<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/NCT04404153</url>
  </required_header>
  <id_info>
    <org_study_id>2020-11274</org_study_id>
    <nct_id>NCT04404153</nct_id>
  </id_info>
  <brief_title>NeurostImulation for Cognitive Enhancement in Alzheimer's Disease</brief_title>
  <acronym>NICE-AD</acronym>
  <official_title>Non-Invasive Home Neurostimulation for Mild to Moderate Alzheimer's Disease: Double-Blind, Sham Controlled Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Albert Einstein College of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>MJHS Institute for Innovation in Palliative Care</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Albert Einstein College of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The prevalence of Alzheimer's Disease (AD) is rising, but existing medications provide only&#xD;
      modest control of cognitive decline and associated symptoms, and novel therapies are urgently&#xD;
      needed. This randomized sham-controlled trial will determine if an innovative low-risk&#xD;
      remotely-supervised transcranial Direct Current Stimulation (tDCS) applied over the area of&#xD;
      the dorsolateral prefrontal cortex for 30 minutes at the intensity of 2 mA five times per&#xD;
      week for 6 months at home can improve cognitive performance and symptoms and modulate&#xD;
      neuroimaging markers of neuroplasticity in 100 patients with mild to moderate AD. If&#xD;
      effective, this novel intervention can substantially enhance AD symptom management at home,&#xD;
      improve quality of life of AD patients and their families, and reduce burden associated with&#xD;
      this debilitating illness.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The hallmark of Alzheimer's Disease (AD) is cognitive decline with varied associated symptoms&#xD;
      and signs. Unfortunately, there is no cure as yet for AD. Available treatments, including 5&#xD;
      FDA-approved medications, have limited efficacy in terms of slowing pathological progression&#xD;
      or controlling the symptoms and signs of cognitive decline in AD patients. Given the high&#xD;
      burdens and costs of AD, and the therapeutic limitations, the development of novel treatment&#xD;
      approaches for AD is of the highest importance for patients, families, medical providers, and&#xD;
      society. This randomized controlled trial will determine if innovative, low-risk&#xD;
      neurostimulation at home for 6 months can improve cognitive performance and symptoms in&#xD;
      patients with mild to moderate AD.&#xD;
&#xD;
      The primary objective is to determine the effects produced by 6 months of active tDCS or sham&#xD;
      delivered over dorsolateral prefrontal cortex (DLPFC) in home settings on global cognitive&#xD;
      performance (assessed by ADAS-Cog test - primary outcome), and secondarily on executive&#xD;
      control/spatial selective attention (Eriksen Flanker Test), depressed mood (Geriatric&#xD;
      depression scale), quality of life (Quality of Life Questionnaire-Alzheimer's Disease), and&#xD;
      patient satisfaction with both the device and procedure (Neurostimulation User's Survey), in&#xD;
      mild-to-moderate AD patients (n=100). The investigators also aim to determine functional and&#xD;
      structural brain connectivity/network changes in response to the study intervention using&#xD;
      functional Magnetic Resonance Imaging (fMRI; during rest and during executive function&#xD;
      tasks), diffusion-weighted imaging (DWI), and multivariate covariance-based analytic&#xD;
      approaches. Lastly, the investigators aim to examine time characteristics (durability) of the&#xD;
      tDCS behavioral and neuroplasticity effects for up to 3 months following the intervention&#xD;
      period.&#xD;
&#xD;
      The intervention will consist of remotely supervised active tDCS stimulation and sham tDCS&#xD;
      stimulation over the area of the dorsolateral prefrontal cortex, applied at home for 30&#xD;
      minutes 5 times per week for 6 months. Participants randomized to the active tDCS will&#xD;
      receive at each application 30 minutes of direct current stimulation at the intensity of 2&#xD;
      mA. Participants randomized to the sham group will receive sham tDCS which consists of&#xD;
      current ramped up to 2mA over 30 seconds, ramped down over 30 seconds and stay at 0 current&#xD;
      for the remaining time of the 30-minute application.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 25, 2021</start_date>
  <completion_date type="Anticipated">January 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Global Cognitive Performance</measure>
    <time_frame>Baseline, at 6 months (immediately after the 6-month intervention)</time_frame>
    <description>Change in The Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) was developed as an outcome measure for dementia interventions; its primary purpose was to be an index of global cognition in response to therapies. It assesses multiple cognitive domains across 11 items: Word Recall Task, Naming Objects and Fingers, Following Commands, Constructional Praxis, Ideational Praxis, Orientation, Word Recognition Task, Remembering Test Directions, Spoken Language, Comprehension and Word-Finding Difficulty. The score ranges from 0 to 70. A 4-point ADAS-cog change at 6 months is clinically meaningful.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Multiple-Domain Cognitive Dysfunction</measure>
    <time_frame>Baseline, at 6 months (immediately after the 6-month intervention), at 7 months (1 month post-intervention) and 9-months (3 months post-intervention).</time_frame>
    <description>The Digit Symbol Substitution Test (a subtest of the Wechsler Adult Intelligence Scale - Revised) is a measure of attention, transcription and speed of processing. Scoring is based on the total number of correct responses generated during a 90-sec time interval. Higher values reflect better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Executive control/spatial selective attention</measure>
    <time_frame>Baseline, at 6 months (immediately after the 6-month intervention), at 7 months (1 month post-intervention) and 9-months (3 months post-intervention).</time_frame>
    <description>The Flanker Test is a measure of speed of processing, attention and inhibitory control. Scoring is based on accuracy and reaction time. Lower values reflect better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Scale</measure>
    <time_frame>Baseline, at 6 months (immediately after the 6-month intervention), at 7 months (1 month post-intervention) and 9-months (3 months post-intervention).</time_frame>
    <description>The Quality of Life - Alzheimer's Disease, self-reported includes 13 items representing physical, social and psychological well-being. The administration takes about 5 minutes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depressive Symptoms</measure>
    <time_frame>Baseline, at 6 months (immediately after the 6-month intervention), at 7 months (1 month post-intervention) and 9-months (3 months post-intervention).</time_frame>
    <description>Changes in depressive symptoms assessed using the 15 item Geriatric Depression Scale, scores range from 0 (not depressed) to 15 (depressed).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tolerability of the study intervention: number of side effects and adverse events</measure>
    <time_frame>Baseline, at 6 months (immediately after the 6-month intervention), at 7 months (1 month post-intervention) and 9-months (3 months post-intervention).</time_frame>
    <description>Determined as number of side effects and adverse events related, probably related or possibly related to the study intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient's satisfaction: 8-item tDCS User Survey</measure>
    <time_frame>Baseline, at 6 months (immediately after the 6-month intervention)</time_frame>
    <description>Patient's satisfaction with the study intervention determined from the 8-item tDCS User Survey at the end of the intervention. Each item of the Survey is a brief statement and a respondent indicates if s/he Strongly Agree, Agree, Neither Agree or Disagree, Disagree or Strongly Disagree with the statement. Higher number of Agree/Strongly Agree ratings reflects higher satisfaction with the tDCS procedure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional Neuroplasticity-Digit Symbol Substitution</measure>
    <time_frame>Baseline, at 6 months (immediately after the 6-month intervention) and 9-months (3 months post-intervention).</time_frame>
    <description>The investigators will examine intervention-related changes in functional activation/deactivation networks during Digit Symbol Substitution Test. The investigators predict tDCS-related changes in functional/deactivation relative to sham - particularly in dorsolateral prefrontal cortex and associated networks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional Neuroplasticity - Flanker Interference Task</measure>
    <time_frame>Baseline, at 6 months (immediately after the 6-month intervention) and 9-months (3 months post-intervention).</time_frame>
    <description>The investigators will examine intervention-related changes in functional activation/deactivation networks during Flanker tests. The investigators predict tDCS-related changes in functional/deactivation relative to sham - particularly in dorsolateral prefrontal cortex and associated networks.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Structural Neuroplasticity</measure>
    <time_frame>Baseline, at 6 months (immediately after the 6-month intervention) and 9-months (3 months post-intervention).</time_frame>
    <description>The investigators propose to explore pre-post changes in structural connectivity as a function of tDCS. Structural changes in white matter integrity have been observed following tDCS in another study. Based on these initial findings, the investigators propose to monitor structural changes in white matter integrity (fractional anisotropy) using FreeSurfer's v.6.0 Tracts Constrained by Underlying Anatomy (TRACULA).</description>
  </other_outcome>
  <other_outcome>
    <measure>Durability of Global Cognitive Performance</measure>
    <time_frame>Baseline and 9-months (3 months post-intervention).</time_frame>
    <description>Change in The Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) was developed as an outcome measure for dementia interventions; its primary purpose was to be an index of global cognition in response to therapies. It assesses multiple cognitive domains across 11 items: Word Recall Task, Naming Objects and Fingers, Following Commands, Constructional Praxis, Ideational Praxis, Orientation, Word Recognition Task, Remembering Test Directions, Spoken Language, Comprehension and Word-Finding Difficulty. The score ranges from 0 to 70. A 4-point ADAS-cog change at 6 months is clinically meaningful.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Alzheimer Disease</condition>
  <condition>Dementia</condition>
  <arm_group>
    <arm_group_label>Active tDCS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The active tDCS will involve 30-minutes of direct current at intensity of 2 milliamperes (mA).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham tDCS</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Sham stimulation consists of the direct current ramped up to 2mA over 30 seconds, ramped down over 30 seconds and stay at 0 current for the remaining application period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>tDCS device model Soterix mini-CT (Soterix Medical Inc., New York, NY) programed to deliver active tDCS.</intervention_name>
    <description>At-home remotely supervised tDCS delivered over the dorsolateral prefrontal cortex with the anode on the left, cathode on the right, at an intensity of 2 mA, delivered for 30 minutes five times per week (Monday-Friday) for 26 weeks (6 months).</description>
    <arm_group_label>Active tDCS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>tDCS device model Soterix mini-CT (Soterix Medical Inc., New York, NY) programed to deliver sham tDCS.</intervention_name>
    <description>Sham treatment will consist of the current ramped up to 2mA over 30 seconds, ramped down over 30 seconds and stay at 0 current for the remaining time of the 30-minute application period five times per week (Monday-Friday) for 26 weeks (6 months).</description>
    <arm_group_label>Sham tDCS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Community-dwelling male or female of age 60 and older.&#xD;
&#xD;
          2. AD diagnosed by neurologists or geriatricians at our dementia and geriatric clinical&#xD;
             sites. Clinicians will review the medical records of all potential cases to ensure the&#xD;
             patients meet established clinical criteria for AD, and also examine individuals as&#xD;
             needed to further establish the diagnosis. Mild-to moderate stage AD as determined by&#xD;
             study clinicians using the Clinical Dementia Rating Scale (CDR). The CDR is a 5-point&#xD;
             scale used to characterize six domains of cognitive and functional performance&#xD;
             applicable to AD: Memory, Orientation, Judgment &amp; Problem Solving, Community Affairs,&#xD;
             Home &amp; Hobbies, and Personal Care. The necessary information to make each rating is&#xD;
             obtained through a semi-structured interview of the patient and a reliable informant&#xD;
             (e.g., family member). A CDR score of 0.5 or 1 is rated as mild severity and a score&#xD;
             of 2 is rated as moderate severity. The investigators selected mild to moderate AD&#xD;
             patients as our target population as they are the most prevalent AD severity group&#xD;
             referred to our clinics, increasing generalizability. This mild to moderate AD group&#xD;
             is also most likely to be cared for in the community and at home, in contrast to more&#xD;
             advanced or severe AD stages, which are more prevalent in institutional settings (and&#xD;
             will be the focus of our future studies).&#xD;
&#xD;
          3. If on dementia medication regimen, the regimen is stable for at least 4 weeks prior to&#xD;
             enrollment. The investigators will not restrict clinicians from starting, adjusting or&#xD;
             stopping dementia medications over the intervention period in keeping with the&#xD;
             pragmatic nature of our trial, but will account for medications in both groups in our&#xD;
             analysis.&#xD;
&#xD;
          4. Able to speak and understand English or Spanish at a level sufficient undergo the&#xD;
             study procedures and testing protocols.&#xD;
&#xD;
          5. Willing to complete an MRI (exclusions relevant to neuroimaging are described below).&#xD;
&#xD;
          6. Able to provide Informed Consent (or able to provide assent with a legal surrogate&#xD;
             providing informed consent.)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unstable medical or major psychiatric illnesses or unstable treatments for medical or&#xD;
             major psychiatric illnesses. Any medical or psychiatric diagnosis is permitted as long&#xD;
             as it has been clinically stable for at least 3 months, reflected in part by stability&#xD;
             of treatments for at least 3 months, and is expected on the basis of clinical judgment&#xD;
             to be in a stable phase that will likely extend for 6 months.&#xD;
&#xD;
          2. History of head trauma, seizures, brain surgery, stroke or cancer affecting head,&#xD;
             metal implants in the head or neck, compromised integrity or sensitivity of the skin&#xD;
             at or near locations where electrodes will be placed (e.g., eczema, severe rashes,&#xD;
             blisters, open wounds, burn including sunburns, cuts or irritation).&#xD;
&#xD;
          3. Currently participating in another intervention study or using neurostimulation&#xD;
             device.&#xD;
&#xD;
          4. Exclusions specific to neuroimaging procedure: the presence of any surgically&#xD;
             implanted metallic devices, such as aneurysm clips or pacemakers that would be a&#xD;
             safety contraindication for MRI. Subjects with large amounts of dental or surgical&#xD;
             hardware in the head and neck will be excluded because magnetic susceptibility effects&#xD;
             will lead to severe image artifacts in these subjects' images. Due to the confined&#xD;
             space of the MRI magnet, subjects with a known history of claustrophobia will also be&#xD;
             excluded as will subjects with weight &gt;350lbs or waist circumference &gt;55 inches.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joe Verghese, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Albert Einstein College of Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Helena Knotkova, PhD, DPhil</last_name>
    <role>Principal Investigator</role>
    <affiliation>Albert Einstein College of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Joe Verghese, MBBS</last_name>
    <phone>(718) 430-3877</phone>
    <email>joe.verghese@einsteinmed.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Emmeline Ayers, MPH</last_name>
    <phone>(718) 430-3835</phone>
    <email>emmeline.ayers@einsteinmed.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Albert Einstein College of Medicine</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Emmeline Ayers, MPH</last_name>
      <phone>718-430-3835</phone>
      <email>emmeline.ayers@einsteinmed.org</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Gulley E, Verghese J, Blumen HM, Ayers E, Wang C, Portenoy RK, Zwerling JL, Weiss E, Knotkova H. Neurostimulation for cognitive enhancement in Alzheimer's disease (the NICE-AD study): a randomized clinical trial. Neurodegener Dis Manag. 2021 Aug;11(4):277-288. doi: 10.2217/nmt-2020-0061. Epub 2021 Jul 9.</citation>
    <PMID>34240627</PMID>
  </reference>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>June 21, 2023</last_update_submitted>
  <last_update_submitted_qc>June 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Alzheimer's Disease</keyword>
  <keyword>transcranial direct current stimulation (tDCS)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04404153
org study id: 2020-11274
nct id: NCT04404153
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
is us export: Yes
The prevalence of Alzheimer's Disease (AD) is rising, but existing medications provide only
      modest control of cognitive decline and associated symptoms, and novel therapies are urgently
      needed. This randomized sham-controlled trial will determine if an innovative low-risk
      remotely-supervised transcranial Direct Current Stimulation (tDCS) applied over the area of
      the dorsolateral prefrontal cortex for 30 minutes at the intensity of 2 mA five times per
      week for 6 months at home can improve cognitive performance and symptoms and modulate
      neuroimaging markers of neuroplasticity in 100 patients with mild to moderate AD. If
      effective, this novel intervention can substantially enhance AD symptom management at home,
      improve quality of life of AD patients and their families, and reduce burden associated with
      this debilitating illness.
The hallmark of Alzheimer's Disease (AD) is cognitive decline with varied associated symptoms
      and signs. Unfortunately, there is no cure as yet for AD. Available treatments, including 5
      FDA-approved medications, have limited efficacy in terms of slowing pathological progression
      or controlling the symptoms and signs of cognitive decline in AD patients. Given the high
      burdens and costs of AD, and the therapeutic limitations, the development of novel treatment
      approaches for AD is of the highest importance for patients, families, medical providers, and
      society. This randomized controlled trial will determine if innovative, low-risk
      neurostimulation at home for 6 months can improve cognitive performance and symptoms in
      patients with mild to moderate AD.

      The primary objective is to determine the effects produced by 6 months of active tDCS or sham
      delivered over dorsolateral prefrontal cortex (DLPFC) in home settings on global cognitive
      performance (assessed by ADAS-Cog test - primary outcome), and secondarily on executive
      control/spatial selective attention (Eriksen Flanker Test), depressed mood (Geriatric
      depression scale), quality of life (Quality of Life Questionnaire-Alzheimer's Disease), and
      patient satisfaction with both the device and procedure (Neurostimulation User's Survey), in
      mild-to-moderate AD patients (n=100). The investigators also aim to determine functional and
      structural brain connectivity/network changes in response to the study intervention using
      functional Magnetic Resonance Imaging (fMRI; during rest and during executive function
      tasks), diffusion-weighted imaging (DWI), and multivariate covariance-based analytic
      approaches. Lastly, the investigators aim to examine time characteristics (durability) of the
      tDCS behavioral and neuroplasticity effects for up to 3 months following the intervention
      period.

      The intervention will consist of remotely supervised active tDCS stimulation and sham tDCS
      stimulation over the area of the dorsolateral prefrontal cortex, applied at home for 30
      minutes 5 times per week for 6 months. Participants randomized to the active tDCS will
      receive at each application 30 minutes of direct current stimulation at the intensity of 2
      mA. Participants randomized to the sham group will receive sham tDCS which consists of
      current ramped up to 2mA over 30 seconds, ramped down over 30 seconds and stay at 0 current
      for the remaining time of the 30-minute application.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Global Cognitive Performance
time frame: Baseline, at 6 months (immediately after the 6-month intervention)
description: Change in The Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) was developed as an outcome measure for dementia interventions; its primary purpose was to be an index of global cognition in response to therapies. It assesses multiple cognitive domains across 11 items: Word Recall Task, Naming Objects and Fingers, Following Commands, Constructional Praxis, Ideational Praxis, Orientation, Word Recognition Task, Remembering Test Directions, Spoken Language, Comprehension and Word-Finding Difficulty. The score ranges from 0 to 70. A 4-point ADAS-cog change at 6 months is clinically meaningful.
measure: Multiple-Domain Cognitive Dysfunction
time frame: Baseline, at 6 months (immediately after the 6-month intervention), at 7 months (1 month post-intervention) and 9-months (3 months post-intervention).
description: The Digit Symbol Substitution Test (a subtest of the Wechsler Adult Intelligence Scale - Revised) is a measure of attention, transcription and speed of processing. Scoring is based on the total number of correct responses generated during a 90-sec time interval. Higher values reflect better outcome.
measure: Executive control/spatial selective attention
time frame: Baseline, at 6 months (immediately after the 6-month intervention), at 7 months (1 month post-intervention) and 9-months (3 months post-intervention).
description: The Flanker Test is a measure of speed of processing, attention and inhibitory control. Scoring is based on accuracy and reaction time. Lower values reflect better outcome.
measure: Quality of Life Scale
time frame: Baseline, at 6 months (immediately after the 6-month intervention), at 7 months (1 month post-intervention) and 9-months (3 months post-intervention).
description: The Quality of Life - Alzheimer's Disease, self-reported includes 13 items representing physical, social and psychological well-being. The administration takes about 5 minutes.
measure: Depressive Symptoms
time frame: Baseline, at 6 months (immediately after the 6-month intervention), at 7 months (1 month post-intervention) and 9-months (3 months post-intervention).
description: Changes in depressive symptoms assessed using the 15 item Geriatric Depression Scale, scores range from 0 (not depressed) to 15 (depressed).
measure: Tolerability of the study intervention: number of side effects and adverse events
time frame: Baseline, at 6 months (immediately after the 6-month intervention), at 7 months (1 month post-intervention) and 9-months (3 months post-intervention).
description: Determined as number of side effects and adverse events related, probably related or possibly related to the study intervention.
measure: Patient's satisfaction: 8-item tDCS User Survey
time frame: Baseline, at 6 months (immediately after the 6-month intervention)
description: Patient's satisfaction with the study intervention determined from the 8-item tDCS User Survey at the end of the intervention. Each item of the Survey is a brief statement and a respondent indicates if s/he Strongly Agree, Agree, Neither Agree or Disagree, Disagree or Strongly Disagree with the statement. Higher number of Agree/Strongly Agree ratings reflects higher satisfaction with the tDCS procedure.
measure: Functional Neuroplasticity-Digit Symbol Substitution
time frame: Baseline, at 6 months (immediately after the 6-month intervention) and 9-months (3 months post-intervention).
description: The investigators will examine intervention-related changes in functional activation/deactivation networks during Digit Symbol Substitution Test. The investigators predict tDCS-related changes in functional/deactivation relative to sham - particularly in dorsolateral prefrontal cortex and associated networks.
measure: Functional Neuroplasticity - Flanker Interference Task
time frame: Baseline, at 6 months (immediately after the 6-month intervention) and 9-months (3 months post-intervention).
description: The investigators will examine intervention-related changes in functional activation/deactivation networks during Flanker tests. The investigators predict tDCS-related changes in functional/deactivation relative to sham - particularly in dorsolateral prefrontal cortex and associated networks.
measure: Structural Neuroplasticity
time frame: Baseline, at 6 months (immediately after the 6-month intervention) and 9-months (3 months post-intervention).
description: The investigators propose to explore pre-post changes in structural connectivity as a function of tDCS. Structural changes in white matter integrity have been observed following tDCS in another study. Based on these initial findings, the investigators propose to monitor structural changes in white matter integrity (fractional anisotropy) using FreeSurfer's v.6.0 Tracts Constrained by Underlying Anatomy (TRACULA).
measure: Durability of Global Cognitive Performance
time frame: Baseline and 9-months (3 months post-intervention).
description: Change in The Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) was developed as an outcome measure for dementia interventions; its primary purpose was to be an index of global cognition in response to therapies. It assesses multiple cognitive domains across 11 items: Word Recall Task, Naming Objects and Fingers, Following Commands, Constructional Praxis, Ideational Praxis, Orientation, Word Recognition Task, Remembering Test Directions, Spoken Language, Comprehension and Word-Finding Difficulty. The score ranges from 0 to 70. A 4-point ADAS-cog change at 6 months is clinically meaningful.
arm group label: Active tDCS
arm group type: Experimental
description: The active tDCS will involve 30-minutes of direct current at intensity of 2 milliamperes (mA).
arm group label: Sham tDCS
arm group type: Sham Comparator
description: Sham stimulation consists of the direct current ramped up to 2mA over 30 seconds, ramped down over 30 seconds and stay at 0 current for the remaining application period.
intervention type: Device
intervention name: tDCS device model Soterix mini-CT (Soterix Medical Inc., New York, NY) programed to deliver active tDCS.
description: At-home remotely supervised tDCS delivered over the dorsolateral prefrontal cortex with the anode on the left, cathode on the right, at an intensity of 2 mA, delivered for 30 minutes five times per week (Monday-Friday) for 26 weeks (6 months).
arm group label: Active tDCS
intervention type: Device
intervention name: tDCS device model Soterix mini-CT (Soterix Medical Inc., New York, NY) programed to deliver sham tDCS.
description: Sham treatment will consist of the current ramped up to 2mA over 30 seconds, ramped down over 30 seconds and stay at 0 current for the remaining time of the 30-minute application period five times per week (Monday-Friday) for 26 weeks (6 months).
arm group label: Sham tDCS
criteria: 
gender: All
minimum age: 60 Years
maximum age: 99 Years
healthy volunteers: No
last name: Joe Verghese, MBBS
role: Principal Investigator
affiliation: Albert Einstein College of Medicine
last name: Helena Knotkova, PhD, DPhil
role: Principal Investigator
affiliation: Albert Einstein College of Medicine
last name: Joe Verghese, MBBS
phone: (718) 430-3877
email: joe.verghese@einsteinmed.org
last name: Emmeline Ayers, MPH
phone: (718) 430-3835
email: emmeline.ayers@einsteinmed.org
facility: 
status: Recruiting
contact: 
country: United States
citation: Gulley E, Verghese J, Blumen HM, Ayers E, Wang C, Portenoy RK, Zwerling JL, Weiss E, Knotkova H. Neurostimulation for cognitive enhancement in Alzheimer's disease (the NICE-AD study): a randomized clinical trial. Neurodegener Dis Manag. 2021 Aug;11(4):277-288. doi: 10.2217/nmt-2020-0061. Epub 2021 Jul 9.
PMID: 34240627
responsible party type: Sponsor
mesh term: Alzheimer Disease
sharing ipd: No