<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/NCT03041714</url>
  </required_header>
  <id_info>
    <org_study_id>170053</org_study_id>
    <secondary_id>17-N-0053</secondary_id>
    <nct_id>NCT03041714</nct_id>
  </id_info>
  <brief_title>Neurophysiologic Study of Patient With Essential Tremor and Dystonic Tremor</brief_title>
  <official_title>Neurophysiologic Study of Patients With Essential Tremor and Dystonic Tremor</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Neurological Disorders and Stroke (NINDS)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Essential tremor is when a person has tremor, but no other neurological symptoms. Dystonic&#xD;
      tremor is when a person also has dystonia. Dystonia is a condition in which muscle&#xD;
      contraction causes changes in posture. Researchers do not fully know what areas of the brain&#xD;
      cause these tremors, or how the types differ. They also do not know what tests can identify&#xD;
      the differences.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To look at differences between essential tremor and dystonic tremor.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      People ages 18 and older with or without tremor&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be screened with medical history, physical exam, and urine tests. Those&#xD;
      with tremor will complete questionnaires about how tremor affects them.&#xD;
&#xD;
      The screening and study visits can be done on the same day or on separate days.&#xD;
&#xD;
      Participants will have 1 or 2 study visits. These include magnetic resonance imaging (MRI)&#xD;
      and tremor testing.&#xD;
&#xD;
      For MRI, participants will lie on a table that slides in and out of a cylinder that takes&#xD;
      pictures. Sensors on the skin measure breathing, heart rate, and muscle activity. This takes&#xD;
      about 2 hours.&#xD;
&#xD;
      Tremor testing will include transcranial magnetic stimulation (TMS), electrical stimulation&#xD;
      of the fingers, doing a movement task, and recording of tremor movements. For TMS, two wire&#xD;
      coils will be held on the scalp and a brief magnetic field will be produced. A brief&#xD;
      electrical current will pass through the coils. For the other tests, small sticky pad&#xD;
      electrodes will be put on the skin. Participants will move their hand when they hear a sound.&#xD;
      They will get weak electrical shocks to their fingers. These tests will take 3-4 hours.&#xD;
&#xD;
      Participants can take part in either or both parts of the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives:&#xD;
&#xD;
      To explore a neurophysiological difference between patients with essential tremor (ET) and&#xD;
      dystonic tremor (DT).&#xD;
&#xD;
      Sample Size and Population:&#xD;
&#xD;
      We plan to recruit 26 healthy volunteers (HVs), 26 patients with ET, 26 patients with&#xD;
      dystonic tremor from the Movement Disorders and Botulinum Toxin (BoNT) clinics of HMCS. The&#xD;
      dystonic tremor group will be divided into 2 subgroups: pure dystonic tremor (pDT), patients&#xD;
      who have dystonia and tremor in the same limb, tremor associated with dystonia (TAWD),&#xD;
      patients who have isolated tremor with dystonia elsewhere. We plan to enroll 13 patients with&#xD;
      pDT and 13 with TAWD. We plan to recruit a total of 20 participants including patients with&#xD;
      ET, DT and HVs if the use of data from protocol 10-N-0009 is permitted. All neurophysiologic&#xD;
      results will be compared between patients and HVs.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Subjects will come to NIH for at least one study visit. All subjects will undergo a screening&#xD;
      visit including taking a medical history and physical examination. Then the patients will be&#xD;
      scored clinically for tremor in both ET and DT and dystonia only for DT. All subjects will&#xD;
      have a series of transcranial magnetic stimulation (TMS) studies. TMS-induced&#xD;
      electromyographic (EMG) activity of hand and forearm muscles will be recorded as motor evoked&#xD;
      potentials (MEPs). Pyramidal threshold will be determined by inion stimulation. Then,&#xD;
      paired-pulse stimulation at the cerebellum followed by the motor cortex will be performed at&#xD;
      rest and at tonic activation of the hand muscle. Only patients will have recordings of tremor&#xD;
      at rest, postural holding, and with action and specific tasks such as writing by using&#xD;
      accelerometry and EMG. Additionally, a single TMS will be delivered to the motor cortex or&#xD;
      cerebellum while the patients elicit their tremor in order to explore the effect of TMS on&#xD;
      tremor. All subjects (both HVs and ET, DT) will be tested for their threshold to discriminate&#xD;
      somatosensory stimulation and for their performance of quick ballistic movements. All&#xD;
      subjects will also undergo a magnetic resonance imaging (MRI) study which includes structural&#xD;
      MRI, resting state functional MRI (rsfMRI), diffusion tensor imaging (DTI), MR spectroscopy.&#xD;
      The subjects can either undergo the MRI study on the same visit as the other parts of&#xD;
      experiment or do it separately.&#xD;
&#xD;
      Outcome measurements:&#xD;
&#xD;
      The various neurophysiological results include the data from the TMS experiment, tremor&#xD;
      analysis, threshold of temporal discrimination, ballistic movement and MRI experiment. These&#xD;
      results will be compared between HVs and patients group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 7, 2017</start_date>
  <completion_date type="Actual">March 22, 2018</completion_date>
  <primary_completion_date type="Actual">March 22, 2018</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>The various neurophysiological results including the data from TMS experiment, tremor analysis, threshold of temporal discrimination, ballistic movement and MRI experiment. These results will be compared between HVs and patients group.</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">2</enrollment>
  <condition>Essential Tremor</condition>
  <condition>Cervical Dystonia</condition>
  <condition>Focal Dystonia</condition>
  <arm_group>
    <arm_group_label>Normal volunteers</arm_group_label>
    <description>people who are healthy and without tremor</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Essential tremor</arm_group_label>
    <description>Patients with essential tremor</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dystonic tremor</arm_group_label>
    <description>patient with tremor who also have dystonia</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients will be referred to NIH or may refer themselves from all over the United States.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA&#xD;
&#xD;
        Tremor Subjects:&#xD;
&#xD;
          -  Must be 18 years or older&#xD;
&#xD;
          -  Fulfill the diagnostic criteria of essential tremor, pure dystonic tremor and tremor&#xD;
             associated dystonia, as defined by the Consensus Statement of the Movement Disorder&#xD;
             Society on Tremor, 1998. We will recruit patients displaying hand tremors in each&#xD;
             group as the follows:&#xD;
&#xD;
               -  Hand tremor patients in ET group.&#xD;
&#xD;
               -  Dystonic hand tremor patients in pDT group.&#xD;
&#xD;
               -  Cervical dystonia (CD) patients or spasmodic dysphonia and hand tremor without&#xD;
                  clinical evidence of hand dystonia in TAWD group.&#xD;
&#xD;
          -  Ability to give informed consent.&#xD;
&#xD;
          -  Ability to comply with all study procedures, based on the judgment by the&#xD;
             investigator(s).&#xD;
&#xD;
          -  Agree to not drink caffeine or alcohol for 48 hours before participating in the&#xD;
             protocol.&#xD;
&#xD;
        Healthy Volunteers:&#xD;
&#xD;
          -  Must be 18 years or older&#xD;
&#xD;
          -  Absence of dystonia or other neurological disorder with any effect on the motor or&#xD;
             sensory systems.&#xD;
&#xD;
          -  Ability to give informed consent.&#xD;
&#xD;
          -  Ability to comply with all study procedures, based on the judgment by the&#xD;
             investigator(s).&#xD;
&#xD;
          -  Agree to not drink caffeine or alcohol for 48 hours before participating in the&#xD;
             protocol.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        Patients:&#xD;
&#xD;
          -  Botulinum toxin treatment &lt; 3 months prior to visit.&#xD;
&#xD;
          -  Employees and/or staff of NINDS&#xD;
&#xD;
          -  Has used illegal drugs within the past 6 months based on history. The intent is to&#xD;
             exclude those with drug use that may affect study results. Participants who appear to&#xD;
             be intoxicated at the time of testing will be rescheduled.&#xD;
&#xD;
          -  Has more than 7 alcoholic drinks a week in the case of a woman and 14 alcoholic drinks&#xD;
             a week in the case of a man.&#xD;
&#xD;
          -  Abnormal findings on neurologic exam (other than tremor and dystonia in patient group)&#xD;
&#xD;
          -  Has had a brain tumor, a stroke, head trauma, epilepsy or a history of seizures.&#xD;
&#xD;
          -  Has major depression or any major mental disorders (axis I disorders)&#xD;
&#xD;
          -  Has a neurologic disorder other than tremor or dystonia&#xD;
&#xD;
          -  Has had a head injury where there was a loss of consciousness for more than a few&#xD;
             seconds.&#xD;
&#xD;
          -  Currently taking primidone, anticholinergics or benzodiazepines.&#xD;
&#xD;
        Healthy Volunteers:&#xD;
&#xD;
          -  Employees and/or staff of NINDS&#xD;
&#xD;
          -  Has used illegal drugs within the past 6 months based on history. The intent is to&#xD;
             exclude those with drug use that may affect study results. Participants who appear to&#xD;
             be intoxicated at the time of testing will be rescheduled.&#xD;
&#xD;
          -  Has more than 7 alcoholic drinks a week in the case of a woman and 14 alcoholic drinks&#xD;
             a week in the case of a man.&#xD;
&#xD;
          -  Abnormal findings on neurologic exam.&#xD;
&#xD;
          -  Has had a brain tumor, a stroke, head trauma, epilepsy or a history of seizures.&#xD;
&#xD;
          -  Has a neurologic disorder other than tremor or dystonia&#xD;
&#xD;
          -  Has major depression or any major mental disorders (axis I disorders)&#xD;
&#xD;
          -  Has had a head injury where there was a loss of consciousness for more than a few&#xD;
             seconds.&#xD;
&#xD;
        Additional Exclusion Criteria for MRI:&#xD;
&#xD;
          -  Has metal in the body, such as a cardiac pacemaker, brain stimulator, shrapnel,&#xD;
             surgical metal, clips in the brain, cochlear implants, or metal fragments in the eye&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Unable to lie flat on the back for the expect length of the study up to 3 hours.&#xD;
&#xD;
          -  Feeling uncomfortable being in a small space for up to 3 hours.&#xD;
&#xD;
        &lt;TAB&gt;&#xD;
&#xD;
        Additional Exclusion Criteria for TMS:&#xD;
&#xD;
          -  Has metal in the body, such as a cardiac pacemaker, brain stimulator, shrapnel,&#xD;
             surgical metal, clips in the brain, cochlear implants, or metal fragments in the eye&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark Hallett, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Neurological Disorders and Stroke (NINDS)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord. 1998;13 Suppl 3:2-23. doi: 10.1002/mds.870131303.</citation>
    <PMID>9827589</PMID>
  </reference>
  <reference>
    <citation>Ni Z, Pinto AD, Lang AE, Chen R. Involvement of the cerebellothalamocortical pathway in Parkinson disease. Ann Neurol. 2010 Dec;68(6):816-24. doi: 10.1002/ana.22221.</citation>
    <PMID>21194152</PMID>
  </reference>
  <reference>
    <citation>Pascual-Leone A, Valls-Sole J, Toro C, Wassermann EM, Hallett M. Resetting of essential tremor and postural tremor in Parkinson's disease with transcranial magnetic stimulation. Muscle Nerve. 1994 Jul;17(7):800-7. doi: 10.1002/mus.880170716.</citation>
    <PMID>8008009</PMID>
  </reference>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>February 2, 2017</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>July 31, 2018</last_update_submitted>
  <last_update_submitted_qc>July 31, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Essential Tremor</keyword>
  <keyword>Cervical Dystonia</keyword>
  <keyword>Hand Dystonia</keyword>
  <keyword>Neurophysiology</keyword>
  <keyword>Dystonic Tremor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dystonia</mesh_term>
    <mesh_term>Dystonic Disorders</mesh_term>
    <mesh_term>Tremor</mesh_term>
    <mesh_term>Essential Tremor</mesh_term>
    <mesh_term>Torticollis</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/NCT03041714
org study id: 170053
secondary id: 17-N-0053
nct id: NCT03041714
lead sponsor: 
Background:

      Essential tremor is when a person has tremor, but no other neurological symptoms. Dystonic
      tremor is when a person also has dystonia. Dystonia is a condition in which muscle
      contraction causes changes in posture. Researchers do not fully know what areas of the brain
      cause these tremors, or how the types differ. They also do not know what tests can identify
      the differences.

      Objective:

      To look at differences between essential tremor and dystonic tremor.

      Eligibility:

      People ages 18 and older with or without tremor

      Design:

      Participants will be screened with medical history, physical exam, and urine tests. Those
      with tremor will complete questionnaires about how tremor affects them.

      The screening and study visits can be done on the same day or on separate days.

      Participants will have 1 or 2 study visits. These include magnetic resonance imaging (MRI)
      and tremor testing.

      For MRI, participants will lie on a table that slides in and out of a cylinder that takes
      pictures. Sensors on the skin measure breathing, heart rate, and muscle activity. This takes
      about 2 hours.

      Tremor testing will include transcranial magnetic stimulation (TMS), electrical stimulation
      of the fingers, doing a movement task, and recording of tremor movements. For TMS, two wire
      coils will be held on the scalp and a brief magnetic field will be produced. A brief
      electrical current will pass through the coils. For the other tests, small sticky pad
      electrodes will be put on the skin. Participants will move their hand when they hear a sound.
      They will get weak electrical shocks to their fingers. These tests will take 3-4 hours.

      Participants can take part in either or both parts of the study.
Objectives:

      To explore a neurophysiological difference between patients with essential tremor (ET) and
      dystonic tremor (DT).

      Sample Size and Population:

      We plan to recruit 26 healthy volunteers (HVs), 26 patients with ET, 26 patients with
      dystonic tremor from the Movement Disorders and Botulinum Toxin (BoNT) clinics of HMCS. The
      dystonic tremor group will be divided into 2 subgroups: pure dystonic tremor (pDT), patients
      who have dystonia and tremor in the same limb, tremor associated with dystonia (TAWD),
      patients who have isolated tremor with dystonia elsewhere. We plan to enroll 13 patients with
      pDT and 13 with TAWD. We plan to recruit a total of 20 participants including patients with
      ET, DT and HVs if the use of data from protocol 10-N-0009 is permitted. All neurophysiologic
      results will be compared between patients and HVs.

      Design:

      Subjects will come to NIH for at least one study visit. All subjects will undergo a screening
      visit including taking a medical history and physical examination. Then the patients will be
      scored clinically for tremor in both ET and DT and dystonia only for DT. All subjects will
      have a series of transcranial magnetic stimulation (TMS) studies. TMS-induced
      electromyographic (EMG) activity of hand and forearm muscles will be recorded as motor evoked
      potentials (MEPs). Pyramidal threshold will be determined by inion stimulation. Then,
      paired-pulse stimulation at the cerebellum followed by the motor cortex will be performed at
      rest and at tonic activation of the hand muscle. Only patients will have recordings of tremor
      at rest, postural holding, and with action and specific tasks such as writing by using
      accelerometry and EMG. Additionally, a single TMS will be delivered to the motor cortex or
      cerebellum while the patients elicit their tremor in order to explore the effect of TMS on
      tremor. All subjects (both HVs and ET, DT) will be tested for their threshold to discriminate
      somatosensory stimulation and for their performance of quick ballistic movements. All
      subjects will also undergo a magnetic resonance imaging (MRI) study which includes structural
      MRI, resting state functional MRI (rsfMRI), diffusion tensor imaging (DTI), MR spectroscopy.
      The subjects can either undergo the MRI study on the same visit as the other parts of
      experiment or do it separately.

      Outcome measurements:

      The various neurophysiological results include the data from the TMS experiment, tremor
      analysis, threshold of temporal discrimination, ballistic movement and MRI experiment. These
      results will be compared between HVs and patients group.
observational model: Case-Control
time perspective: Cross-Sectional
measure: The various neurophysiological results including the data from TMS experiment, tremor analysis, threshold of temporal discrimination, ballistic movement and MRI experiment. These results will be compared between HVs and patients group.
time frame: 2 years
arm group label: Normal volunteers
description: people who are healthy and without tremor
arm group label: Essential tremor
description: Patients with essential tremor
arm group label: Dystonic tremor
description: patient with tremor who also have dystonia
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mark Hallett, M.D.
role: Principal Investigator
affiliation: National Institute of Neurological Disorders and Stroke (NINDS)
facility: 
country: United States
citation: Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord. 1998;13 Suppl 3:2-23. doi: 10.1002/mds.870131303.
PMID: 9827589
citation: Ni Z, Pinto AD, Lang AE, Chen R. Involvement of the cerebellothalamocortical pathway in Parkinson disease. Ann Neurol. 2010 Dec;68(6):816-24. doi: 10.1002/ana.22221.
PMID: 21194152
citation: Pascual-Leone A, Valls-Sole J, Toro C, Wassermann EM, Hallett M. Resetting of essential tremor and postural tremor in Parkinson's disease with transcranial magnetic stimulation. Muscle Nerve. 1994 Jul;17(7):800-7. doi: 10.1002/mus.880170716.
PMID: 8008009
responsible party type: Sponsor
mesh term: Dystonia
mesh term: Dystonic Disorders
mesh term: Tremor
mesh term: Essential Tremor
mesh term: Torticollis