<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/NCT02188420</url>
  </required_header>
  <id_info>
    <org_study_id>DPT_PAS</org_study_id>
    <nct_id>NCT02188420</nct_id>
  </id_info>
  <brief_title>Finding an Optimal Latency for Paired Associative Stimulation in People With Chronic Stroke</brief_title>
  <official_title>Effect of Different Interpulse Intervals of Paired Associative Stimulation on Cortical Excitability in People With Chronic Stroke</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Minnesota</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      After a stroke, there is an exaggerated inhibitory influence from the non-stroke hemisphere&#xD;
      to the stroke hemisphere. Brain stimulation using repetitive transcranial magnetic&#xD;
      stimulation (rTMS) to the non-stroke hemisphere can decrease this inhibition. Paired&#xD;
      Associative Stimulation (PAS) may be a more effective way to produce this same inhibition, as&#xD;
      shown in healthy subjects. However, it is not known whether this will translate to people&#xD;
      with stroke. PAS consists of a peripheral nerve stimulus paired a short time later with a&#xD;
      cortical stimulus to change the excitability within the brain. Thus the investigators will&#xD;
      apply PAS to people with stroke, but the investigators need to first determine the most&#xD;
      effective interpulse interval (IPI) between the peripheral and cortical stimuli. Our research&#xD;
      question is which of three different IPIs is most effective in changing the excitability of&#xD;
      the brain.&#xD;
&#xD;
      The purpose of this study is to determine the optimal IPI between a peripheral nerve pulse&#xD;
      and a cortical stimulus that will be most effective in changing excitability of the brain in&#xD;
      people with chronic stroke. The investigators hypothesize that the cortical excitability of&#xD;
      the nonstroke hemisphere will be most inhibited with the latency-5ms condition.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Numerous PAS studies have been done in healthy subjects and all have been done safely. The&#xD;
      proper interpulse interval in healthy individuals between the peripheral nerve stimulus and&#xD;
      the cortical stimulus is known to be &quot;latency-5ms.&quot; However, this may be different in&#xD;
      individuals with stroke.&#xD;
&#xD;
      Specific Aim: what is the optimal interpulse interval to achieve the maximum inhibitory&#xD;
      effect in the nonstroke hemisphere?&#xD;
&#xD;
      We will recruit three subjects with chronic stroke. Electroencephalography (EEG) will be used&#xD;
      to determine the latency between the peripheral nerve stimulus and the sensory evoked&#xD;
      potential in each subject. We will then assess the following IPIs on each subject in a random&#xD;
      order: &quot;latency&quot; - 3ms, -5ms and -7ms. There will be a fourth condition of &quot;latency&quot; + 100ms&#xD;
      (known to have no effect) to be used as a control. The washout period will be at least one&#xD;
      week between each of these conditions.&#xD;
&#xD;
      The optimal IPI will be determined from these tests by comparing single pulse transcranial&#xD;
      magnetic stimulation (TMS) measures for cortical excitability. Prior to each treatment, each&#xD;
      subject will receive 20 single pulse cortical stimuli to serve as pretest data. The post&#xD;
      tests for each condition will consist of 20 single pulse cortical stimuli at 0, 5, 10, 15,&#xD;
      30, 45 and 60 minutes after the PAS condition. Data analysis will consist of a single-subject&#xD;
      analysis with the two standard deviation bandwidth method of each post-test compared to&#xD;
      pre-test.&#xD;
&#xD;
      We hypothesize that there will be no adverse advents and that this optimal IPI will be&#xD;
      &quot;latency&quot;-5ms.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">December 2016</completion_date>
  <primary_completion_date type="Actual">May 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in cortical excitability using single TMS pulses</measure>
    <time_frame>Change from pretest (immediately prior to PAS application) to posttest which will occur over the 60 minutes that follow PAS application.</time_frame>
    <description>Assess average size of 20 motor evoked potentials via electromyography (EMG) signal resulting from single TMS pulses to the motor cortex. Measurements taken before and after paired associative stimulation treatment at each session.</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">3</enrollment>
  <condition>Stroke</condition>
  <arm_group>
    <arm_group_label>Latency minus 3ms</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of (&quot;Latency&quot; - 3ms) where &quot;latency&quot; refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Latency minus 5ms</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of (&quot;Latency&quot; - 5ms) where &quot;latency&quot; refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Latency minus 7ms</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of (&quot;Latency&quot; - 7ms) where &quot;latency&quot; refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Latency plus 100ms</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of (&quot;Latency&quot; + 100ms), known to have no effect, where &quot;latency&quot; refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial Magnetic Stimulation (Magstim)</intervention_name>
    <arm_group_label>Latency minus 3ms</arm_group_label>
    <arm_group_label>Latency minus 5ms</arm_group_label>
    <arm_group_label>Latency minus 7ms</arm_group_label>
    <arm_group_label>Latency plus 100ms</arm_group_label>
    <other_name>TMS</other_name>
    <other_name>Magstim</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  stroke (ischemic or hemorrhagic) of greater than 6 months duration&#xD;
&#xD;
          -  impairment in the paretic hand&#xD;
&#xD;
          -  over 18 years old&#xD;
&#xD;
          -  male or female&#xD;
&#xD;
          -  on mini mental status exam must have score of 22 or higher&#xD;
&#xD;
          -  must have elicitable motor evoked potential (MEP)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  seizure within the past two years&#xD;
&#xD;
          -  receptive aphasia&#xD;
&#xD;
          -  epileptogenic medication&#xD;
&#xD;
          -  major psychiatric disorder&#xD;
&#xD;
          -  other interfering comorbidities&#xD;
&#xD;
          -  pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kate Frost, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Minnesota Clinical and Translational Science Institute</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55414</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>June 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 11, 2014</study_first_posted>
  <last_update_submitted>February 23, 2016</last_update_submitted>
  <last_update_submitted_qc>February 23, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 24, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PAS</keyword>
  <keyword>TMS</keyword>
  <keyword>Stroke</keyword>
  <keyword>Paired Associative Stimulation</keyword>
  <keyword>Transcranial Magnetic Stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>May 9, 2017</submitted>
    <returned>June 9, 2017</returned>
    <submitted>October 9, 2017</submitted>
    <returned>November 8, 2017</returned>
    <submitted>November 14, 2017</submitted>
    <returned>December 14, 2017</returned>
    <submitted>January 18, 2018</submitted>
    <returned>February 13, 2018</returned>
    <submitted>May 21, 2019</submitted>
    <returned>July 22, 2019</returned>
    <submitted>October 30, 2019</submitted>
    <returned>November 19, 2019</returned>
  </pending_results>
  <!-- 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/NCT02188420
org study id: DPT_PAS
nct id: NCT02188420
lead sponsor: 
has dmc: No
After a stroke, there is an exaggerated inhibitory influence from the non-stroke hemisphere
      to the stroke hemisphere. Brain stimulation using repetitive transcranial magnetic
      stimulation (rTMS) to the non-stroke hemisphere can decrease this inhibition. Paired
      Associative Stimulation (PAS) may be a more effective way to produce this same inhibition, as
      shown in healthy subjects. However, it is not known whether this will translate to people
      with stroke. PAS consists of a peripheral nerve stimulus paired a short time later with a
      cortical stimulus to change the excitability within the brain. Thus the investigators will
      apply PAS to people with stroke, but the investigators need to first determine the most
      effective interpulse interval (IPI) between the peripheral and cortical stimuli. Our research
      question is which of three different IPIs is most effective in changing the excitability of
      the brain.

      The purpose of this study is to determine the optimal IPI between a peripheral nerve pulse
      and a cortical stimulus that will be most effective in changing excitability of the brain in
      people with chronic stroke. The investigators hypothesize that the cortical excitability of
      the nonstroke hemisphere will be most inhibited with the latency-5ms condition.
Numerous PAS studies have been done in healthy subjects and all have been done safely. The
      proper interpulse interval in healthy individuals between the peripheral nerve stimulus and
      the cortical stimulus is known to be "latency-5ms." However, this may be different in
      individuals with stroke.

      Specific Aim: what is the optimal interpulse interval to achieve the maximum inhibitory
      effect in the nonstroke hemisphere?

      We will recruit three subjects with chronic stroke. Electroencephalography (EEG) will be used
      to determine the latency between the peripheral nerve stimulus and the sensory evoked
      potential in each subject. We will then assess the following IPIs on each subject in a random
      order: "latency" - 3ms, -5ms and -7ms. There will be a fourth condition of "latency" + 100ms
      (known to have no effect) to be used as a control. The washout period will be at least one
      week between each of these conditions.

      The optimal IPI will be determined from these tests by comparing single pulse transcranial
      magnetic stimulation (TMS) measures for cortical excitability. Prior to each treatment, each
      subject will receive 20 single pulse cortical stimuli to serve as pretest data. The post
      tests for each condition will consist of 20 single pulse cortical stimuli at 0, 5, 10, 15,
      30, 45 and 60 minutes after the PAS condition. Data analysis will consist of a single-subject
      analysis with the two standard deviation bandwidth method of each post-test compared to
      pre-test.

      We hypothesize that there will be no adverse advents and that this optimal IPI will be
      "latency"-5ms.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Single (Participant)
measure: Change in cortical excitability using single TMS pulses
time frame: Change from pretest (immediately prior to PAS application) to posttest which will occur over the 60 minutes that follow PAS application.
description: Assess average size of 20 motor evoked potentials via electromyography (EMG) signal resulting from single TMS pulses to the motor cortex. Measurements taken before and after paired associative stimulation treatment at each session.
arm group label: Latency minus 3ms
arm group type: Experimental
description: Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 3ms) where "latency" refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG.
arm group label: Latency minus 5ms
arm group type: Experimental
description: Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 5ms) where "latency" refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG.
arm group label: Latency minus 7ms
arm group type: Experimental
description: Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" - 7ms) where "latency" refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG.
arm group label: Latency plus 100ms
arm group type: Active Comparator
description: Transcranial Magnetic Stimulation will be applied to the primary motor cortex at the interstimulus interval of ("Latency" + 100ms), known to have no effect, where "latency" refers to the amount of time for the arrival of a sensory evoked potential as determined by EEG.
intervention type: Device
intervention name: Transcranial Magnetic Stimulation (Magstim)
arm group label: Latency minus 3ms
arm group label: Latency minus 5ms
arm group label: Latency minus 7ms
arm group label: Latency plus 100ms
other name: TMS
other name: Magstim
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kate Frost, MS
role: Principal Investigator
affiliation: University of Minnesota
facility: 
country: United States
responsible party type: Sponsor
mesh term: Stroke
submitted: May 9, 2017
returned: June 9, 2017
submitted: October 9, 2017
returned: November 8, 2017
submitted: November 14, 2017
returned: December 14, 2017
submitted: January 18, 2018
returned: February 13, 2018
submitted: May 21, 2019
returned: July 22, 2019
submitted: October 30, 2019
returned: November 19, 2019