<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/NCT02226796</url>
  </required_header>
  <id_info>
    <org_study_id>1506M73043</org_study_id>
    <nct_id>NCT02226796</nct_id>
  </id_info>
  <brief_title>Transcranial Direct Stimulation (tDCS) and Behavioral Intervention in Aphasia</brief_title>
  <official_title>Effects of a Combination of Transcranial Direct Stimulation (tDCS) and Behavioral Intervention in Non-fluent Aphasia</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      We hypothesize patients who have difficulty with word recall (naming pictures) due to a&#xD;
      stroke will experience greater benefit in word recall after receiving a combination of&#xD;
      transcranial direct current stimulation (tDCS) and traditional behavioral treatment. This&#xD;
      study will investigate the effects of the timing of tDCS in relationship to the behavioral&#xD;
      treatment to determine the most optimal protocol. Transcranial direct current stimulation&#xD;
      involves placing two electrodes on your scalp and sending a very small electrical current to&#xD;
      excite the brain cells of the target site.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Specific Aims Aim 1: Identify and quantify the effects of a-tDCS to the left dorsolateral&#xD;
      prefrontal cortex (DLPFC) in conjunction with intensive behavioral treatment on naming in&#xD;
      non-fluent aphasia. a-tDCS (2mA for 20 minutes) will be applied over the left DLPFC with&#xD;
      cathode over the right orbit. Pre and post treatment behavioral measures of naming and&#xD;
      working memory will be used to quantify and compare differences. Hypothesis 1: a-tDCS will&#xD;
      result in improvements in naming accuracy, naming response times, and working memory (WM) in&#xD;
      participants with non-fluent aphasia.&#xD;
&#xD;
      Aim 2: Compare the effects of a-tDCS applied to the left DLPFC before behavioral treatment to&#xD;
      during behavioral treatment in non-fluent aphasia. a-tDCS (2mA for 20 minutes) will be&#xD;
      applied over the left DLPFC with cathode over the right orbit. Pre and post treatment&#xD;
      behavioral measures of naming and working memory will be used to quantify and compare&#xD;
      functional differences between conditions. Hypothesis 1: a-tDCS to the DLPFC during treatment&#xD;
      will result in a greater improvement of naming accuracy, naming response time and WM in&#xD;
      participants with non-fluent aphasia.&#xD;
&#xD;
      Significance The findings from the proposed study will lay the foundation for a larger&#xD;
      clinical trial which will in turn have a significant impact on individuals with aphasia given&#xD;
      that naming deficits are a common symptom in this population. As the presence of naming&#xD;
      deficits has a negative relationship to emotional well-being and functional communication&#xD;
      26-30, treatment that improves naming deficits will positively influence quality of life in&#xD;
      many of these individuals. The approach taken to remediate naming deficits in aphasia is to&#xD;
      treat impaired WM systems on the premise that certain cognitive processes underlie linguistic&#xD;
      functions in aphasia. This approach represents a departure from most behavioral-based naming&#xD;
      treatment approach, but reflects a growing recognition that WM systems in individuals with&#xD;
      aphasia impact their linguistic performance 5, 31. The addition of a-tDCS as a&#xD;
      neuromodulation tool to increase cortical excitability (upregulate) the working memory center&#xD;
      to target naming is a novel approach. In addition, this study will further elucidate the&#xD;
      optimal timing of a-tDCS in order to achieve the most beneficial outcomes, which have not yet&#xD;
      been reported. These findings, along with other related studies, will shape future clinical&#xD;
      practice guidelines as more studies adopt a concurrent cognitive-linguistic approach to treat&#xD;
      linguistic deficits in aphasia.&#xD;
&#xD;
      Design &amp; Methodology Participants. Four individuals with aphasia will be recruited. These&#xD;
      participants must meet the following inclusionary/exclusionary criteria: a) completion of&#xD;
      high school or GED; b) normal or corrected-to-normal vision; c) adequate hearing acuity for&#xD;
      1:1 conversational exchanges; d) use of English as primary language; e) a vascular lesion in&#xD;
      the dominant left hemisphere verified by an MRI scan within six months of the start of the&#xD;
      study. These participants must also meet the following exclusionary criteria: a) no previous&#xD;
      history of neurological- or psychiatric-based illnesses or disease, language or learning&#xD;
      disabilities, or alcohol/substance abuse; b) no history of seizures; c) no metal implants in&#xD;
      the head (except dental fillings); d) no lesion in the left DLPFC confirmed by MRI; e) no&#xD;
      current pregnancy. Pre-Test Behavioral Measures. Participants will be seen between 2-3&#xD;
      sessions to undergo comprehensive cognitive-linguistic testing prior to initiation of&#xD;
      treatment. Testing will take place at the University of Minnesota (UMN) Clinical&#xD;
      Translational Science Institute (CTSI). Behavioral test measures will include the WAB 32 in&#xD;
      order to obtain the WAB Aphasia Quotient (WAB AQ), Boston Naming Test (BNT) 33 and the&#xD;
      Apraxia Battery for Adults (ABA-2) 34. The WAB AQ will provide a general classification of&#xD;
      aphasia subtype, scores from the BNT will provide the level of severity of naming impairment,&#xD;
      and ABA-2 performance will be used to assess severity of apraxia of speech (AoS). To assess&#xD;
      the integrity of the phonological store, participants will be tested for the effects of&#xD;
      phonological similarity using both auditory and visual presentation 35, 36. To assess the&#xD;
      integrity of subvocal rehearsal processes, participants will be tested for the effects of&#xD;
      word length on both auditory and visual span 37; the effects of articulatory suppression on&#xD;
      recall performance 37, 38; and rhyme judgments 39-41. Protocols that have been adapted for&#xD;
      individuals with aphasia will be followed42-45. These tests will be used to distinguish&#xD;
      behavioral evidence of deficient subvocal rehearsal processes from deficient phonological&#xD;
      short-term store. Individuals with a range of moderate to moderately severe nonfluent&#xD;
      aphasia, a range of moderate to moderately severe anomia, and a range of mild to no AoS will&#xD;
      be chosen for the study. Baseline probes will also be obtained prior to the initiation of the&#xD;
      study. Stability of baseline performance, defined as no more than 20% difference between&#xD;
      scores,will be obtained over three consecutive sessions in order to establish experimental&#xD;
      control. Post-Test Behavioral Measures. Participants will also be seen for post-treatment&#xD;
      testing following the implementation of the treatment protocol. Testing will take place in&#xD;
      the participant's home. Post-treatment behavioral measures will include BNT, the ABA-2, WM&#xD;
      tasks, and naming treatment and control items. It is anticipated that only one session will&#xD;
      be needed for post-treatment testing. An adverse events survey will also be provided to&#xD;
      assess the participant's level of discomfort during use of tDCS. tDCS Protocol. Each&#xD;
      participant will be seated comfortably in a chair. A swim cap will be placed on the&#xD;
      participant's head to identify cranial landmarks for accurate electrode placement. The area&#xD;
      referred to as F3 by the International 10/20 system for electroencephalogram electrode&#xD;
      placement46 has been established as the optimal location for targeting the left DLPFC25,&#xD;
      47-49. The F3 region will be located by marking the vertex (the midpoint between left and&#xD;
      right tragus and midpoint between nasion and inion), measuring the head circumference. When&#xD;
      these measurements are entered into the Beam F3 Locator Software50, additional values are&#xD;
      provided to reliably identify the location of F3. Once F3 has been established, two saline&#xD;
      soaked surface sponge electrodes (352cm) will be prepared and placed. For optimal anodal&#xD;
      stimulation to the DLPFC, the anode will be placed over F3 and the cathode will be placed&#xD;
      over the right supraorbital region23, 24, 47, 48. A current of 2mA will be delivered for 20&#xD;
      minutes 24 by a multichannel transcranial current stimulator (Starstim, Neuroelectrics&#xD;
      Corporation; Cambridge, MA). a-tDCS will be applied before and during behavioral treatment in&#xD;
      the design specified below.&#xD;
&#xD;
      Treatment Design. Two treatment conditions will be presented in a counter-balanced order in a&#xD;
      cross-over design. The non-prime (NONPRIME) condition will consist of 40 minutes of naming&#xD;
      treatment only, followed by an additional 20 minutes of concurrent naming treatment with&#xD;
      a-tDCS. The primed (PRIME) condition will consist of presentation of a-tDCS for 20 minutes&#xD;
      prior to naming treatment, while the subject sits quietly and comfortably in a chair. After&#xD;
      the 20-minute priming period, the a-tDCS will be removed and the participant will receive&#xD;
      naming treatment for 60 minutes. Both conditions will be presented over four consecutive&#xD;
      days. Two participants will receive NON-PRIME-PRIME sequence, with a one-month washout period&#xD;
      between the two conditions. Two other participants will receive PRIME-NON-PRIME sequence,&#xD;
      with a one-month washout period between the two conditions. Naming reaction time will be&#xD;
      immediately evaluated after each treatment day.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2015</start_date>
  <completion_date type="Actual">December 1, 2018</completion_date>
  <primary_completion_date type="Actual">December 1, 2018</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>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Naming Reaction Time</measure>
    <time_frame>40 minutes</time_frame>
    <description>Participants are shown one or 3 possible banks of pictures balanced for phonemic complexity which are randomly assigned to prevent learning effect. Each bank contains 15 items. Time to recall is measured using a stop watch. The mean time to recall across all items is calculated and reported in milliseconds. The smaller the number, the faster / better the reaction time is.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Naming Accuracy</measure>
    <time_frame>40 minutes</time_frame>
    <description>Participants are shown one of 3 possible banks of pictures balanced for phonemic complexity which are randomly assigned to prevent learning effect. Each bank contains 15 items. Each trial is scored by an examiner as accurate (1) or inaccurate (0) based on articulatory accuracy of the participant's response. The average of all trials is calculated for each participant. Total scores range from 0-15 with higher scores indicating better naming accuracy/performance.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Boston Naming Test</measure>
    <time_frame>30 minutes</time_frame>
    <description>The Boston Naming Test contains 60 line drawings of objects ranging from very common objects to less familiar. The examiner scores each item + or - according to scoring procedures. Total scores are calculated by adding up the number correct. Scores range from 0 to 60. Higher scores indicate greater ability to name objects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Western Aphasia Battery Total Score</measure>
    <time_frame>60 minutes</time_frame>
    <description>The Western Aphasia Battery, a standardized assessment of language for individuals with aphasia, contains 32 short tasks. Each task has a separate scoring scheme yielding 8 sub-scores. Total score range from 0-100 with lower scores indicating greater aphasia severity. A score between 0-25 is very severe aphasia, 26-50 is severe aphasia, 51-75 is moderate aphasia, and 76-above is mild aphasia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Working Memory Total Score</measure>
    <time_frame>2 months</time_frame>
    <description>During the Working Memory battery, participants complete 12 auditory only or auditory &amp; visual computer-based recall tasks. Twelve subset scores are calculated. Ten subtest ranges from 0-40 and 2 range from 0-60. Total score is calculated as sum of subtest scores and ranges from 0-520 with higher scores indicating greater working memory.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Aphasia</condition>
  <arm_group>
    <arm_group_label>Prime Condition</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The primed (PRIME) condition is an intervention that will consist of presentation of a-tDCS for 20 minutes to the dorsolateral prefrontal cortex prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-Prime Condition/Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The non-primed (NON-PRIME) condition, or sham controlled, is an intervention that will consist of presentation of sham tDCS to the dorsolateral prefrontal cortex for 20 minutes prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial direct current stimulation</intervention_name>
    <description>Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation tool that presents a low current that induces bi-directional polarity-dependent changes in the cortex to facilitate focal, prolonged shifts in cortical excitability at or around the time stimulation is provided. Anodal tDCS (a-tDCS), in which the positively charged electrode is placed over the targeted cortical region, has been shown to increase cortical excitability (upregulation), similar to long-term potentiation (LTP). Combining a-tDCS with behavioral-based approaches has been suggested to enhance the learning process and increase the likelihood of retention.</description>
    <arm_group_label>Non-Prime Condition/Control</arm_group_label>
    <arm_group_label>Prime Condition</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  completion of high school or GED, normal or corrected-to-normal vision, adequate&#xD;
             hearing acuity for 1:1 conversational exchanges, use of English as primary language, a&#xD;
             vascular lesion in the dominant left hemisphere verified by an MRI scan within six&#xD;
             months of the start of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  no previous history of neurological- or psychiatric-based illnesses or disease,&#xD;
             language or learning disabilities, or alcohol/substance abuse; no history of seizures;&#xD;
             no metal implants in the head (except dental fillings); no lesion in the left DLPFC&#xD;
             confirmed by MRI; no current pregnancy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sharyl A Samargia, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota and University of Wisconsin</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>August 25, 2014</study_first_submitted>
  <study_first_submitted_qc>August 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2014</study_first_posted>
  <results_first_submitted>September 28, 2020</results_first_submitted>
  <results_first_submitted_qc>January 29, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 18, 2021</results_first_posted>
  <last_update_submitted>September 27, 2022</last_update_submitted>
  <last_update_submitted_qc>September 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Broca's Aphasia</keyword>
  <keyword>Transcranial Direct Current Stimulation</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>No</sharing_ipd>
    <ipd_description>The protocol for sharing individual participant data with other researchers has not yet been determined as data collection is in progress.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 4, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT02226796/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Primed tDCS Condition First, Then Non-Prime Condition</title>
          <description>The primed (PRIME) condition is an intervention that will consist of presentation of a-tDCS for 20 minutes to dorsolateral prefrontal cortex prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.&#xD;
The non-primed (NONPRIMED) condition, or sham/control is an intervention that will consist of presentation of sham tDCS for 20 minutes to dorsolateral prefrontal cortex prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.</description>
        </group>
        <group group_id="P2">
          <title>Non-Prime Condition First, Then Primed Condition</title>
          <description>The non-primed (NONPRIMED) condition, or sham/control is an intervention that will consist of presentation of sham tDCS for 20 minutes to dorsolateral prefrontal cortex prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.&#xD;
The primed (PRIME) condition is an intervention that will consist of presentation of a-tDCS for 20 minutes to dorsolateral prefrontal cortex prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>First Intervention Phase (Week 1)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Baseline Assessment</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Follow Up Assessment</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Washout (Weeks 2-5)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Second Intervention Phase (Week 6)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Baseline Assessment</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Follow Up Assessment</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Sham Controlled tDCS Combined With Behavioral Naming Treatment</title>
          <description>The primed (PRIME) condition is an intervention that will consist of presentation of a-tDCS for 20 minutes prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.&#xD;
The non-prime (NONPRIME) condition, sham/control is an intervention that will consist of 40 minutes of naming treatment only, followed by an additional 20 minutes of concurrent naming treatment with a-tDCS.&#xD;
Behavioral measures taken include: working memory, naming reaction time and naming accuracy</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58.33" spread="18.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Working Memory</title>
          <description>During the Working Memory battery, participants completed 12 auditory only or auditory &amp; visual computer-based recall tasks. Twelve subset scores were calculated. Total score is calculated as sum of subtest scores and ranges from 0-520 with higher scores indicating greater working memory.&#xD;
The following auditory and auditory/visual subtests have a possible scoring range between 0-40: phonologically similar and dissimilar word span, word length (short and long) and word span The digit span (auditory and visual/auitory) has scoring range of 0-60. Higher values represent better performance.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>AudioVisual_LongWordLength</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16.33" spread="12.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AudioVisual_ShortWordLength</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17" spread="12.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AudioVisual_WordSpan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18.66" spread="11.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visual_DigitSpan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8.66" spread="3.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visual_PhonologicallySimilarWords</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.66" spread="6.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visual_PhonologicallyDissimilarWords</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12.5" spread="3.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visual_LongWordLength</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6" spread="4.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visual_ShortWordLength</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.66" spread="5.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visual_WordSpan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11" spread="3.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="148" spread="102.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Western Aphasia Battery Score</title>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="52.23" spread="12.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Boston Naming Test</title>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12" spread="0.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Naming Reaction Time</title>
          <description>Participants are shown one or 3 possible banks of pictures balanced for phonemic complexity which are randomly assigned to prevent learning effect. Each bank contains 10* items. Time to recall is measured using a stop watch. The mean time to recall across all items is calculated and reported in milliseconds. The smaller the number, the faster / better the reaction time is.</description>
          <units>time in milliseconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2986.03" spread="1260.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Naming Accuracy</title>
          <description>Participants are shown one or 3 possible banks of pictures balanced for phonemic complexity which are randomly assigned to prevent learning effect. Each bank contains 10* items. Each trial is scored by an examiner as accurate (1) or inaccurate (0). The sum* of all trials is calculated. Total scores range from 0-10* with higher scores indicating better naming accuracy/performance.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.48" spread="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Naming Reaction Time</title>
        <description>Participants are shown one or 3 possible banks of pictures balanced for phonemic complexity which are randomly assigned to prevent learning effect. Each bank contains 15 items. Time to recall is measured using a stop watch. The mean time to recall across all items is calculated and reported in milliseconds. The smaller the number, the faster / better the reaction time is.</description>
        <time_frame>40 minutes</time_frame>
        <population>This is a single subject cross over design where all three participants received both prime and non-prime condition</population>
        <group_list>
          <group group_id="O1">
            <title>Prime Condition</title>
            <description>The primed (PRIME) condition is an intervention that will consist of presentation of a-tDCS for 20 minutes to the dorsolateral prefrontal cortex prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.&#xD;
Transcranial direct current stimulation: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation tool that presents a low current that induces bi-directional polarity-dependent changes in the cortex to facilitate focal, prolonged shifts in cortical excitability at or around the time stimulation is provided. Anodal tDCS (a-tDCS), in which the positively charged electrode is placed over the targeted cortical region, has been shown to increase cortical excitability (upregulation), similar to long-term potentiation (LTP). Combining a-tDCS with behavioral-based approaches has been suggested to enhance the learning process and increase the likelihood of retention.</description>
          </group>
          <group group_id="O2">
            <title>Non-Prime Condition/Control</title>
            <description>The non-primed (NON-PRIME) condition, or sham controlled, is an intervention that will consist of presentation of sham tDCS to the dorsolateral prefrontal cortex for 20 minutes prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.&#xD;
Transcranial direct current stimulation: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation tool that presents a low current that induces bi-directional polarity-dependent changes in the cortex to facilitate focal, prolonged shifts in cortical excitability at or around the time stimulation is provided. Anodal tDCS (a-tDCS), in which the positively charged electrode is placed over the targeted cortical region, has been shown to increase cortical excitability (upregulation), similar to long-term potentiation (LTP). Combining a-tDCS with behavioral-based approaches has been suggested to enhance the learning process and increase the likelihood of retention.</description>
          </group>
        </group_list>
        <measure>
          <title>Naming Reaction Time</title>
          <description>Participants are shown one or 3 possible banks of pictures balanced for phonemic complexity which are randomly assigned to prevent learning effect. Each bank contains 15 items. Time to recall is measured using a stop watch. The mean time to recall across all items is calculated and reported in milliseconds. The smaller the number, the faster / better the reaction time is.</description>
          <population>This is a single subject cross over design where all three participants received both prime and non-prime condition</population>
          <units>milliseconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1829.11" spread="643.40"/>
                    <measurement group_id="O2" value="3345.97" spread="1428.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Naming Accuracy</title>
        <description>Participants are shown one of 3 possible banks of pictures balanced for phonemic complexity which are randomly assigned to prevent learning effect. Each bank contains 15 items. Each trial is scored by an examiner as accurate (1) or inaccurate (0) based on articulatory accuracy of the participant's response. The average of all trials is calculated for each participant. Total scores range from 0-15 with higher scores indicating better naming accuracy/performance.</description>
        <time_frame>40 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Prime Condition</title>
            <description>The primed (PRIME) condition is an intervention that will consist of presentation of a-tDCS for 20 minutes to the dorsolateral prefrontal cortex prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.&#xD;
Transcranial direct current stimulation: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation tool that presents a low current that induces bi-directional polarity-dependent changes in the cortex to facilitate focal, prolonged shifts in cortical excitability at or around the time stimulation is provided. Anodal tDCS (a-tDCS), in which the positively charged electrode is placed over the targeted cortical region, has been shown to increase cortical excitability (upregulation), similar to long-term potentiation (LTP). Combining a-tDCS with behavioral-based approaches has been suggested to enhance the learning process and increase the likelihood of retention.</description>
          </group>
          <group group_id="O2">
            <title>Non-Prime Condition/Control</title>
            <description>The non-primed (NON-PRIME) condition, or sham controlled, is an intervention that will consist of presentation of sham tDCS to the dorsolateral prefrontal cortex for 20 minutes prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.&#xD;
Transcranial direct current stimulation: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation tool that presents a low current that induces bi-directional polarity-dependent changes in the cortex to facilitate focal, prolonged shifts in cortical excitability at or around the time stimulation is provided. Anodal tDCS (a-tDCS), in which the positively charged electrode is placed over the targeted cortical region, has been shown to increase cortical excitability (upregulation), similar to long-term potentiation (LTP). Combining a-tDCS with behavioral-based approaches has been suggested to enhance the learning process and increase the likelihood of retention.</description>
          </group>
        </group_list>
        <measure>
          <title>Naming Accuracy</title>
          <description>Participants are shown one of 3 possible banks of pictures balanced for phonemic complexity which are randomly assigned to prevent learning effect. Each bank contains 15 items. Each trial is scored by an examiner as accurate (1) or inaccurate (0) based on articulatory accuracy of the participant's response. The average of all trials is calculated for each participant. Total scores range from 0-15 with higher scores indicating better naming accuracy/performance.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.95" spread="2.59"/>
                    <measurement group_id="O2" value="6.044" spread="2.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Boston Naming Test</title>
        <description>The Boston Naming Test contains 60 line drawings of objects ranging from very common objects to less familiar. The examiner scores each item + or - according to scoring procedures. Total scores are calculated by adding up the number correct. Scores range from 0 to 60. Higher scores indicate greater ability to name objects.</description>
        <time_frame>30 minutes</time_frame>
        <population>The Co-PI collected data using the Boston Naming Test at baseline (before either prime or non-prime condition) and after both conditions were complete. No BNT data was collected between the two conditions, therefore we cannot determine the impact of the prime condition on BNT scores. Flawed execution of this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prime Condition</title>
            <description>The primed (PRIME) condition is an intervention that will consist of presentation of a-tDCS for 20 minutes to the dorsolateral prefrontal cortex prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.&#xD;
Transcranial direct current stimulation: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation tool that presents a low current that induces bi-directional polarity-dependent changes in the cortex to facilitate focal, prolonged shifts in cortical excitability at or around the time stimulation is provided. Anodal tDCS (a-tDCS), in which the positively charged electrode is placed over the targeted cortical region, has been shown to increase cortical excitability (upregulation), similar to long-term potentiation (LTP). Combining a-tDCS with behavioral-based approaches has been suggested to enhance the learning process and increase the likelihood of retention.</description>
          </group>
          <group group_id="O2">
            <title>Non-Prime Condition/Control</title>
            <description>The non-primed (NON-PRIME) condition, or sham controlled, is an intervention that will consist of presentation of sham tDCS to the dorsolateral prefrontal cortex for 20 minutes prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.&#xD;
Transcranial direct current stimulation: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation tool that presents a low current that induces bi-directional polarity-dependent changes in the cortex to facilitate focal, prolonged shifts in cortical excitability at or around the time stimulation is provided. Anodal tDCS (a-tDCS), in which the positively charged electrode is placed over the targeted cortical region, has been shown to increase cortical excitability (upregulation), similar to long-term potentiation (LTP). Combining a-tDCS with behavioral-based approaches has been suggested to enhance the learning process and increase the likelihood of retention.</description>
          </group>
        </group_list>
        <measure>
          <title>Boston Naming Test</title>
          <description>The Boston Naming Test contains 60 line drawings of objects ranging from very common objects to less familiar. The examiner scores each item + or - according to scoring procedures. Total scores are calculated by adding up the number correct. Scores range from 0 to 60. Higher scores indicate greater ability to name objects.</description>
          <population>The Co-PI collected data using the Boston Naming Test at baseline (before either prime or non-prime condition) and after both conditions were complete. No BNT data was collected between the two conditions, therefore we cannot determine the impact of the prime condition on BNT scores. Flawed execution of this outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Western Aphasia Battery Total Score</title>
        <description>The Western Aphasia Battery, a standardized assessment of language for individuals with aphasia, contains 32 short tasks. Each task has a separate scoring scheme yielding 8 sub-scores. Total score range from 0-100 with lower scores indicating greater aphasia severity. A score between 0-25 is very severe aphasia, 26-50 is severe aphasia, 51-75 is moderate aphasia, and 76-above is mild aphasia.</description>
        <time_frame>60 minutes</time_frame>
        <population>The Co-PI collected data using the Western Aphasia Battery at baseline (before either prime or non-prime condition) and after both conditions were complete. No BNT data was collected between the two conditions, therefore we cannot determine the impact of the prime condition on WAB scores. Flawed execution of this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prime Condition</title>
            <description>The primed (PRIME) condition is an intervention that will consist of presentation of a-tDCS for 20 minutes to the dorsolateral prefrontal cortex prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.&#xD;
Transcranial direct current stimulation: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation tool that presents a low current that induces bi-directional polarity-dependent changes in the cortex to facilitate focal, prolonged shifts in cortical excitability at or around the time stimulation is provided. Anodal tDCS (a-tDCS), in which the positively charged electrode is placed over the targeted cortical region, has been shown to increase cortical excitability (upregulation), similar to long-term potentiation (LTP). Combining a-tDCS with behavioral-based approaches has been suggested to enhance the learning process and increase the likelihood of retention.</description>
          </group>
          <group group_id="O2">
            <title>Non-Prime Condition/Control</title>
            <description>The non-primed (NON-PRIME) condition, or sham controlled, is an intervention that will consist of presentation of sham tDCS to the dorsolateral prefrontal cortex for 20 minutes prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.&#xD;
Transcranial direct current stimulation: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation tool that presents a low current that induces bi-directional polarity-dependent changes in the cortex to facilitate focal, prolonged shifts in cortical excitability at or around the time stimulation is provided. Anodal tDCS (a-tDCS), in which the positively charged electrode is placed over the targeted cortical region, has been shown to increase cortical excitability (upregulation), similar to long-term potentiation (LTP). Combining a-tDCS with behavioral-based approaches has been suggested to enhance the learning process and increase the likelihood of retention.</description>
          </group>
        </group_list>
        <measure>
          <title>Western Aphasia Battery Total Score</title>
          <description>The Western Aphasia Battery, a standardized assessment of language for individuals with aphasia, contains 32 short tasks. Each task has a separate scoring scheme yielding 8 sub-scores. Total score range from 0-100 with lower scores indicating greater aphasia severity. A score between 0-25 is very severe aphasia, 26-50 is severe aphasia, 51-75 is moderate aphasia, and 76-above is mild aphasia.</description>
          <population>The Co-PI collected data using the Western Aphasia Battery at baseline (before either prime or non-prime condition) and after both conditions were complete. No BNT data was collected between the two conditions, therefore we cannot determine the impact of the prime condition on WAB scores. Flawed execution of this outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Working Memory Total Score</title>
        <description>During the Working Memory battery, participants complete 12 auditory only or auditory &amp; visual computer-based recall tasks. Twelve subset scores are calculated. Ten subtest ranges from 0-40 and 2 range from 0-60. Total score is calculated as sum of subtest scores and ranges from 0-520 with higher scores indicating greater working memory.</description>
        <time_frame>2 months</time_frame>
        <population>The Co-PI collected data using the working memory assessment at baseline (before either prime or non-prime condition) and after both conditions were complete. No BNT data was collected between the two conditions, therefore we cannot determine the impact of the prime condition on working memory scores. Flawed execution of this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Prime Condition</title>
            <description>The primed (PRIME) condition is an intervention that will consist of presentation of a-tDCS for 20 minutes to the dorsolateral prefrontal cortex prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.&#xD;
Transcranial direct current stimulation: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation tool that presents a low current that induces bi-directional polarity-dependent changes in the cortex to facilitate focal, prolonged shifts in cortical excitability at or around the time stimulation is provided. Anodal tDCS (a-tDCS), in which the positively charged electrode is placed over the targeted cortical region, has been shown to increase cortical excitability (upregulation), similar to long-term potentiation (LTP). Combining a-tDCS with behavioral-based approaches has been suggested to enhance the learning process and increase the likelihood of retention.</description>
          </group>
          <group group_id="O2">
            <title>Non-Prime Condition/Control</title>
            <description>The non-primed (NON-PRIME) condition, or sham controlled, is an intervention that will consist of presentation of sham tDCS to the dorsolateral prefrontal cortex for 20 minutes prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.&#xD;
Transcranial direct current stimulation: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation tool that presents a low current that induces bi-directional polarity-dependent changes in the cortex to facilitate focal, prolonged shifts in cortical excitability at or around the time stimulation is provided. Anodal tDCS (a-tDCS), in which the positively charged electrode is placed over the targeted cortical region, has been shown to increase cortical excitability (upregulation), similar to long-term potentiation (LTP). Combining a-tDCS with behavioral-based approaches has been suggested to enhance the learning process and increase the likelihood of retention.</description>
          </group>
        </group_list>
        <measure>
          <title>Working Memory Total Score</title>
          <description>During the Working Memory battery, participants complete 12 auditory only or auditory &amp; visual computer-based recall tasks. Twelve subset scores are calculated. Ten subtest ranges from 0-40 and 2 range from 0-60. Total score is calculated as sum of subtest scores and ranges from 0-520 with higher scores indicating greater working memory.</description>
          <population>The Co-PI collected data using the working memory assessment at baseline (before either prime or non-prime condition) and after both conditions were complete. No BNT data was collected between the two conditions, therefore we cannot determine the impact of the prime condition on working memory scores. Flawed execution of this outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 months</time_frame>
      <desc>Each participant was asked if they experienced headache or itchy/tingly sensation at site of stimulation during and/or after tDCS sessions.</desc>
      <group_list>
        <group group_id="E1">
          <title>Primed tDCS Condition</title>
          <description>The primed (PRIME) condition is an intervention that will consist of presentation of a-tDCS for 20 minutes to dorsolateral prefrontal cortex prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair. Naming reaction time and accuracy will be measured as well as working memory.</description>
        </group>
        <group group_id="E2">
          <title>Non-Prime Condition</title>
          <description>The non-primed (NONPRIMED) condition, or sham/control is an intervention that will consist of presentation of sham tDCS for 20 minutes to dorsolateral prefrontal cortex prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair. Naming reaction time and accuracy will be measured as well as working memory.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Sharyl Samargia-Grivette</name_or_title>
      <organization>University of Minnesota Duluth</organization>
      <phone>218-726-8347</phone>
      <email>samargia@d.umn.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02226796
org study id: 1506M73043
nct id: NCT02226796
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
We hypothesize patients who have difficulty with word recall (naming pictures) due to a
      stroke will experience greater benefit in word recall after receiving a combination of
      transcranial direct current stimulation (tDCS) and traditional behavioral treatment. This
      study will investigate the effects of the timing of tDCS in relationship to the behavioral
      treatment to determine the most optimal protocol. Transcranial direct current stimulation
      involves placing two electrodes on your scalp and sending a very small electrical current to
      excite the brain cells of the target site.
Specific Aims Aim 1: Identify and quantify the effects of a-tDCS to the left dorsolateral
      prefrontal cortex (DLPFC) in conjunction with intensive behavioral treatment on naming in
      non-fluent aphasia. a-tDCS (2mA for 20 minutes) will be applied over the left DLPFC with
      cathode over the right orbit. Pre and post treatment behavioral measures of naming and
      working memory will be used to quantify and compare differences. Hypothesis 1: a-tDCS will
      result in improvements in naming accuracy, naming response times, and working memory (WM) in
      participants with non-fluent aphasia.

      Aim 2: Compare the effects of a-tDCS applied to the left DLPFC before behavioral treatment to
      during behavioral treatment in non-fluent aphasia. a-tDCS (2mA for 20 minutes) will be
      applied over the left DLPFC with cathode over the right orbit. Pre and post treatment
      behavioral measures of naming and working memory will be used to quantify and compare
      functional differences between conditions. Hypothesis 1: a-tDCS to the DLPFC during treatment
      will result in a greater improvement of naming accuracy, naming response time and WM in
      participants with non-fluent aphasia.

      Significance The findings from the proposed study will lay the foundation for a larger
      clinical trial which will in turn have a significant impact on individuals with aphasia given
      that naming deficits are a common symptom in this population. As the presence of naming
      deficits has a negative relationship to emotional well-being and functional communication
      26-30, treatment that improves naming deficits will positively influence quality of life in
      many of these individuals. The approach taken to remediate naming deficits in aphasia is to
      treat impaired WM systems on the premise that certain cognitive processes underlie linguistic
      functions in aphasia. This approach represents a departure from most behavioral-based naming
      treatment approach, but reflects a growing recognition that WM systems in individuals with
      aphasia impact their linguistic performance 5, 31. The addition of a-tDCS as a
      neuromodulation tool to increase cortical excitability (upregulate) the working memory center
      to target naming is a novel approach. In addition, this study will further elucidate the
      optimal timing of a-tDCS in order to achieve the most beneficial outcomes, which have not yet
      been reported. These findings, along with other related studies, will shape future clinical
      practice guidelines as more studies adopt a concurrent cognitive-linguistic approach to treat
      linguistic deficits in aphasia.

      Design & Methodology Participants. Four individuals with aphasia will be recruited. These
      participants must meet the following inclusionary/exclusionary criteria: a) completion of
      high school or GED; b) normal or corrected-to-normal vision; c) adequate hearing acuity for
      1:1 conversational exchanges; d) use of English as primary language; e) a vascular lesion in
      the dominant left hemisphere verified by an MRI scan within six months of the start of the
      study. These participants must also meet the following exclusionary criteria: a) no previous
      history of neurological- or psychiatric-based illnesses or disease, language or learning
      disabilities, or alcohol/substance abuse; b) no history of seizures; c) no metal implants in
      the head (except dental fillings); d) no lesion in the left DLPFC confirmed by MRI; e) no
      current pregnancy. Pre-Test Behavioral Measures. Participants will be seen between 2-3
      sessions to undergo comprehensive cognitive-linguistic testing prior to initiation of
      treatment. Testing will take place at the University of Minnesota (UMN) Clinical
      Translational Science Institute (CTSI). Behavioral test measures will include the WAB 32 in
      order to obtain the WAB Aphasia Quotient (WAB AQ), Boston Naming Test (BNT) 33 and the
      Apraxia Battery for Adults (ABA-2) 34. The WAB AQ will provide a general classification of
      aphasia subtype, scores from the BNT will provide the level of severity of naming impairment,
      and ABA-2 performance will be used to assess severity of apraxia of speech (AoS). To assess
      the integrity of the phonological store, participants will be tested for the effects of
      phonological similarity using both auditory and visual presentation 35, 36. To assess the
      integrity of subvocal rehearsal processes, participants will be tested for the effects of
      word length on both auditory and visual span 37; the effects of articulatory suppression on
      recall performance 37, 38; and rhyme judgments 39-41. Protocols that have been adapted for
      individuals with aphasia will be followed42-45. These tests will be used to distinguish
      behavioral evidence of deficient subvocal rehearsal processes from deficient phonological
      short-term store. Individuals with a range of moderate to moderately severe nonfluent
      aphasia, a range of moderate to moderately severe anomia, and a range of mild to no AoS will
      be chosen for the study. Baseline probes will also be obtained prior to the initiation of the
      study. Stability of baseline performance, defined as no more than 20% difference between
      scores,will be obtained over three consecutive sessions in order to establish experimental
      control. Post-Test Behavioral Measures. Participants will also be seen for post-treatment
      testing following the implementation of the treatment protocol. Testing will take place in
      the participant's home. Post-treatment behavioral measures will include BNT, the ABA-2, WM
      tasks, and naming treatment and control items. It is anticipated that only one session will
      be needed for post-treatment testing. An adverse events survey will also be provided to
      assess the participant's level of discomfort during use of tDCS. tDCS Protocol. Each
      participant will be seated comfortably in a chair. A swim cap will be placed on the
      participant's head to identify cranial landmarks for accurate electrode placement. The area
      referred to as F3 by the International 10/20 system for electroencephalogram electrode
      placement46 has been established as the optimal location for targeting the left DLPFC25,
      47-49. The F3 region will be located by marking the vertex (the midpoint between left and
      right tragus and midpoint between nasion and inion), measuring the head circumference. When
      these measurements are entered into the Beam F3 Locator Software50, additional values are
      provided to reliably identify the location of F3. Once F3 has been established, two saline
      soaked surface sponge electrodes (352cm) will be prepared and placed. For optimal anodal
      stimulation to the DLPFC, the anode will be placed over F3 and the cathode will be placed
      over the right supraorbital region23, 24, 47, 48. A current of 2mA will be delivered for 20
      minutes 24 by a multichannel transcranial current stimulator (Starstim, Neuroelectrics
      Corporation; Cambridge, MA). a-tDCS will be applied before and during behavioral treatment in
      the design specified below.

      Treatment Design. Two treatment conditions will be presented in a counter-balanced order in a
      cross-over design. The non-prime (NONPRIME) condition will consist of 40 minutes of naming
      treatment only, followed by an additional 20 minutes of concurrent naming treatment with
      a-tDCS. The primed (PRIME) condition will consist of presentation of a-tDCS for 20 minutes
      prior to naming treatment, while the subject sits quietly and comfortably in a chair. After
      the 20-minute priming period, the a-tDCS will be removed and the participant will receive
      naming treatment for 60 minutes. Both conditions will be presented over four consecutive
      days. Two participants will receive NON-PRIME-PRIME sequence, with a one-month washout period
      between the two conditions. Two other participants will receive PRIME-NON-PRIME sequence,
      with a one-month washout period between the two conditions. Naming reaction time will be
      immediately evaluated after each treatment day.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Naming Reaction Time
time frame: 40 minutes
description: Participants are shown one or 3 possible banks of pictures balanced for phonemic complexity which are randomly assigned to prevent learning effect. Each bank contains 15 items. Time to recall is measured using a stop watch. The mean time to recall across all items is calculated and reported in milliseconds. The smaller the number, the faster / better the reaction time is.
measure: Naming Accuracy
time frame: 40 minutes
description: Participants are shown one of 3 possible banks of pictures balanced for phonemic complexity which are randomly assigned to prevent learning effect. Each bank contains 15 items. Each trial is scored by an examiner as accurate (1) or inaccurate (0) based on articulatory accuracy of the participant's response. The average of all trials is calculated for each participant. Total scores range from 0-15 with higher scores indicating better naming accuracy/performance.
measure: Boston Naming Test
time frame: 30 minutes
description: The Boston Naming Test contains 60 line drawings of objects ranging from very common objects to less familiar. The examiner scores each item + or - according to scoring procedures. Total scores are calculated by adding up the number correct. Scores range from 0 to 60. Higher scores indicate greater ability to name objects.
measure: Western Aphasia Battery Total Score
time frame: 60 minutes
description: The Western Aphasia Battery, a standardized assessment of language for individuals with aphasia, contains 32 short tasks. Each task has a separate scoring scheme yielding 8 sub-scores. Total score range from 0-100 with lower scores indicating greater aphasia severity. A score between 0-25 is very severe aphasia, 26-50 is severe aphasia, 51-75 is moderate aphasia, and 76-above is mild aphasia.
measure: Working Memory Total Score
time frame: 2 months
description: During the Working Memory battery, participants complete 12 auditory only or auditory & visual computer-based recall tasks. Twelve subset scores are calculated. Ten subtest ranges from 0-40 and 2 range from 0-60. Total score is calculated as sum of subtest scores and ranges from 0-520 with higher scores indicating greater working memory.
arm group label: Prime Condition
arm group type: Active Comparator
description: The primed (PRIME) condition is an intervention that will consist of presentation of a-tDCS for 20 minutes to the dorsolateral prefrontal cortex prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.
arm group label: Non-Prime Condition/Control
arm group type: Active Comparator
description: The non-primed (NON-PRIME) condition, or sham controlled, is an intervention that will consist of presentation of sham tDCS to the dorsolateral prefrontal cortex for 20 minutes prior to 40 minutes of behavioral naming treatment, while the subject sits comfortably in a chair.
intervention type: Device
intervention name: Transcranial direct current stimulation
description: Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation tool that presents a low current that induces bi-directional polarity-dependent changes in the cortex to facilitate focal, prolonged shifts in cortical excitability at or around the time stimulation is provided. Anodal tDCS (a-tDCS), in which the positively charged electrode is placed over the targeted cortical region, has been shown to increase cortical excitability (upregulation), similar to long-term potentiation (LTP). Combining a-tDCS with behavioral-based approaches has been suggested to enhance the learning process and increase the likelihood of retention.
arm group label: Non-Prime Condition/Control
arm group label: Prime Condition
criteria: 
gender: All
minimum age: 20 Years
maximum age: 85 Years
healthy volunteers: No
last name: Sharyl A Samargia, PhD
role: Principal Investigator
affiliation: University of Minnesota and University of Wisconsin
facility: 
country: United States
responsible party type: Sponsor
mesh term: Aphasia
sharing ipd: No
ipd description: The protocol for sharing individual participant data with other researchers has not yet been determined as data collection is in progress.
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 