xml: <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/NCT05978804</url>
    </required_header>
    <id_info>
      <org_study_id>NA_00071337-4</org_study_id>
      <nct_id>NCT05978804</nct_id>
    </id_info>
    <brief_title>Home-based tDCS in Frontotemporal Dementia or Alzheimer's Disease</brief_title>
    <official_title>Remote Home-based Electrical Stimulation (tDCS) in Primary Progressive Aphasia (With Frontotemporal Dementia or Alzheimer's Pathology) and Mild Cognitive Impairment/Alzheimer's.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Johns Hopkins University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Johns Hopkins University</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>Yes</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The primary objective of this research is to evaluate the effects of non-invasive brain&#xD;
        stimulation and computerized cognitive training on executive functioning in individuals with&#xD;
        Primary Progressive Aphasia (PPA), mild cognitive impairment (MCI), or dementia. In this&#xD;
        study, investigators will use transcranial direct current stimulation (tDCS) to stimulate the&#xD;
        left dorsolateral prefrontal cortex (DLPFC). Previous studies have demonstrated that tDCS&#xD;
        over the DLPFC led to improvements in attention deficit caused by stroke, Parkinson's&#xD;
        Disease, and major depression as well as language deficits caused by neurodegenerative&#xD;
        conditions such as primary progressive aphasia or mild cognitive impairment. The&#xD;
        investigators seek to expand on this literature by investigating how anodal tDCS paired with&#xD;
        and without cognitive training will impact executive functioning in PPA with Frontotemporal&#xD;
        Dementia or Alzheimer's Disease pathology and Mild Cognitive Impairment/Alzheimer's Disease&#xD;
        (e.g. shifting, updating, monitoring, and manipulation).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        In this within-subject cross-over protocol, all participants will receive both, cognitive&#xD;
        training and brain stimulation tDCS. Participants will be randomly assigned to begin with&#xD;
        either cognitive training and brain stimulation (dual therapy) or just brain stimulation&#xD;
        (monotherapy) and will receive the complementary therapy program in the second round of&#xD;
        treatment. During each period of therapy, participants will receive 50 treatment sessions&#xD;
        over the course of approximately 10 weeks. The computerized cognitive training and brain&#xD;
        stimulation will both be preprogrammed to be done at home by the participant.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 10, 2023</start_date>
    <completion_date type="Anticipated">August 10, 2025</completion_date>
    <primary_completion_date type="Anticipated">August 10, 2025</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>
      <intervention_model_description>Subjects meeting eligibility criteria will be randomized to receive either tDCS + cognitive training or only tDCS. After 50 treatment sessions (approximately 10 weeks) participants will switch to the other condition.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in language composite outcome</measure>
      <time_frame>Before intervention, immediately after intervention</time_frame>
      <description>A single language composite outcome will be generated by computing the mean of the z-scores the following oral and written naming, spelling, and sentence comprehension and repetition tasks: Philadelphia Naming Test (Short Form), Boston Naming Test, Hopkins Action Naming Assessment, Hopkins Dysgraphia Battery, National Alzheimer's Coordinating Center Sentence Repetition. The investigators will take the z-score for each task and aggregate them in order to get a composite z-score.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Executive Composite Outcome</measure>
      <time_frame>Before intervention, immediately after intervention</time_frame>
      <description>A single executive composite will be generated by computing the mean of the z-scores of the tasks below reflecting new learning and memory, processing speed and executive functioning, attention and working memory, and verbal fluency respectively: Rey Auditory Verbal Learning Test, Trail Making Test A and B, Attention Network Task, Digit and Spatial Span, and Category fluency and Verbal Fluency. The investigators will take the z-score for each task and aggregate them in order to get a composite z-score.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Global Cognitive Scores</measure>
      <time_frame>Before intervention, immediately after intervention</time_frame>
      <description>This will be measured using the Montreal Cognitive Assessment (MoCA). Scored out of 30 points, higher is better.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in Selective attention and cognitive flexibility</measure>
      <time_frame>Before intervention, immediately after intervention</time_frame>
      <description>This will be measured using the Attention Network Task (ANT). An efficiency score for executive attention is derived by comparing scores on trials with congruent flankers to trials with incongruent flankers. Subjects will tend to be slower and less accurate for incongruent trials, the size of the different indicates the extent to which an individual can supress conflicting response tendencies. A larger difference between congruent and incongruent trials score indicates a lower executive efficiency.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in attention and task switching</measure>
      <time_frame>Before intervention, immediately after intervention</time_frame>
      <description>This will be measured using Trail Making Task and N-Back (2-back) scores. The Trail Making Test is scored by time. Less time needed to complete the task is indicative of better task-switching. The N-back task is a well-established task that assesses working memory and working memory capacity. Participants are presented with words in sequence and instructed to reply whether the current word matches the one presented 2 words ago. Scoring will be based on the total number of correct responses (hit rate) minus the number of incorrect responses (false alarm rate), where a greater score is better.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in working memory capacity.</measure>
      <time_frame>Before intervention, immediately after intervention</time_frame>
      <description>This will be measured using Digit Span Backward for verbal working memory and spatial span Backward for spatial working memory. The digit span backward is a well-established task that assesses rote immediate verbal memory and working memory. Participants are presented with a series of digits and are instructed to repeat the digits in the reverse order. The spatial span task is an analog to the Digit Span Task, but instead the participants are presented with an array of squares which are sequentially presented and must be touched in the same order. For both tasks scoring is based on the number of digits or blocks shown in a trial (i.e. 1,7 is 2 digits). There are two trials for each span, if both trials are correct the score is a whole number (i.e. 2). If one trial is incorrect in a span, subtract 0.5 from that tier (i.e. 1.5). Increase in score from before to after intervention is considered a benefit.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in level of Depressive Symptoms</measure>
      <time_frame>Before intervention, immediately after intervention</time_frame>
      <description>Measured by the Hamilton Depression Rating Scale (HAM-D) which is a 17-item measure that was designed to assess frequency and intensity of depressive symptoms in patients with Major Depressive Disorder (MDD). This measure contains somatic and suicidal ideation items and has demonstrated reliability, validity, and efficiency in adult populations. Scoring is out of 53, a score of 0-7 is accepted to be normal, a score of 20 or higher indicates at least moderate severity.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">50</enrollment>
    <condition>Mild Cognitive Impairment</condition>
    <condition>Primary Progressive Aphasia</condition>
    <condition>Dementia</condition>
    <arm_group>
      <arm_group_label>Active tDCS on the DLPFC + Cognitive Intervention(s)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive active tDCS on DLPFC + Cognitive Intervention(s) first and then receive only active tDCS Intervention after a three-month washout period.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Active tDCS on the DLPFC only</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive active tDCS on the DLPFC-only intervention first and then receive active tDCS + Cognitive Intervention(s) after a three-month washout period.</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Computerized Cognitive Training via BrainHQ</intervention_name>
      <description>Computerized Cognitive training (BrainHQ)</description>
      <arm_group_label>Active tDCS on the DLPFC + Cognitive Intervention(s)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Active tDCS (tDCS) on DLPFC</intervention_name>
      <description>Device: Active tDCS on DLPFC Stimulation will be delivered by a constant current stimulator (Mind STIM). The electrical current will be administered to a pre-specified region of the brain (DLPFC). The stimulation will be delivered at an intensity of 2 milliamperes (mA) (estimated current density 0.04 mA/cm2; estimated total charge 0.048 Coulombs/cm2) in a ramp-like fashion for a maximum of 20 minutes.</description>
      <arm_group_label>Active tDCS on the DLPFC + Cognitive Intervention(s)</arm_group_label>
      <arm_group_label>Active tDCS on the DLPFC only</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Must be clinically diagnosed with PPA, FTD, MCI or mild AD. Diagnosis will be based on&#xD;
               neuropsychological testing, language testing (most commonly the Western Aphasia&#xD;
               Battery), MRI, and clinical assessment.&#xD;
  &#xD;
            -  Must be right-handed.&#xD;
  &#xD;
            -  Must be proficient in English.&#xD;
  &#xD;
            -  Must have a minimum high-school education.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Uncorrected visual or hearing impairment by self-report.&#xD;
  &#xD;
            -  Stroke/other premorbid neurological disorder affecting the brain.&#xD;
  &#xD;
            -  Any other developmental language-based learning disorder other than PPA.&#xD;
  &#xD;
            -  Inability to follow directions for baseline tasks.&#xD;
  &#xD;
            -  Pre-existing psychiatric disorders such as behavioral disturbances, severe depression,&#xD;
               and schizophrenia that do not allow them to comply or follow the study schedule and&#xD;
               requirements such as repeated evaluation and therapy will be excluded.&#xD;
  &#xD;
          Exclusion Criteria for MRI participation:&#xD;
  &#xD;
            -  Severe claustrophobia.&#xD;
  &#xD;
            -  Cardiac pacemakers or ferromagnetic implants.&#xD;
  &#xD;
            -  Pregnant women.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>50 Years</minimum_age>
      <maximum_age>90 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Kyrana Tsapkini, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Johns Hopkins University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Kyrana Tsapkini, PhD.</last_name>
      <phone>410-736-2940</phone>
      <email>tsapkini@jhmi.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Jessica &quot;Jessie&quot; Gallegos</last_name>
      <email>jgalleg6@jhu.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Johns Hopkins University</name>
        <address>
          <city>Baltimore</city>
          <state>Maryland</state>
          <zip>21287</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Jessica Gallegos, BA</last_name>
        <email>jgalleg6@jhu.edu</email>
      </contact>
      <contact_backup>
        <last_name>Sophia Norvilas, BA</last_name>
        <email>norvilas@jhmi.edu</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 11, 2023</study_first_submitted>
    <study_first_submitted_qc>July 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Dementia</mesh_term>
      <mesh_term>Aphasia</mesh_term>
      <mesh_term>Frontotemporal Dementia</mesh_term>
      <mesh_term>Aphasia, Primary Progressive</mesh_term>
      <mesh_term>Pick Disease of the Brain</mesh_term>
      <mesh_term>Cognitive Dysfunction</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05978804
  org study id: NA_00071337-4
  nct id: NCT05978804
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: Yes
  The primary objective of this research is to evaluate the effects of non-invasive brain
        stimulation and computerized cognitive training on executive functioning in individuals with
        Primary Progressive Aphasia (PPA), mild cognitive impairment (MCI), or dementia. In this
        study, investigators will use transcranial direct current stimulation (tDCS) to stimulate the
        left dorsolateral prefrontal cortex (DLPFC). Previous studies have demonstrated that tDCS
        over the DLPFC led to improvements in attention deficit caused by stroke, Parkinson's
        Disease, and major depression as well as language deficits caused by neurodegenerative
        conditions such as primary progressive aphasia or mild cognitive impairment. The
        investigators seek to expand on this literature by investigating how anodal tDCS paired with
        and without cognitive training will impact executive functioning in PPA with Frontotemporal
        Dementia or Alzheimer's Disease pathology and Mild Cognitive Impairment/Alzheimer's Disease
        (e.g. shifting, updating, monitoring, and manipulation).
  In this within-subject cross-over protocol, all participants will receive both, cognitive
        training and brain stimulation tDCS. Participants will be randomly assigned to begin with
        either cognitive training and brain stimulation (dual therapy) or just brain stimulation
        (monotherapy) and will receive the complementary therapy program in the second round of
        treatment. During each period of therapy, participants will receive 50 treatment sessions
        over the course of approximately 10 weeks. The computerized cognitive training and brain
        stimulation will both be preprogrammed to be done at home by the participant.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: Subjects meeting eligibility criteria will be randomized to receive either tDCS + cognitive training or only tDCS. After 50 treatment sessions (approximately 10 weeks) participants will switch to the other condition.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Change in language composite outcome
  time frame: Before intervention, immediately after intervention
  description: A single language composite outcome will be generated by computing the mean of the z-scores the following oral and written naming, spelling, and sentence comprehension and repetition tasks: Philadelphia Naming Test (Short Form), Boston Naming Test, Hopkins Action Naming Assessment, Hopkins Dysgraphia Battery, National Alzheimer's Coordinating Center Sentence Repetition. The investigators will take the z-score for each task and aggregate them in order to get a composite z-score.
  measure: Change in Executive Composite Outcome
  time frame: Before intervention, immediately after intervention
  description: A single executive composite will be generated by computing the mean of the z-scores of the tasks below reflecting new learning and memory, processing speed and executive functioning, attention and working memory, and verbal fluency respectively: Rey Auditory Verbal Learning Test, Trail Making Test A and B, Attention Network Task, Digit and Spatial Span, and Category fluency and Verbal Fluency. The investigators will take the z-score for each task and aggregate them in order to get a composite z-score.
  measure: Change in Global Cognitive Scores
  time frame: Before intervention, immediately after intervention
  description: This will be measured using the Montreal Cognitive Assessment (MoCA). Scored out of 30 points, higher is better.
  measure: Change in Selective attention and cognitive flexibility
  time frame: Before intervention, immediately after intervention
  description: This will be measured using the Attention Network Task (ANT). An efficiency score for executive attention is derived by comparing scores on trials with congruent flankers to trials with incongruent flankers. Subjects will tend to be slower and less accurate for incongruent trials, the size of the different indicates the extent to which an individual can supress conflicting response tendencies. A larger difference between congruent and incongruent trials score indicates a lower executive efficiency.
  measure: Change in attention and task switching
  time frame: Before intervention, immediately after intervention
  description: This will be measured using Trail Making Task and N-Back (2-back) scores. The Trail Making Test is scored by time. Less time needed to complete the task is indicative of better task-switching. The N-back task is a well-established task that assesses working memory and working memory capacity. Participants are presented with words in sequence and instructed to reply whether the current word matches the one presented 2 words ago. Scoring will be based on the total number of correct responses (hit rate) minus the number of incorrect responses (false alarm rate), where a greater score is better.
  measure: Change in working memory capacity.
  time frame: Before intervention, immediately after intervention
  description: This will be measured using Digit Span Backward for verbal working memory and spatial span Backward for spatial working memory. The digit span backward is a well-established task that assesses rote immediate verbal memory and working memory. Participants are presented with a series of digits and are instructed to repeat the digits in the reverse order. The spatial span task is an analog to the Digit Span Task, but instead the participants are presented with an array of squares which are sequentially presented and must be touched in the same order. For both tasks scoring is based on the number of digits or blocks shown in a trial (i.e. 1,7 is 2 digits). There are two trials for each span, if both trials are correct the score is a whole number (i.e. 2). If one trial is incorrect in a span, subtract 0.5 from that tier (i.e. 1.5). Increase in score from before to after intervention is considered a benefit.
  measure: Change in level of Depressive Symptoms
  time frame: Before intervention, immediately after intervention
  description: Measured by the Hamilton Depression Rating Scale (HAM-D) which is a 17-item measure that was designed to assess frequency and intensity of depressive symptoms in patients with Major Depressive Disorder (MDD). This measure contains somatic and suicidal ideation items and has demonstrated reliability, validity, and efficiency in adult populations. Scoring is out of 53, a score of 0-7 is accepted to be normal, a score of 20 or higher indicates at least moderate severity.
  arm group label: Active tDCS on the DLPFC + Cognitive Intervention(s)
  arm group type: Experimental
  description: Participants will receive active tDCS on DLPFC + Cognitive Intervention(s) first and then receive only active tDCS Intervention after a three-month washout period.
  arm group label: Active tDCS on the DLPFC only
  arm group type: Experimental
  description: Participants will receive active tDCS on the DLPFC-only intervention first and then receive active tDCS + Cognitive Intervention(s) after a three-month washout period.
  intervention type: Other
  intervention name: Computerized Cognitive Training via BrainHQ
  description: Computerized Cognitive training (BrainHQ)
  arm group label: Active tDCS on the DLPFC + Cognitive Intervention(s)
  intervention type: Device
  intervention name: Active tDCS (tDCS) on DLPFC
  description: Device: Active tDCS on DLPFC Stimulation will be delivered by a constant current stimulator (Mind STIM). The electrical current will be administered to a pre-specified region of the brain (DLPFC). The stimulation will be delivered at an intensity of 2 milliamperes (mA) (estimated current density 0.04 mA/cm2; estimated total charge 0.048 Coulombs/cm2) in a ramp-like fashion for a maximum of 20 minutes.
  arm group label: Active tDCS on the DLPFC + Cognitive Intervention(s)
  arm group label: Active tDCS on the DLPFC only
  criteria: 
  gender: All
  minimum age: 50 Years
  maximum age: 90 Years
  healthy volunteers: No
  last name: Kyrana Tsapkini, PhD
  role: Principal Investigator
  affiliation: Johns Hopkins University
  last name: Kyrana Tsapkini, PhD.
  phone: 410-736-2940
  email: tsapkini@jhmi.edu
  last name: Jessica "Jessie" Gallegos
  email: jgalleg6@jhu.edu
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: United States
  responsible party type: Sponsor
  mesh term: Dementia
  mesh term: Aphasia
  mesh term: Frontotemporal Dementia
  mesh term: Aphasia, Primary Progressive
  mesh term: Pick Disease of the Brain
  mesh term: Cognitive Dysfunction