<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/NCT03288220</url>
  </required_header>
  <id_info>
    <org_study_id>170168</org_study_id>
    <secondary_id>17-N-0168</secondary_id>
    <nct_id>NCT03288220</nct_id>
  </id_info>
  <brief_title>Influence of Brain Oscillation-Dependent TMS on Motor Function</brief_title>
  <official_title>Influence of Brain Oscillation-Dependent TMS on Motor Function</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;
      When people have a stroke, they often have difficulty moving their arms and hands.&#xD;
      Transcranial magnetic stimulation (TMS) can improve how well people with and without stroke&#xD;
      can move their arms and hands. But the effects of TMS are minor, and it doesn t work for&#xD;
      everyone. Researchers want to study how to time brain stimulation so that the effects are&#xD;
      more consistent.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To understand how the brain responds to transcranial magnetic stimulation so that treatments&#xD;
      for people with stroke can be improved.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Adults ages 18 and older who had a stroke at least 6 months ago&#xD;
&#xD;
      Healthy volunteers ages 50 and older&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will have up to 5 visits.&#xD;
&#xD;
      At visit 1, participants will be screened with medical history and physical exam.&#xD;
      Participants with stroke will also have TMS and surface electromyography (sEMG).&#xD;
&#xD;
      For TMS, a brief electrical current will pass through a wire coil on the scalp. Participants&#xD;
      may hear a click and feel a pull. Muscles may twitch. Participants may be asked to do simple&#xD;
      movements during TMS.&#xD;
&#xD;
      For sEMG, small electrodes will be attached to the skin and muscle activity will be recorded.&#xD;
&#xD;
      At visit 2, participants will have magnetic resonance imaging (MRI). They will lie on a table&#xD;
      that slides into a metal cylinder in a strong magnetic field. They will get earplugs for the&#xD;
      loud noise.&#xD;
&#xD;
      At visit 3, participants will have TMS, sEMG, and electroencephalography (EEG). For EEG,&#xD;
      small electrodes on the scalp will record brainwaves. Participants will sit still, watch a&#xD;
      movie, or do TMS.&#xD;
&#xD;
      Participants may be asked to have 2 extra visits to redo procedures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Description:&#xD;
&#xD;
      We will study if corticospinal excitability (primary outcome measure) varies across different&#xD;
      sensorimotor alpha electroencephalography (EEG) wave form oscillation phases in healthy older&#xD;
      adults and chronic stroke patients. Sensorimotor cortical neuronal spiking is highest at&#xD;
      sensorimotor alpha oscillation troughs and lowest at sensorimotor alpha oscillation peaks,&#xD;
      suggesting that cortical excitability is higher at sensorimotor alpha oscillation troughs&#xD;
      relative to peaks. We will address these questions using closed-loop transcranial magnetic&#xD;
      stimulation (TMS).&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      TMS is a potential adjunct therapy for post-stroke neurorehabilitation. So far, it has been&#xD;
      customarily applied uncoupled from brain oscillatory activity (as measured using EEG&#xD;
      waveforms), resulting in variability in the biological response to each stimulus, small&#xD;
      effect sizes and significant inter-individual variability. Brain oscillatory activity (i.e.,&#xD;
      EEG waveform oscillatory activity) in the alpha band (8-12 Hz) is linked to cortical&#xD;
      inhibition, motor function and cognitive processing, and therefore influences brain function.&#xD;
      Limitations in open-loop systems the rely on post-hoc trial sorting based on EEG state have&#xD;
      shown mixed results. For example, corticospinal excitability (as measured with TMS) in&#xD;
      healthy humans varies depending on the sensorimotor alpha oscillatory phase during which TMS&#xD;
      is delivered: corticospinal excitability is higher when TMS is delivered during sensorimotor&#xD;
      alpha oscillation troughs (i.e., maximum surface negativity) and lower when TMS is delivered&#xD;
      during sensorimotor alpha oscillation peaks (i.e., maximum surface positivity). One prior&#xD;
      closed-loop study showed only an effect of power but not phase angle on cortical&#xD;
      excitability, but using a similar setup, but we have replicated the finding of increased&#xD;
      cortical excitability during sensorimotor alpha troughs in young healthy adults. We therefore&#xD;
      aim to extend these findings to two new populations: healthy older adults (Experiment 1) and&#xD;
      patients with chronic stroke (Experiment 2). Previous studies have demonstrated that older&#xD;
      adults exhibit significant differences in motor cortical physiology compared to young adults,&#xD;
      so Experiment 1 will be performed to determine whether an association between sensorimotor&#xD;
      alpha oscillatory phase and corticospinal excitability is present in healthy aging.&#xD;
      Additionally, Experiment 2 will be performed to determine if the expected association between&#xD;
      sensorimotor alpha oscillatory phase and corticospinal excitability is also present after&#xD;
      chronic stroke. Importantly, acquiring information regarding how the aged and damaged brain&#xD;
      respond to EEG waveform oscillation-dependent closed-loop TMS will be critical for developing&#xD;
      more effective TMS-based (i.e., closed-loop) interventions. In both experiments, TMS delivery&#xD;
      will be timed to specific sensorimotor alpha oscillation phases. We expect the results of&#xD;
      this work to provide new insights into how corticospinal excitability is affected by&#xD;
      sensorimotor alpha oscillation phase in the aged and post-stroke brain, which could lead to&#xD;
      more effective use of sensorimotor alpha oscillation-dependent neuromodulatory TMS protocols&#xD;
      in the future.&#xD;
&#xD;
      Endpoints:&#xD;
&#xD;
      For both experiments, the primary outcome measure is corticospinal excitability. Exploratory&#xD;
      outcome measures include MEP amplitude variability, and TMS-induced oscillations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 11, 2018</start_date>
  <completion_date type="Anticipated">March 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>We will study if corticospinal excitability varies across different sensorimotor alpha EEG waveform oscillation phases in healthy older adults and chronic stroke patients.</measure>
    <time_frame>6 years</time_frame>
    <description>For both experiments, the primary outcome measure is corticospinal excitability. Exploratory outcome measures include MEP amplitude variability, and TMS-induced oscillations</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">52</enrollment>
  <condition>Healthy</condition>
  <condition>Stroke</condition>
  <condition>Normal Physiology</condition>
  <condition>Aging</condition>
  <arm_group>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <description>Healthy volunteers age 50 and older</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stroke patients</arm_group_label>
    <description>Stroke patients aged 18 and older</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Up to 24 older healthy volunteers (ages 50 and older) and up to 28 stroke patients (age 18&#xD;
        and older).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  Healthy older adults:&#xD;
&#xD;
               -  Age 50 and over&#xD;
&#xD;
               -  Willingness/ability to provide informed consent&#xD;
&#xD;
               -  In good general health as evidenced by ability to induce a motor evoked potential&#xD;
                  in the muscle target of the upper extremity, as evaluated during the TMS&#xD;
                  Screening&#xD;
&#xD;
        Stroke patients:&#xD;
&#xD;
          -  Age 18 and over&#xD;
&#xD;
          -  Unilateral or bilateral upper limb hemiparesis with the ability to voluntarily&#xD;
             contract a finger, hand, wrist, or elbow muscle in the affected arm(s)&#xD;
&#xD;
          -  Stroke onset &gt; 6 months prior to participation&#xD;
&#xD;
          -  Intact M1 sufficient to induce motor evoked potentials in the affected upper extremity&#xD;
             following ipsilesional TMS, as evaluated during the TMS Screening.&#xD;
&#xD;
          -  Willingness/ability to provide informed consent&#xD;
&#xD;
               -  If the investigator feels the individual s capacity to provide informed consent&#xD;
                  is questionable, the NIH Human Subjects Protection Unit (HSPU) will be requested&#xD;
                  to determine the individual s ability to consent.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Healthy older adults:&#xD;
&#xD;
               -  Presence of severe neurological or medical disorder (e.g. Parkinson s disease or&#xD;
                  multiple sclerosis)&#xD;
&#xD;
               -  History of seizures&#xD;
&#xD;
               -  Chronic use of antipsychotic drugs (e.g., chlorpromazine or clozapine),&#xD;
                  tri-cyclic or other anti-depressants, benzodiazepines, or prescription stimulants&#xD;
&#xD;
               -  TMS contraindications, such as:&#xD;
&#xD;
                    -  Pacemaker, implanted pump, stimulator, cochlear implant, or metal objects&#xD;
                       inside the eye or skull&#xD;
&#xD;
                    -  Diagnosed severe hearing loss&#xD;
&#xD;
               -  Current pregnancy&#xD;
&#xD;
               -  Staff from our section&#xD;
&#xD;
          -  Stroke patients:&#xD;
&#xD;
               -  Presence of severe neurological or medical disorder, other than stroke (e.g.&#xD;
                  Parkinson s disease or multiple sclerosis)&#xD;
&#xD;
               -  History of brainstem stroke&#xD;
&#xD;
               -  History of seizures&#xD;
&#xD;
               -  Chronic use of antipsychotic drugs (e.g., chlorpromazine or clozapine),&#xD;
                  benzodiazepines, or prescription stimulants&#xD;
&#xD;
               -  TMS contraindications, such as:&#xD;
&#xD;
                    -  Pacemaker, implanted pump, stimulator, cochlear implant, or metal objects&#xD;
                       inside the eye or skull&#xD;
&#xD;
                    -  Diagnosed severe hearing loss&#xD;
&#xD;
               -  Current pregnancy&#xD;
&#xD;
               -  Staff from our section&#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>Leonardo G Cohen, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Neurological Disorders and Stroke (NINDS)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Tasneem F Malik, C.R.N.P.</last_name>
    <phone>(301) 451-1335</phone>
    <email>tasneem.malik@nih.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Leonardo G Cohen, M.D.</last_name>
    <phone>(301) 496-9782</phone>
    <email>cohenl1@mail.nih.gov</email>
  </overall_contact_backup>
  <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>
    <status>Recruiting</status>
    <contact>
      <last_name>For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)</last_name>
      <phone>800-411-1222</phone>
      <phone_ext>TTY8664111010</phone_ext>
      <email>prpl@cc.nih.gov</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2017-N-0168.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>September 12, 2023</verification_date>
  <study_first_submitted>September 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <last_update_submitted>September 15, 2023</last_update_submitted>
  <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Stroke</keyword>
  <keyword>Natural History</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</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/NCT03288220
org study id: 170168
secondary id: 17-N-0168
nct id: NCT03288220
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Background:

      When people have a stroke, they often have difficulty moving their arms and hands.
      Transcranial magnetic stimulation (TMS) can improve how well people with and without stroke
      can move their arms and hands. But the effects of TMS are minor, and it doesn t work for
      everyone. Researchers want to study how to time brain stimulation so that the effects are
      more consistent.

      Objective:

      To understand how the brain responds to transcranial magnetic stimulation so that treatments
      for people with stroke can be improved.

      Eligibility:

      Adults ages 18 and older who had a stroke at least 6 months ago

      Healthy volunteers ages 50 and older

      Design:

      Participants will have up to 5 visits.

      At visit 1, participants will be screened with medical history and physical exam.
      Participants with stroke will also have TMS and surface electromyography (sEMG).

      For TMS, a brief electrical current will pass through a wire coil on the scalp. Participants
      may hear a click and feel a pull. Muscles may twitch. Participants may be asked to do simple
      movements during TMS.

      For sEMG, small electrodes will be attached to the skin and muscle activity will be recorded.

      At visit 2, participants will have magnetic resonance imaging (MRI). They will lie on a table
      that slides into a metal cylinder in a strong magnetic field. They will get earplugs for the
      loud noise.

      At visit 3, participants will have TMS, sEMG, and electroencephalography (EEG). For EEG,
      small electrodes on the scalp will record brainwaves. Participants will sit still, watch a
      movie, or do TMS.

      Participants may be asked to have 2 extra visits to redo procedures.
Study Description:

      We will study if corticospinal excitability (primary outcome measure) varies across different
      sensorimotor alpha electroencephalography (EEG) wave form oscillation phases in healthy older
      adults and chronic stroke patients. Sensorimotor cortical neuronal spiking is highest at
      sensorimotor alpha oscillation troughs and lowest at sensorimotor alpha oscillation peaks,
      suggesting that cortical excitability is higher at sensorimotor alpha oscillation troughs
      relative to peaks. We will address these questions using closed-loop transcranial magnetic
      stimulation (TMS).

      Objectives:

      TMS is a potential adjunct therapy for post-stroke neurorehabilitation. So far, it has been
      customarily applied uncoupled from brain oscillatory activity (as measured using EEG
      waveforms), resulting in variability in the biological response to each stimulus, small
      effect sizes and significant inter-individual variability. Brain oscillatory activity (i.e.,
      EEG waveform oscillatory activity) in the alpha band (8-12 Hz) is linked to cortical
      inhibition, motor function and cognitive processing, and therefore influences brain function.
      Limitations in open-loop systems the rely on post-hoc trial sorting based on EEG state have
      shown mixed results. For example, corticospinal excitability (as measured with TMS) in
      healthy humans varies depending on the sensorimotor alpha oscillatory phase during which TMS
      is delivered: corticospinal excitability is higher when TMS is delivered during sensorimotor
      alpha oscillation troughs (i.e., maximum surface negativity) and lower when TMS is delivered
      during sensorimotor alpha oscillation peaks (i.e., maximum surface positivity). One prior
      closed-loop study showed only an effect of power but not phase angle on cortical
      excitability, but using a similar setup, but we have replicated the finding of increased
      cortical excitability during sensorimotor alpha troughs in young healthy adults. We therefore
      aim to extend these findings to two new populations: healthy older adults (Experiment 1) and
      patients with chronic stroke (Experiment 2). Previous studies have demonstrated that older
      adults exhibit significant differences in motor cortical physiology compared to young adults,
      so Experiment 1 will be performed to determine whether an association between sensorimotor
      alpha oscillatory phase and corticospinal excitability is present in healthy aging.
      Additionally, Experiment 2 will be performed to determine if the expected association between
      sensorimotor alpha oscillatory phase and corticospinal excitability is also present after
      chronic stroke. Importantly, acquiring information regarding how the aged and damaged brain
      respond to EEG waveform oscillation-dependent closed-loop TMS will be critical for developing
      more effective TMS-based (i.e., closed-loop) interventions. In both experiments, TMS delivery
      will be timed to specific sensorimotor alpha oscillation phases. We expect the results of
      this work to provide new insights into how corticospinal excitability is affected by
      sensorimotor alpha oscillation phase in the aged and post-stroke brain, which could lead to
      more effective use of sensorimotor alpha oscillation-dependent neuromodulatory TMS protocols
      in the future.

      Endpoints:

      For both experiments, the primary outcome measure is corticospinal excitability. Exploratory
      outcome measures include MEP amplitude variability, and TMS-induced oscillations.
observational model: Cohort
time perspective: Prospective
measure: We will study if corticospinal excitability varies across different sensorimotor alpha EEG waveform oscillation phases in healthy older adults and chronic stroke patients.
time frame: 6 years
description: For both experiments, the primary outcome measure is corticospinal excitability. Exploratory outcome measures include MEP amplitude variability, and TMS-induced oscillations
arm group label: Healthy volunteers
description: Healthy volunteers age 50 and older
arm group label: Stroke patients
description: Stroke patients aged 18 and older
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: Leonardo G Cohen, M.D.
role: Principal Investigator
affiliation: National Institute of Neurological Disorders and Stroke (NINDS)
last name: Tasneem F Malik, C.R.N.P.
phone: (301) 451-1335
email: tasneem.malik@nih.gov
last name: Leonardo G Cohen, M.D.
phone: (301) 496-9782
email: cohenl1@mail.nih.gov
facility: 
status: Recruiting
contact: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2017-N-0168.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Sponsor
mesh term: Stroke