<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/NCT03773406</url>
  </required_header>
  <id_info>
    <org_study_id>90IFRE0020</org_study_id>
    <nct_id>NCT03773406</nct_id>
  </id_info>
  <brief_title>Timing of Transcranial Direct Current Stimulation (tDCS) Combined With Speech and Language Therapy (SLT)</brief_title>
  <official_title>Timing of Transcranial Direct Current Stimulation (tDCS) Combined With Speech and Language Therapy (SLT): An Intervention Development Study for Aphasia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shirley Ryan AbilityLab</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Disability, Independent Living, and Rehabilitation Research</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Shirley Ryan AbilityLab</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Aphasia is an acquired (typically left-hemisphere) multi-modality disturbance of language&#xD;
      that impacts around 2 million people in the USA. Aphasia impacts language production and&#xD;
      comprehension as well as reading and writing. The ramifications of aphasia extend beyond&#xD;
      language impairment to negatively impacting a person's social, vocational, and recreational&#xD;
      activities. Currently, the most effective way to treat aphasia is with speech-language&#xD;
      therapy (SLT). However, even if SLT is intensive, persons with aphasia are left with residual&#xD;
      language delays. Recent research suggests that pairing SLT with transcranial direct current&#xD;
      stimulation (tDCS) a non-invasive, safe, low-cost form of brain stimulation may aid language&#xD;
      recovery in persons with aphasia. However, results from tDCS studies are inconclusive. The&#xD;
      success of tDCS in combination with SLT could depend on the timing of tDCS since tDCS-induced&#xD;
      effects depend on the neuronal state of the brain-networks at the time of the stimulation. In&#xD;
      this study, the differential impact of tDCS before behavioral SLT (offline-before therapy),&#xD;
      tDCS after SLT (offline-after therapy), and tDCS concurrently with SLT (online) on functional&#xD;
      language recovery in persons with aphasia will be investigated. Sham tDCS (i.e., SLT alone)&#xD;
      as a control group will also be included in the study. The investigators hypothesize that&#xD;
      both offline and online tDCS will improve language functioning than sham tDCS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      tDCS Implementation:&#xD;
&#xD;
      2mA of direct current for 20 minutes will be delivered using a constant current stimulator&#xD;
      via two electrodes in saline soaked sponges. To stimulate the left angular gyrus, a cathodal&#xD;
      electrode inside a saline soaked sponge (5 x 3cm) will be placed over the CP5 according to&#xD;
      the 10-20 international system for EEG electrode placement. The electrodes will be secured in&#xD;
      position by a custom-built EEG cap that will be marked with the location for angular gyrus.&#xD;
      The investigators will then confirm that the cathodal electrode is over the left angular&#xD;
      through the use of neuronavigation. The &quot;return&quot; anode electrode will be placed in a saline&#xD;
      soaked sponge (5 x 5cm) on the center of the supraorbital region.&#xD;
&#xD;
      At the beginning of the tDCS, current will slowly ram-up during the first few seconds until&#xD;
      it reaches 2mA. The ramp-up process will acclimate the participants to tDCS-induced&#xD;
      sensations (e.g., itching). At the end of the tDCS sessions, current will slowly ramp down in&#xD;
      the last few seconds to 0mA. The total duration of the 2mA current will be maintained for 20&#xD;
      minutes. For sham stimulation, the investigators will place the electrodes in the same&#xD;
      location as the real tDCS groups with stimulation ending after few seconds. The brief&#xD;
      stimulation will produce tDCS-induced sensations so that participants will not be aware when&#xD;
      the tDCS stopped delivering direct current&#xD;
&#xD;
      Speech-Language Treatment:&#xD;
&#xD;
      Standard-of-care treatment - script training will be used to provide SLT to our participants.&#xD;
      The treatment will be delivered via a computer program, Aphasia Scripts ®, whereby a virtual&#xD;
      therapist interactively guides the participants through treatment steps. Scripts will be five&#xD;
      to ten sentences and developed from common templates about topics relevant to daily life&#xD;
      (e.g., asking questions at the grocery store, ordering in a restaurant). The advantage of&#xD;
      using a computer program instead of a human therapist is that it removes extraneous variables&#xD;
      associated with human therapists (e.g., different levels of encouragement) and this, together&#xD;
      with the use of script templates, ensures treatment fidelity across participants.&#xD;
&#xD;
      Duration of an individual subject's participation in the study:&#xD;
&#xD;
      Subjects will be requested to come for baseline sessions (3 to 4 hours) before the actual&#xD;
      experiment. The baseline assessments may be done over two visits. In the baseline session the&#xD;
      subjects' aphasia severity will be assessed. The participants will also perform baseline&#xD;
      tasks of language and cognition in this session. Subjects will then participate in 3 weeks of&#xD;
      tDCS and SLT (i.e., 15 sessions). The sessions will consist of 40 minutes of SLT and 20&#xD;
      minutes of tDCS. Subjects will be asked to return for an assessment immediately following the&#xD;
      end of treatment and for follow-up testing after 4 and 8 weeks. Therefore, total number of&#xD;
      visits will be 19-23 sessions (depending on how many visits are needed for the assessments)&#xD;
      over a period of three months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 3, 2019</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2022</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in trained conversational script.</measure>
    <time_frame>3 weeks.</time_frame>
    <description>Changes in accuracy and rate of production on a trained conversational script from pre to post-treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in untrained conversational script</measure>
    <time_frame>3 weeks</time_frame>
    <description>Changes in accuracy and rate of production on an untrained conversational script from pre to post-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Aphasia Quotient (AQ) of Western Aphasia Battery-Revised (WAB-R)</measure>
    <time_frame>3 weeks</time_frame>
    <description>Changes in WAB-R AQ from pre and post treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maintenance of trained conversational script</measure>
    <time_frame>7 weeks</time_frame>
    <description>Accuracy and rate of production of trained conversational script at 4 weeks post-treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maintenance of trained conversational script</measure>
    <time_frame>11 weeks</time_frame>
    <description>Accuracy and rate of production of trained conversational script at 8 weeks post-treatment</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">48</enrollment>
  <condition>Aphasia</condition>
  <arm_group>
    <arm_group_label>Offline tDCS-before therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive 20 minutes of tDCS prior to the 40 minute speech-language therapy session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Offline tDCS-after therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive 20 minutes of tDCS after the 40 minute speech-language therapy session.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Online tDCS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>tDCS will be applied at the beginning of the 40 minute speech-language therapy session and will last for 20 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham tDCS</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Sham tDCS will be applied at the beginning of the 40 minute speech-language therapy session.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Offline tDCS-before therapy</intervention_name>
    <description>Direct current stimulation will be delivered using a battery-driven constant current stimulator. 2mA of direct current will be applied for 20 minutes to the angular gyrus region of the brain. We will use a standard-of-care treatment - script training - to provide speech-language therapy to our subjects. The scripting treatment will be delivered by a computer program that provides script training in an interactive conversational context.</description>
    <arm_group_label>Offline tDCS-before therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham tDCS</intervention_name>
    <description>Stimulation will be given for a total 30 seconds (including ramp-up and ramp-down of current) and then the tDCS device will be turned off. The brief stimulation will produce tDCS-induced sensation so that participants will not be aware when the tDCS was turned off .We will use standard-of-care treatment - script training - to provide speech-language therapy to our subjects. The scripting treatment will be delivered by a computer program that provides script training in an interactive conversational context.</description>
    <arm_group_label>Sham tDCS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Offline tDCS-after therapy</intervention_name>
    <description>Direct current stimulation will be delivered using a battery-driven constant current stimulator. 2mA of direct current will be applied for 20 minutes to the angular gyrus region of the brain. We will use a standard-of-care treatment - script training - to provide speech-language therapy to our subjects. The scripting treatment will be delivered by a computer program that provides script training in an interactive conversational context.</description>
    <arm_group_label>Offline tDCS-after therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Online tDCS</intervention_name>
    <description>Direct current stimulation will be delivered using a battery-driven constant current stimulator. 2mA of direct current will be applied for 20 minutes to the angular gyrus region of the brain. We will use a standard-of-care treatment - script training - to provide speech-language therapy to our subjects. The scripting treatment will be delivered by a computer program that provides script training in an interactive conversational context.</description>
    <arm_group_label>Online tDCS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men or women with diagnosis of fluent or non-fluent aphasia subsequent to a&#xD;
             left-hemisphere infarct(s) that is confirmed by a MRI or CT scan&#xD;
&#xD;
          -  Aphasia quotient on the WAB of 35-85&#xD;
&#xD;
          -  At least 6 months post onset of aphasia (this is beyond the stage of spontaneous&#xD;
             recovery)&#xD;
&#xD;
          -  18- 80 years of age&#xD;
&#xD;
          -  Premorbidly fluent in English&#xD;
&#xD;
          -  Premorbidly right-hand dominant per the Edinburg Handedness Inventory&#xD;
&#xD;
          -  Visual acuity of 20/40 corrected&#xD;
&#xD;
          -  Auditory acuity no worse than 30 dB HL on pure tone testing, aided in the better ear.&#xD;
&#xD;
          -  Education greater than 12th grade&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any other neurological condition (other than cerebral vascular disease) that could&#xD;
             impact language and cognition such as Alzheimer's disease, Parkinson's disease,&#xD;
             primary progressive aphasia, and traumatic brain injury&#xD;
&#xD;
          -  Active substance use&#xD;
&#xD;
          -  Individuals with epilepsy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Leora Cherney, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shirley Ryan AbilityLab</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Leora Cherney, PhD</last_name>
    <phone>312-238-1117</phone>
    <email>lcherney@sralab.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sameer Ashaie, PhD</last_name>
    <phone>312-238-6163</phone>
    <email>sameer.ashaie@northwestern.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Shirley Ryan AbilityLab</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Leora Cherney, PhD</last_name>
      <phone>312-238-1117</phone>
      <email>lcherney@sralab.org</email>
    </contact>
    <contact_backup>
      <last_name>Sameer Ashaie, PhD</last_name>
      <phone>312-238-6163</phone>
      <email>sameer.ashaie@northwestern.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Leora Cherney, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>July 24, 2022</last_update_submitted>
  <last_update_submitted_qc>July 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shirley Ryan AbilityLab</investigator_affiliation>
    <investigator_full_name>Leora Cherney</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Aphasia, tDCS, Script training, Functional language, Naming</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aphasia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT03773406
org study id: 90IFRE0020
nct id: NCT03773406
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
Aphasia is an acquired (typically left-hemisphere) multi-modality disturbance of language
      that impacts around 2 million people in the USA. Aphasia impacts language production and
      comprehension as well as reading and writing. The ramifications of aphasia extend beyond
      language impairment to negatively impacting a person's social, vocational, and recreational
      activities. Currently, the most effective way to treat aphasia is with speech-language
      therapy (SLT). However, even if SLT is intensive, persons with aphasia are left with residual
      language delays. Recent research suggests that pairing SLT with transcranial direct current
      stimulation (tDCS) a non-invasive, safe, low-cost form of brain stimulation may aid language
      recovery in persons with aphasia. However, results from tDCS studies are inconclusive. The
      success of tDCS in combination with SLT could depend on the timing of tDCS since tDCS-induced
      effects depend on the neuronal state of the brain-networks at the time of the stimulation. In
      this study, the differential impact of tDCS before behavioral SLT (offline-before therapy),
      tDCS after SLT (offline-after therapy), and tDCS concurrently with SLT (online) on functional
      language recovery in persons with aphasia will be investigated. Sham tDCS (i.e., SLT alone)
      as a control group will also be included in the study. The investigators hypothesize that
      both offline and online tDCS will improve language functioning than sham tDCS.
tDCS Implementation:

      2mA of direct current for 20 minutes will be delivered using a constant current stimulator
      via two electrodes in saline soaked sponges. To stimulate the left angular gyrus, a cathodal
      electrode inside a saline soaked sponge (5 x 3cm) will be placed over the CP5 according to
      the 10-20 international system for EEG electrode placement. The electrodes will be secured in
      position by a custom-built EEG cap that will be marked with the location for angular gyrus.
      The investigators will then confirm that the cathodal electrode is over the left angular
      through the use of neuronavigation. The "return" anode electrode will be placed in a saline
      soaked sponge (5 x 5cm) on the center of the supraorbital region.

      At the beginning of the tDCS, current will slowly ram-up during the first few seconds until
      it reaches 2mA. The ramp-up process will acclimate the participants to tDCS-induced
      sensations (e.g., itching). At the end of the tDCS sessions, current will slowly ramp down in
      the last few seconds to 0mA. The total duration of the 2mA current will be maintained for 20
      minutes. For sham stimulation, the investigators will place the electrodes in the same
      location as the real tDCS groups with stimulation ending after few seconds. The brief
      stimulation will produce tDCS-induced sensations so that participants will not be aware when
      the tDCS stopped delivering direct current

      Speech-Language Treatment:

      Standard-of-care treatment - script training will be used to provide SLT to our participants.
      The treatment will be delivered via a computer program, Aphasia Scripts ®, whereby a virtual
      therapist interactively guides the participants through treatment steps. Scripts will be five
      to ten sentences and developed from common templates about topics relevant to daily life
      (e.g., asking questions at the grocery store, ordering in a restaurant). The advantage of
      using a computer program instead of a human therapist is that it removes extraneous variables
      associated with human therapists (e.g., different levels of encouragement) and this, together
      with the use of script templates, ensures treatment fidelity across participants.

      Duration of an individual subject's participation in the study:

      Subjects will be requested to come for baseline sessions (3 to 4 hours) before the actual
      experiment. The baseline assessments may be done over two visits. In the baseline session the
      subjects' aphasia severity will be assessed. The participants will also perform baseline
      tasks of language and cognition in this session. Subjects will then participate in 3 weeks of
      tDCS and SLT (i.e., 15 sessions). The sessions will consist of 40 minutes of SLT and 20
      minutes of tDCS. Subjects will be asked to return for an assessment immediately following the
      end of treatment and for follow-up testing after 4 and 8 weeks. Therefore, total number of
      visits will be 19-23 sessions (depending on how many visits are needed for the assessments)
      over a period of three months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Change in trained conversational script.
time frame: 3 weeks.
description: Changes in accuracy and rate of production on a trained conversational script from pre to post-treatment.
measure: Change in untrained conversational script
time frame: 3 weeks
description: Changes in accuracy and rate of production on an untrained conversational script from pre to post-treatment.
measure: Change in the Aphasia Quotient (AQ) of Western Aphasia Battery-Revised (WAB-R)
time frame: 3 weeks
description: Changes in WAB-R AQ from pre and post treatment.
measure: Maintenance of trained conversational script
time frame: 7 weeks
description: Accuracy and rate of production of trained conversational script at 4 weeks post-treatment
measure: Maintenance of trained conversational script
time frame: 11 weeks
description: Accuracy and rate of production of trained conversational script at 8 weeks post-treatment
arm group label: Offline tDCS-before therapy
arm group type: Active Comparator
description: Participants will receive 20 minutes of tDCS prior to the 40 minute speech-language therapy session.
arm group label: Offline tDCS-after therapy
arm group type: Active Comparator
description: Participants will receive 20 minutes of tDCS after the 40 minute speech-language therapy session.
arm group label: Online tDCS
arm group type: Active Comparator
description: tDCS will be applied at the beginning of the 40 minute speech-language therapy session and will last for 20 minutes.
arm group label: Sham tDCS
arm group type: Sham Comparator
description: Sham tDCS will be applied at the beginning of the 40 minute speech-language therapy session.
intervention type: Device
intervention name: Offline tDCS-before therapy
description: Direct current stimulation will be delivered using a battery-driven constant current stimulator. 2mA of direct current will be applied for 20 minutes to the angular gyrus region of the brain. We will use a standard-of-care treatment - script training - to provide speech-language therapy to our subjects. The scripting treatment will be delivered by a computer program that provides script training in an interactive conversational context.
arm group label: Offline tDCS-before therapy
intervention type: Device
intervention name: Sham tDCS
description: Stimulation will be given for a total 30 seconds (including ramp-up and ramp-down of current) and then the tDCS device will be turned off. The brief stimulation will produce tDCS-induced sensation so that participants will not be aware when the tDCS was turned off .We will use standard-of-care treatment - script training - to provide speech-language therapy to our subjects. The scripting treatment will be delivered by a computer program that provides script training in an interactive conversational context.
arm group label: Sham tDCS
intervention type: Device
intervention name: Offline tDCS-after therapy
description: Direct current stimulation will be delivered using a battery-driven constant current stimulator. 2mA of direct current will be applied for 20 minutes to the angular gyrus region of the brain. We will use a standard-of-care treatment - script training - to provide speech-language therapy to our subjects. The scripting treatment will be delivered by a computer program that provides script training in an interactive conversational context.
arm group label: Offline tDCS-after therapy
intervention type: Device
intervention name: Online tDCS
description: Direct current stimulation will be delivered using a battery-driven constant current stimulator. 2mA of direct current will be applied for 20 minutes to the angular gyrus region of the brain. We will use a standard-of-care treatment - script training - to provide speech-language therapy to our subjects. The scripting treatment will be delivered by a computer program that provides script training in an interactive conversational context.
arm group label: Online tDCS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Leora Cherney, PhD
role: Principal Investigator
affiliation: Shirley Ryan AbilityLab
last name: Leora Cherney, PhD
phone: 312-238-1117
email: lcherney@sralab.org
last name: Sameer Ashaie, PhD
phone: 312-238-6163
email: sameer.ashaie@northwestern.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Shirley Ryan AbilityLab
investigator full name: Leora Cherney
investigator title: Principal Investigator
mesh term: Aphasia
sharing ipd: Undecided