0-100 scale (0 = 0 no confidence, 100 = 100 complete confidence). Overall score is calculated by adding item scores and dividing by the total number of items.
arm group label: ET (DBS-, Ataxia+)
description: Essential Tremor without DBS with Ataxia on examination
arm group label: ET (DBS-, Ataxia-)
description: Essential Tremor without DBS and without Ataxia on examination
arm group label: ET (DBS+, Ataxia+)
description: Essential Tremor with DBS with Ataxia on examination
arm group label: ET (DBS+, Ataxia-)
description: Essential Tremor with DBS without Ataxia
intervention type: Other
intervention name: No intervention
description: No interventions - Observational study
arm group label: ET (DBS+, Ataxia+)
arm group label: ET (DBS+, Ataxia-)
arm group label: ET (DBS-, Ataxia+)
arm group label: ET (DBS-, Ataxia-)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
facility: 
country: United States
citation: Ramirez-Zamora A, Boggs H, Pilitsis JG. Reduction in DBS frequency improves balance difficulties after thalamic DBS for essential tremor. J Neurol Sci. 2016 Aug 15;367:122-7. doi: 10.1016/j.jns.2016.06.001. Epub 2016 Jun 2.
PMID: 27423573
citation: Nazzaro JM, Lyons KE, Pahwa R. Deep brain stimulation for essential tremor. Handb Clin Neurol. 2013;116:155-66. doi: 10.1016/B978-0-444-53497-2.00013-9.
PMID: 24112892
citation: Kronenbuerger M, Konczak J, Ziegler W, Buderath P, Frank B, Coenen VA, Kiening K, Reinacher P, Noth J, Timmann D. Balance and motor speech impairment in essential tremor. Cerebellum. 2009 Sep;8(3):389-98. doi: 10.1007/s12311-009-0111-y. Epub 2009 May 19.
PMID: 19452239
citation: Fasano A, Herzog J, Raethjen J, Rose FE, Muthuraman M, Volkmann J, Falk D, Elble R, Deuschl G. Gait ataxia in essential tremor is differentially modulated by thalamic stimulation. Brain. 2010 Dec;133(Pt 12):3635-48. doi: 10.1093/brain/awq267. Epub 2010 Oct 5.
PMID: 20926368
responsible party type: Principal Investigator
investigator affiliation: Oregon Health and Science University
investigator full name: Amie Hiller, MD
investigator title: Associate Professor
mesh term: Ataxia
mesh term: Cerebellar Ataxia
mesh term: Tremor
mesh term: Essential Tremor
mesh term: Cerebellar Diseases
sharing ipd: Yes
ipd description: Post data entry and verification, data and specimens will be de-identified (no 18 HIPAA identifiers and age aggregated for those > 89 years old) and transferred to the Neurological Disorder Repository (MIRB # 3129). This repository is maintained at the Portland VA Health Care System. Verification of the coded data set creation and the absence of the identifiers will be created and retained in the study files. The research coordinator will be responsible for the creation and verification process. The key to the code will be maintained by the study and will not be released to the repository. The recipient investigator must present the data use agreement, documentation of an Institutional Review Boar (IRB) approved protocol and Informed Conset Form (ICF) allowing the release of the identifiable specimens/data, or the release of coded specimens/data.
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data will be available within 6 months of study completion.
ipd access criteria: Data access requests will be reviewed by an external Independent Review Board. Requestors will be required to sign a data access agreement.
ipd url: https://www.portland.va.gov/research/