<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/NCT03027310</url>
  </required_header>
  <id_info>
    <org_study_id>170035</org_study_id>
    <secondary_id>17-N-0035</secondary_id>
    <nct_id>NCT03027310</nct_id>
  </id_info>
  <brief_title>Clinical and Physiological Studies of Tremor Syndromes</brief_title>
  <official_title>Clinical and Physiological Studies of Tremor Syndromes</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>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Researchers have some data on how the brain controls movement and why some people have&#xD;
      tremor. But the causes of tremor are not fully known. Researchers want to study people with&#xD;
      tremor to learn about changes in the brain and possible causes of tremor.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To better understand how the brain controls movement, learn more about tremor, and train&#xD;
      movement disorder specialists.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      People ages 18 and older with a diagnosed tremor syndrome&#xD;
&#xD;
      Healthy volunteers ages 18 and older&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be screened with:&#xD;
&#xD;
        -  Medical history&#xD;
&#xD;
        -  Physical exam&#xD;
&#xD;
        -  Urine tests&#xD;
&#xD;
        -  Clinical rating scales&#xD;
&#xD;
        -  Health questions&#xD;
&#xD;
        -  They may have electromyography (EMG) or accelerometry. Sensors or electrodes taped to&#xD;
           the skin measure movement.&#xD;
&#xD;
      Participation lasts up to 1 year.&#xD;
&#xD;
      Some participants will have a visit to examine their tremor more. They may have rating&#xD;
      scales, EMG, and drawing and writing tests.&#xD;
&#xD;
      Participants will be in 1 or more substudies. These will require up to 7 visits. Visits could&#xD;
      include the following:&#xD;
&#xD;
        -  EMG with accelerometry&#xD;
&#xD;
        -  Small electrodes taped on the body give small electric shocks that stimulate nerves.&#xD;
&#xD;
        -  MRI: Participants lie on a table that slides into a cylinder that takes pictures of the&#xD;
           body while they do simple tasks.&#xD;
&#xD;
        -  Small electrodes on the scalp record brain waves.&#xD;
&#xD;
        -  A cone with detectors on the head measures brain activity while participants do tasks.&#xD;
&#xD;
        -  A wire coil held on the scalp gives an electrical current that affects brain activity.&#xD;
&#xD;
        -  Tests for thinking, memory, smell, hearing, or vision&#xD;
&#xD;
        -  Electrodes on the head give a weak electrical current that affects brain activity.&#xD;
&#xD;
        -  Photographs or videos of movement&#xD;
&#xD;
      Participant data may be shared with other researchers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives&#xD;
&#xD;
      The purpose of this protocol is to study the phenotypic spectrum and the pathophysiology of&#xD;
      tremor syndromes by performing small behavioral, electrophysiological and neuroimaging&#xD;
      sub-studies. The protocol includes techniques with minimal risk (standard clinical&#xD;
      evaluation, MRI, EEG, peripheral nerve stimulation, single and paired pulse TMS) and certain&#xD;
      sub-studies may involve healthy volunteers. This protocol aims to study neurophysiological&#xD;
      and behavioral outcomes in defined groups of patients with tremor syndromes, to inform future&#xD;
      hypothesis-driven and confirmatory studies, which will be developed and submitted as separate&#xD;
      protocols. For this purpose, we aim to conduct 1) pilot sub-studies, 2) individual patient&#xD;
      investigations, 3) technical development studies.&#xD;
&#xD;
      Study population&#xD;
&#xD;
      We intend to enroll up to 300 patients with essential tremor and other isolated action tremor&#xD;
      syndromes, as well as 150 healthy volunteers.&#xD;
&#xD;
      Design&#xD;
&#xD;
      This is a non-hypothesis driven study involving standardized phenotyping After patients and&#xD;
      healthy volunteers complete a screening visit, patients will undergo a standardized&#xD;
      phenotyping visit including clinical rating scales as well as electrophysiological&#xD;
      tremorworkup. Patient and healthy controls may then be enrolled in sub-studies, and if a&#xD;
      substudy leads to results of interest, a separate protocol will be submitted with a priori&#xD;
      hypotheses, specific study design and power analysis adapted from the pilot or exploratory&#xD;
      sub-studies performed in the present protocol.&#xD;
&#xD;
      Outcome measures&#xD;
&#xD;
      Outcome measures applied in this protocol involve methods for tremor phenotyping such as&#xD;
      clinical rating scales and questionnaires, electrophysiological tremor studies, videotaped&#xD;
      exam, as well as digitizing based tasks. During the sub-studies focused on the&#xD;
      neurophysiological characterization of tremor syndromes, the following outcome measures will&#xD;
      be applied: EMG: we will analyze tremor signals using spectral analyses, coherence analyses,&#xD;
      and in combination with accelerometry, EEG, MEG, and TMS to explore tremor-networks. MRI: we&#xD;
      will analyze measures such as the amplitude of the BOLD signal (fMRI); tractography between&#xD;
      seed and target regions of interest (using DTI); morphometry of brain regions (using VBM);&#xD;
      and different neurotransmitter levels in brain regions of interest (using MRS). EEG and MEG:&#xD;
      we will quantify measures such as corticomuscular coherence, event- or task-related&#xD;
      potentials, synchronization/desynchronization, and coherence between sensors or sources&#xD;
      located close to the brain areas of interest. TMS: we will analyze measures such as MEP&#xD;
      amplitude and central conduction time, as well as measures of cortical excitability and&#xD;
      inhibition paradigms. Behavioral measures: we will quantify measures of voluntary movement&#xD;
      involving tremor, reaction times to initiate movements, EMG patterns, movement kinematics&#xD;
      (position, velocity, acceleration, curvature), eye movement. Actigraphy: We will quantify&#xD;
      continuous recordings of motion sensors involving multiaxial accelerometers and gyroscopes.&#xD;
      Furthermore, we may measure autonomic data during the course of experiments (such as blood&#xD;
      pressure, skin co ductance, and respiratory rate) which would correlate to the outcome&#xD;
      measures.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 5, 2017</start_date>
  <completion_date type="Actual">March 23, 2022</completion_date>
  <primary_completion_date type="Actual">March 23, 2022</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>methods for tremor phenotyping</measure>
    <time_frame>throughout protocol</time_frame>
    <description>clinical rating scales and questionnaires, electrophysiological tremor studies, videotaped exam, as well as digitizing based tasks. EMG, EEG, MEG, TMS, MRI. Behavioral measures such as reaction times to initiate movements, EMG patterns, movement kinematics, eye movement.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">85</enrollment>
  <condition>Parkinson Disease</condition>
  <condition>Dystonia</condition>
  <condition>Essential Tremor</condition>
  <arm_group>
    <arm_group_label>Healthy Volunteers</arm_group_label>
    <description>adult healthy volunteers</description>
  </arm_group>
  <arm_group>
    <arm_group_label>tremor patients</arm_group_label>
    <description>adult patients with tremor</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Experimental subjects will include healthy volunteer subjects and patients with tremor&#xD;
        syndromes including, but not limited to ET, PD-tremor, and dystonic tremor. The diagnosis&#xD;
        will be made by a movement disorders neurologist at the NINDS movement disorders clinics.&#xD;
        Healthy volunteers will be recruited for the following purposes: (1) to optimize data&#xD;
        acquisition and analysis techniques; and (2) to serve as negative controls for clinical,&#xD;
        imaging, and biological variables measured in the patient cohorts. Without data obtained&#xD;
        from healthy volunteers, there is no way to determine whether subtle findings in tremor&#xD;
        (e.g., physiological tremor) are truly abnormal. The inclusion of healthy volunteers&#xD;
        therefore allows to correctly threshold and quantify observed abnormalities. Healthy&#xD;
        volunteers may also include non-affected family members of patients with tremor&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA FOR TREMOR PATIENTS:&#xD;
&#xD;
          -  Patients diagnosed with a tremor syndrome, including, but not limited to&#xD;
&#xD;
               -  Essential tremor (per definition of the Tremor Research Group)&#xD;
&#xD;
               -  Parkinson disease (per UK Brain Bank criteria)&#xD;
&#xD;
               -  Focal tremor such as isolated head tremor, voice tremor&#xD;
&#xD;
               -  Task-specific tremor such as primary writing tremor&#xD;
&#xD;
               -  Orthostatic tremor&#xD;
&#xD;
               -  Patients with other tremor syndromes such as dystonic tremor, intention tremor,&#xD;
                  etc.&#xD;
&#xD;
          -  Age 18 or older&#xD;
&#xD;
          -  Able to give informed consent&#xD;
&#xD;
          -  Agree to not drink caffeine or alcohol for 12 hours before phenotyping and selected&#xD;
             sub-study visits because both agents can modify brain activity and may confound&#xD;
             outcome measures.&#xD;
&#xD;
        INCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:&#xD;
&#xD;
          -  Age 18 or older.&#xD;
&#xD;
          -  Able to give informed consent.&#xD;
&#xD;
          -  Agree to not consume caffeine or alcohol for 12 hours before selected sub-study visits&#xD;
             because both agents may modify the activity of the brain during the study.&#xD;
&#xD;
        EXCLUSION CRITERIA FOR TREMOR PATIENTS:&#xD;
&#xD;
          -  Problematic alcohol use, as defined by a score of 8 or higher on the WHO Alcohol Use&#xD;
             Disorders Identification Test (AUDIT).&#xD;
&#xD;
          -  History of a brain tumor, a stroke, traumatic brain injury, epilepsy or a history of&#xD;
             seizures.&#xD;
&#xD;
          -  History of psychotic disorder, Bipolar Disorder or a current depressive episode.&#xD;
&#xD;
          -  History or clinical evidence of another neurologic disorder than a tremor syndrome as&#xD;
             defined above, which may interfere with the ability to comply with protocol&#xD;
             requirements or interpret the obtained results.&#xD;
&#xD;
        EXCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:&#xD;
&#xD;
          -  Have abnormal findings of clinical significance on the neurological examination that&#xD;
             may affect the scientific integrity of the study&#xD;
&#xD;
          -  Problematic alcohol use, as defined by a score of 8 or higher on the WHO Alcohol Use&#xD;
             Disorders Identification Test (AUDIT)&#xD;
&#xD;
          -  History of a brain tumor, a stroke, traumatic brain injury, epilepsy or a history of&#xD;
             seizures.&#xD;
&#xD;
          -  History of psychotic disorder, Bipolar Disorder or a current depressive episode.&#xD;
&#xD;
        ADDITIONAL EXCLUSION CRITERIA FOR MOVEMENT DISORDER PATIENTS AND HEALTHY VOLUNTEERS&#xD;
        SPECIFICALLY FOR MRI:&#xD;
&#xD;
        We will follow the NMR Center guidelines for MR safety.&#xD;
&#xD;
        Some of the exclusions are:&#xD;
&#xD;
          -  Have non-MRI compatible metal in the body, such as a cardiac pacemaker, brain&#xD;
             stimulator, shrapnel, surgical metal, clips in the brain or on blood vessels, cochlear&#xD;
             implants, artificial heart valves or ferromagnetic fragments in the eye or oral cavity&#xD;
             as these make having an MRI unsafe.&#xD;
&#xD;
          -  Unable to lie flat on the back for the expected length of the experiment.&#xD;
&#xD;
          -  Have uncontrolled movements of the head.&#xD;
&#xD;
          -  Have an abnormality on the brain imaging or neurologic examination not related to the&#xD;
             diagnosis.&#xD;
&#xD;
          -  Uncomfortable being in a small space for the expected length of the experiment.&#xD;
&#xD;
          -  Non-removable body piercing or tattoo posing MRI risk&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
        ADDITIONAL EXCLUSION CRITERIA FOR TREMOR PATIENTS AND HEALTHY VOLUNTEERS FOR TMS AND MRI:&#xD;
&#xD;
          -  Ferromagnetic metal in the cranial cavity or eye, e.g. aneurysm clip or ocular foreign&#xD;
             body.&#xD;
&#xD;
          -  Implanted electronic device including deep brain stimulation systems.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Debra J Ehrlich, 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>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-N-0035.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>August 24, 2023</verification_date>
  <study_first_submitted>January 18, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <last_update_submitted>August 25, 2023</last_update_submitted>
  <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dystonic Tremor</keyword>
  <keyword>Essential Tremor</keyword>
  <keyword>Parkinsonism</keyword>
  <keyword>Voice Tremor</keyword>
  <keyword>Parkinson's Disease</keyword>
  <keyword>Natural History</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>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>.We will share all collected deidentified IPD at the request of others after publication. Data will not be sent until the applicable approvals and data sharing agreement has been obtained.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>Starting 6 months after publication.</ipd_time_frame>
    <ipd_access_criteria>Requests will be considered on a case-by-case basis and we will try to uphold the NIH data-sharing directive. At the same time we may need IRB approval and/or data sharing agreements to be in place before we send data to others.</ipd_access_criteria>
  </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/NCT03027310
org study id: 170035
secondary id: 17-N-0035
nct id: NCT03027310
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Background:

      Researchers have some data on how the brain controls movement and why some people have
      tremor. But the causes of tremor are not fully known. Researchers want to study people with
      tremor to learn about changes in the brain and possible causes of tremor.

      Objective:

      To better understand how the brain controls movement, learn more about tremor, and train
      movement disorder specialists.

      Eligibility:

      People ages 18 and older with a diagnosed tremor syndrome

      Healthy volunteers ages 18 and older

      Design:

      Participants will be screened with:

        -  Medical history

        -  Physical exam

        -  Urine tests

        -  Clinical rating scales

        -  Health questions

        -  They may have electromyography (EMG) or accelerometry. Sensors or electrodes taped to
           the skin measure movement.

      Participation lasts up to 1 year.

      Some participants will have a visit to examine their tremor more. They may have rating
      scales, EMG, and drawing and writing tests.

      Participants will be in 1 or more substudies. These will require up to 7 visits. Visits could
      include the following:

        -  EMG with accelerometry

        -  Small electrodes taped on the body give small electric shocks that stimulate nerves.

        -  MRI: Participants lie on a table that slides into a cylinder that takes pictures of the
           body while they do simple tasks.

        -  Small electrodes on the scalp record brain waves.

        -  A cone with detectors on the head measures brain activity while participants do tasks.

        -  A wire coil held on the scalp gives an electrical current that affects brain activity.

        -  Tests for thinking, memory, smell, hearing, or vision

        -  Electrodes on the head give a weak electrical current that affects brain activity.

        -  Photographs or videos of movement

      Participant data may be shared with other researchers.
Objectives

      The purpose of this protocol is to study the phenotypic spectrum and the pathophysiology of
      tremor syndromes by performing small behavioral, electrophysiological and neuroimaging
      sub-studies. The protocol includes techniques with minimal risk (standard clinical
      evaluation, MRI, EEG, peripheral nerve stimulation, single and paired pulse TMS) and certain
      sub-studies may involve healthy volunteers. This protocol aims to study neurophysiological
      and behavioral outcomes in defined groups of patients with tremor syndromes, to inform future
      hypothesis-driven and confirmatory studies, which will be developed and submitted as separate
      protocols. For this purpose, we aim to conduct 1) pilot sub-studies, 2) individual patient
      investigations, 3) technical development studies.

      Study population

      We intend to enroll up to 300 patients with essential tremor and other isolated action tremor
      syndromes, as well as 150 healthy volunteers.

      Design

      This is a non-hypothesis driven study involving standardized phenotyping After patients and
      healthy volunteers complete a screening visit, patients will undergo a standardized
      phenotyping visit including clinical rating scales as well as electrophysiological
      tremorworkup. Patient and healthy controls may then be enrolled in sub-studies, and if a
      substudy leads to results of interest, a separate protocol will be submitted with a priori
      hypotheses, specific study design and power analysis adapted from the pilot or exploratory
      sub-studies performed in the present protocol.

      Outcome measures

      Outcome measures applied in this protocol involve methods for tremor phenotyping such as
      clinical rating scales and questionnaires, electrophysiological tremor studies, videotaped
      exam, as well as digitizing based tasks. During the sub-studies focused on the
      neurophysiological characterization of tremor syndromes, the following outcome measures will
      be applied: EMG: we will analyze tremor signals using spectral analyses, coherence analyses,
      and in combination with accelerometry, EEG, MEG, and TMS to explore tremor-networks. MRI: we
      will analyze measures such as the amplitude of the BOLD signal (fMRI); tractography between
      seed and target regions of interest (using DTI); morphometry of brain regions (using VBM);
      and different neurotransmitter levels in brain regions of interest (using MRS). EEG and MEG:
      we will quantify measures such as corticomuscular coherence, event- or task-related
      potentials, synchronization/desynchronization, and coherence between sensors or sources
      located close to the brain areas of interest. TMS: we will analyze measures such as MEP
      amplitude and central conduction time, as well as measures of cortical excitability and
      inhibition paradigms. Behavioral measures: we will quantify measures of voluntary movement
      involving tremor, reaction times to initiate movements, EMG patterns, movement kinematics
      (position, velocity, acceleration, curvature), eye movement. Actigraphy: We will quantify
      continuous recordings of motion sensors involving multiaxial accelerometers and gyroscopes.
      Furthermore, we may measure autonomic data during the course of experiments (such as blood
      pressure, skin co ductance, and respiratory rate) which would correlate to the outcome
      measures.
observational model: Case-Control
time perspective: Prospective
measure: methods for tremor phenotyping
time frame: throughout protocol
description: clinical rating scales and questionnaires, electrophysiological tremor studies, videotaped exam, as well as digitizing based tasks. EMG, EEG, MEG, TMS, MRI. Behavioral measures such as reaction times to initiate movements, EMG patterns, movement kinematics, eye movement.
arm group label: Healthy Volunteers
description: adult healthy volunteers
arm group label: tremor patients
description: adult patients with tremor
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Debra J Ehrlich, M.D.
role: Principal Investigator
affiliation: National Institute of Neurological Disorders and Stroke (NINDS)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-N-0035.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Dystonia
mesh term: Tremor
mesh term: Essential Tremor
sharing ipd: Yes
ipd description: .We will share all collected deidentified IPD at the request of others after publication. Data will not be sent until the applicable approvals and data sharing agreement has been obtained.
ipd info type: Study Protocol
ipd time frame: Starting 6 months after publication.
ipd access criteria: Requests will be considered on a case-by-case basis and we will try to uphold the NIH data-sharing directive. At the same time we may need IRB approval and/or data sharing agreements to be in place before we send data to others.