AzTrials
AzTrials

Alzheimer Disease, Early OnsetNCT04122001

Effects of Electrical Stimulation on Verbal Learning in Typical and Atypical Alzheimer's Disease

A study testing Active, in-person HD-tDCS or active remote tDCS and Word List Learning Intervention (WordLLI) in people with Alzheimer Disease, Early Onset and Atypical Alzheimer's Disease, run by Johns Hopkins University at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

Alzheimer's disease (AD) is the leading neurodegenerative disease of aging characterized by multiple cognitive impairments. Given the recent failures of disease-modifying drugs, the current focus is on preventing or mitigating synaptic damage that correlates with cognitive decline in AD patients. Read more about this study

Who is it for?
Ages 45 to 85 yearsHealthy volunteers can take part
What is being tested?
Active, in-person HD-tDCS or active remote tDCS and Word List Learning Intervention (WordLLI)
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
90 participants
Where
1 siteUnited States
Study dates
17 Aug 2020to 30 Nov 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 to 85 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • For the aphasic/atypical AD participants:
  • Must be between 45-85 years of age.
  • Must be right-handed.
  • Must be proficient in English.
  • Must have a minimum of high-school education.
  • Must be diagnosed as logopenic variant Primary Progressive Aphasia (PPA) with Alzheimer's Disease (AD) biomarkers. Other possible diagnosis for the 'aphasic AD' variant would be Mild Cognitive Impairment (MCI) or 'possible AD' according to 2011 guidelines with AD biomarkers (CSF or positron emission tomography (PET) amyloid-beta or fluorodeoxyglucose (FDG)-positron emission tomography (PET) with unihemispheric atrophy).
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  • Participants will be diagnosed from PPA and early dementias clinics at Johns Hopkins University or other specialized centers in US using current consensus criteria. Diagnosis will be based on neuropsychological testing, language testing (most commonly the Western Aphasia Battery), MRI and clinical assessment. The investigators will also use two new variant classification tests the investigators have developed at the lab which discriminate PPA variants with great accuracy (above 80%): a spelling test and a speech production test (i.e.,Cookie Theft picture description task).
  • For the amnesic/typical AD participants:
  • Must be between 45-85 years of age.
  • Must be right-handed.
  • Must be proficient in English.
  • Must have a minimum of high-school education.
  • Must be diagnosed with 'probable AD' in specialized diagnostic centers with neuropsychological (e.g., RAVLT) and AD biomarkers according to 2011 guidelines.
  • The investigators will also perform extensive testing in the investigators' test battery including the Mnemonic Similarity Test (MST) that discriminates and measures the most salient hippocampal deficit-pattern separation (PS).

Who cannot join

  • People with previous neurological disease including vascular dementia (e.g., stroke, developmental dyslexia, dysgraphia or attentional deficit).
  • People with hearing loss (> 25 decibel, using audiometric hearing screen).
  • People with uncorrected visual acuity loss.
  • People with advanced dementia or severe language impairments (MMSE < 15, or Montreal Cognitive Assessment <10, or language Frontotemporal Dementia-specific Clinical Dementia Rating (FTD-CDR) = 3).
  • Left handed individuals.
  • People with pre-existing psychiatric disorders such as behavioral disturbances, severe depression, or schizophrenia that do not allow these people to comply or follow the study schedule and requirements such as repeated evaluation and therapy.
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  • People with severe claustrophobia.
  • People with cardiac pacemakers or ferromagnetic implants.
  • Pregnant women.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Johns Hopkins Hospital

    Baltimore, Maryland, 21287

Other trials in United States

About this study

Official title: Transcranial Direct Current Stimulation in Typical and Atypical Alzheimer's Disease

Alzheimer's disease (AD) is the leading neurodegenerative disease of aging characterized by multiple cognitive impairments. Given the recent failures of disease-modifying drugs, the current focus is on preventing or mitigating synaptic damage that correlates with cognitive decline in AD patients. Transcranial Direct Current Stimulation (tDCS) is a safe, non-invasive, non-painful electrical stimulation of the brain that is shown to act as a primer at the synaptic level when administered along with behavioral therapy, mostly involving language, learning and memory. Previous studies have shown that tDCS over the left angular gyrus (AG) improves language associative learning in the elderly through changes in functional connectivity between the AG and the hippocampus. The investigators' previous clinical trial on the effects of tDCS in neurodegenerative disorders has also shown augmented effects of lexical retrieval for tDCS. In the present study the investigators will compare the effects of active vs. sham tDCS over the AG-an area that is part of the default mode network but also a language area, particularly important for semantic integration and event processing-in two predominant AD variants: probable AD with amnesic phenotype (amnesic/typical AD) and probable AD with non-amnesic (language deficit) phenotype also described as logopenic variant PPA with AD pathology (aphasic/atypical AD). The investigators aim to: (1) determine whether active high-definition tDCS (HD-tDCS) targeting the left AG combined with a Word-List Learning Intervention (WordLLI) will improve verbal learning; (2) identify the changes in functional connectivity between the stimulated area (AG) and other structurally and functionally connected areas using resting-state functional magnetic resonance imaging; (3) identify changes in the inhibitory neurotransmitter GABA at the stimulation site using magnetic resonance spectroscopy. Furthermore, the investigators need to determine the characteristics of the people that may benefit from the new neuromodulatory approaches. For this reason, the investigators will evaluate neural and cognitive functions as well as physiological characteristics such as sleep, and will analyze the moderating effects on verbal learning outcomes. Study results can help provide treatment alternatives as well as a better understanding of the therapeutic and neuromodulatory effects of tDCS in AD, thus improving patients' and caregivers' quality of life.

Read the detailed description

The investigation implements a double-blind, sham-controlled, within-subject, cross-over design that allows for the evaluation of the cognitive and neural effects of word-list learning as modulated by tDCS compared to sham stimulation. Participants in all groups will receive word-list learning intervention (WordLLI)+ High-Definition tDCS (HD-tDCS) or WordLLI+ sham in Period 1 or 2, randomized for the Period 1 stimulation condition. Each learning Period will last 2 weeks, with 5 learning sessions per week (for a total of 10 learning sessions per Period) with a 3-month (stimulation-free) wash-out period between the two Periods. The intensity, total number of learning sessions and number of learning items is consistent with most other tDCS studies in neurodegenerative disorders and the investigators have used this design successfully over the past 7 years in neurodegenerative disorders (PPA, mild AD). Stimulation is implemented every weekday to take advantage of the long-term potentiation induced by tDCS as found in early multi-session studies. A tDCS-only condition (without any intervention) is not implemented in this design because no study to date has shown improvement on motor, cognitive, or language performance after anodal tDCS-only for 2 or even more weeks. After each period the investigators will perform 1-month and 3-month follow-up sessions for evaluation purposes. For those participants who are long-distance, at the 1-month time point only the investigators may use a video conferencing tool such as GoToMeeting to administer the assessments. This is to mitigate the costs of travel for a short appointment.

Being tested
Active, in-person HD-tDCS or active remote tDCS, Sham, Word List Learning Intervention (WordLLI)
Keywords
transcranial direct current stimulation (tDCS), Alzheimer's Disease (AD), verbal learning treatment, word list learning, logopenic Progressive Aphasia, episodic memory
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Active, in-person HD-tDCS or active remote tDCSDevice

    Stimulation will be delivered by a battery-driven constant current stimulator. The electrical current will be administered to a pre-specified region of the brain (angular gyrus). 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. In the active, in-person HD-tDCS the current is delivered in a ring configuration. In the active remote tDCS current is delivered in one electrode patch.

  • ShamDevice

    Current will be administered in a ramp-like fashion but after the ramping the intensity will drop to 0 mA. Current under the Sham condition will last for a maximum of 30 seconds.

  • Word List Learning Intervention (WordLLI)Other

    Participants will receive a word list learning intervention (WordLLI) of semantically related and unrelated word lists. Word lists are presented across 10 trials, with an additional trial after a 10-minute delay to assess delayed recall. Immediately following verbal presentation of word lists during each trial, participants will be instructed to recall as many of the words from the list as possible. Participants may use the written modality as a strategy during recall. Word lists include 12 words matched based on psycholinguistics attributes (e.g., imageability, frequency). This task is designed to help participants improve memory via enhancing list learning capabilities.

Study groups in NCT04122001
Study groupRoleWhat they receive
Active HD-tDCS+word intervention then Sham+word interventionExperimentalParticipants will receive active HD-tDCS + Word List Learning Intervention (WordLLI) and then receive Sham + WordLLI after a three-month washout period.
Receives: Device: Active, in-person HD-tDCS or active remote tDCS; Device: Sham; Other: Word List Learning Intervention (WordLLI)
Sham+word intervention then active HD-tDCS+word interventionExperimentalParticipants will receive Sham + Word List Learning Intervention (WordLLI) and then active HD-tDCS + WordLLI after a three-month washout period.
Receives: Device: Active, in-person HD-tDCS or active remote tDCS; Device: Sham; Other: Word List Learning Intervention (WordLLI)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in auditory recall accuracy based on the sum of words recalled in Trials 1-5 of semantically related - trained word-lists

    Each trained word-list (practiced during the intervention period) will consist of 12 semantically related words (e.g., birds). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to learn each list. The investigators will compute the raw score of items correctly recalled by summing all scores from Trial 1 to Trial 5 and transforming to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  2. Change in auditory delayed recall accuracy of semantically related - trained word-lists

    Each trained word-list (practiced during the intervention period) will consist of 12 semantically related words (e.g., birds). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to recall each list, and then participants will be asked to recall that list 20 minutes later (delayed recall). The investigators will compute the raw score of items correctly recalled (delayed recall) and transform to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  3. Change in auditory recall accuracy based on the sum of words recalled in Trials 1-5 of semantically unrelated - trained word-lists

    Each trained word-list (practiced during the intervention period) will consist of 12 semantically unrelated words (as in RAVLT). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to learn each list. The investigators will compute the raw score of items correctly recalled by summing all scores from Trial 1 to Trial 5 and transforming to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  4. Change in auditory delayed recall accuracy of semantically unrelated - trained word-lists

    Each trained word-list (practiced during the intervention period) will consist of 12 semantically unrelated words (as in RAVLT). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to recall each list, and then participants will be asked to recall that list 20 minutes later (delayed recall). The investigators will compute the raw score of items correctly recalled (delayed recall) and transform to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  5. Change in auditory recall accuracy based the sum of words recalled in Trials 1-5 of semantically related - untrained word-lists

    Each untrained word-list (not practiced during the intervention period) will consist of 12 semantically related words (e.g., birds). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to learn each list. The investigators will compute the raw score of items correctly recalled by summing all scores from Trial 1 to Trial 5 and transforming to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  6. Change in auditory delayed recall accuracy of semantically related - untrained word-lists

    Each untrained word-list (not practiced during the intervention period) will consist of 12 semantically related words (e.g., birds). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to recall each list, and then participants will be asked to recall that list 20 minutes later (delayed recall). The investigators will compute the raw score of items correctly recalled (delayed recall) and transform to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  7. Change in auditory recall accuracy based on the sum of words recalled in Trials 1-5 of semantically unrelated - untrained word-lists

    Each untrained word-list (not practiced during the intervention period) will consist of 12 semantically unrelated words (as in RVLT). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to learn each list. The investigators will compute the raw score of items correctly recalled by summing all scores from Trial 1 to Trial 5 and transforming to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  8. Change in auditory delayed recall accuracy of semantically unrelated - untrained word-lists

    Each untrained word-list (not practiced during the intervention period) will consist of 12 semantically unrelated words (as in RVLT). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to recall each list, and then participants will be asked to recall that list 20 minutes later (delayed recall). The investigators will compute the raw score of items correctly recalled (delayed recall) and transform to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

Secondary outcomes (25)

  1. Change in Rey Auditory-Verbal Learning Test (RAVLT) score

    RAVLT is a well-established verbal memory test. RAVLT includes a 5-trial presentation of a 15-word list (List A), a single presentation of an interference list (List B)(Trial 6), two post-interference recall trials (one immediate - Trial 7, one delayed - Trial 8) and recognition of the target words in the orthographic modality with distractors (Trial 9). Scoring includes the percent score of Trial 1, Trial 5, Trial 8 and Trial 9 as well as the sum of Trial 1 through 5, and the difference between Trial 5 and Trial 1 computed as the percent difference between the scores before intervention and each time point after. Increase in score is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  2. Change in Mini Mental State Examination (MMSE)

    MMSE is a well-established cognitive assessment test. It examines functions including registration (repeating named prompts), attention and calculation, recall, language, ability to follow simple commands and orientation. The total raw score is out of 30 points. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  3. Change in Mnemonic Similarity Task (MST) score

    MST is a well-established test in order to assess high interference memory and general recognition memory via pattern separation. It involves differentiating between previously learned images and novel images. For the MST tasks, the Pattern Separation (PS) score will be calculated using two measures: a) the rate of similar items correctly identified minus the rate of similar items misidentified as new (S|S-S|N); b) the rate of similar items correctly identified minus the rate of similar items misidentified as old (S|S-O|S). The number of correct responses for each category of items (i.e., old, similar, new) and the type of errors (i.e., identifications of new items as similar; identification of similar items as old) will also be tracked. Change in outcome in percent difference will be computed between the scores before intervention and each time point after. Increase in scores is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  4. Change in word repetition score

    Temple Assessment of Language and Short-Term Memory in Aphasia (TALSA) tasks include word repetition, with sets of 1-6 words. Scoring will be based on percent of words correctly repeated. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  5. Change in non-word repetition score

    TALSA tasks include non-word repetition, with sets of 1-6 non-words. Scoring will be based on percent of non-words correctly repeated. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  6. Change in sentence repetition score

    Sentence repetition tasks come from the TALSA, with scoring based on percent of words in sentences correctly repeated. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  7. Change in oral naming Boston Naming Test score

    Accuracy in oral picture naming (30-item Boston Naming Test) will be compared for tDCS and sham conditions. The Boston Naming Test is a widely used picture naming test that detects lexical retrieval deficits in the oral modality. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  8. Change in oral naming Philadelphia Naming Test score

    Accuracy in oral picture naming (Philadelphia Naming Test) will be compared for tDCS and sham conditions. The Philadelphia Naming Test is an extensive picture naming test that comprises 275 items from a wide range of frequencies and other psycholinguistic characteristics. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  9. Change in written naming as assessed by Boston Naming Test

    Accuracy in written picture naming (30-item Boston Naming Test) will be compared for tDCS and sham conditions. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  10. Change in written naming as assessed by Philadelphia Naming Test

    Accuracy in written picture naming (Philadelphia Naming Test) will be compared for tDCS and sham conditions. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  11. Change in oral naming of action as assessed by Hopkins Assessment of Naming Actions (HANA)

    Accuracy in oral naming of actions will be compared for tDCS and sham conditions. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  12. Change in syntactic comprehension as assessed by Subject-relative, Object-relative, Active, Passive (S.O.A.P.) Syntactic Battery

    The 40-item Subject-relative, Object-relative, Active, Passive (S.O.A.P.) Syntactic Battery of various sub-tests will be used to assess argument structure comprehension and production. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between baseline and each time point. Increase in score is considered benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  13. Change in verbal fluency task score

    Verbal fluency tasks (semantic and letter fluency) involve generating as many words as possible in one minute. Scoring will be based on number of words generated per minute. The investigators will compute the raw score of items correct and compute change in outcome between baseline and each time point. Increase in score is considered benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  14. Change in spelling as assessed by the Johns Hopkins Dysgraphia battery

    Accuracy in spelling using the Johns Hopkins Dysgraphia battery will be compared for tDCS and sham conditions. The investigators will compute the raw score of items correct using a spelling scoring system accounting for additions, substitutions, and deletions, and transform to percent correct (range: 0-100%), computing change in outcome in percent difference before intervention and each time point after. Increase in score is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  15. Change in digit span forward score

    Digit span forward involves the recall of a series of single digits (sets of 1-8 digits) in the same order the digits were presented. Scoring will be based on the number of consecutive digits correctly recalled. The investigators will compute the change in outcome between the time point before intervention and each time point after. Increase in score is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  16. Change in digit span backward score

    Digit span backward involves the recall of a series of single digits (sets of 1-8 digits) in the reverse order than the digits were presented. Scoring will be based on the number of consecutive digits correctly recalled. The investigators will compute the change in outcome between the time point before intervention and each time point after. Increase in score is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  17. Change in spatial span forward score

    Spatial span forward involves the recall of a series of positions on a board (sets of 1-9) in the same order the digits were presented. Scoring will be based on the number of consecutive positions correctly recalled. The investigators will compute the change in outcome between the time point before intervention and each time point after. Increase in score is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  18. Change in spatial span backward score

    Spatial span backward involves the recall of a series of positions (sets of 1-8) in the reverse order than the digits were presented. Scoring will be based on the number of consecutive positions correctly recalled. The investigators will compute the change in outcome between the time point before intervention and each time point after. Increase in score is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  19. Change in semantic content of connected speech

    Using the Cookie Theft image from the Boston Diagnostic Aphasia Examination (BDAE) and the Circus image from the Apraxia Battery for Adults (ABA) investigators will obtain representative language samples as participants describe the images. The investigators will compute the raw score of items (semantics) correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  20. Change in attention and manipulation of information scores

    Using the Trail Making Test (TMT) parts A and B, which include the sequential connection of letters/numbers in order to complete a trail, the investigators will obtain the time required by the participants to finish the tasks. Decrease in the time is considered a benefit.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  21. Change in volumetric measurements of select brain regions

    Using Magnetization-Prepared Rapid Gradient-Echo (MPRAGE) Magnetic Resonance Imaging (MRI) investigators will perform volumetric measurements of select brain regions. Measurements will be collected in millimeters cubed (mm^3).

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  22. Change in functional connectivity of select brain regions (z-correlations)

    Using resting stage functional MRI (rs-fMRI) investigators will detect activity of various brain regions under a resting/task-negative condition, which will help evaluate functional regional interactions as indicated by the z-correlations between the selected brain area.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  23. Change in Gamma-Aminobutyric Acid (GABA) concentration

    Using Magnetic Resonance Spectroscopy (MRS) investigators will measure metabolite (GABA) concentrations from select brain regions in international units (IU).

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  24. Change in location of white matter tracts of select brain regions

    Using Diffusion Tensor Imaging (DTI) investigators will estimate the location of the brain's white matter tracts on the regions of concern.

    Measured: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

  25. Change in anisotropy of white matter tracts of select brain regions

    Using Diffusion Tensor Imaging (DTI) investigators will estimate the anisotropy of the brain's white matter tracts on the brain regions of concern.

    Measured: Before intervention, immediately after intervention and 3 months post intervention, up to 31 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Oct 2019
  2. Study start17 Aug 2020
  3. Primary completion30 Nov 2026 (estimated)
  4. Study completion30 Nov 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
This is a crossover design of active High-Definition tDCS (HD-tDCS) + Word List Learning Intervention (WordLLI) that crossovers to sham + WordLLI in Arm 1, and sham +WordLLI that crossovers to active HD-tDCS + WordLLI in Arm 2.
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04122001
Sponsor's protocol ID
IRB00229164
Other IDs
5R01AG068881
Status last verified
Jul 2026
First submitted
8 Oct 2019
Last updated
15 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Tsapkini K, Frangakis C, Gomez Y, Davis C, Hillis AE. Augmentation of spelling therapy with transcranial direct current stimulation in primary progressive aphasia: Preliminary results and challenges. Aphasiology. 2014;28(8-9):1112-1130. doi: 10.1080/02687038.2014.930410.

    PubMed 26097278

  • Tsapkini K, Webster KT, Ficek BN, Desmond JE, Onyike CU, Rapp B, Frangakis CE, Hillis AE. Electrical brain stimulation in different variants of primary progressive aphasia: A randomized clinical trial. Alzheimers Dement (N Y). 2018 Sep 5;4:461-472. doi: 10.1016/j.trci.2018.08.002. eCollection 2018.

    PubMed 30258975

  • Ficek BN, Wang Z, Zhao Y, Webster KT, Desmond JE, Hillis AE, Frangakis C, Vasconcellos Faria A, Caffo B, Tsapkini K. The effect of tDCS on functional connectivity in primary progressive aphasia. Neuroimage Clin. 2018 May 21;19:703-715. doi: 10.1016/j.nicl.2018.05.023. eCollection 2018.

    PubMed 30009127

  • Reis J, Schambra HM, Cohen LG, Buch ER, Fritsch B, Zarahn E, Celnik PA, Krakauer JW. Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation. Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1590-5. doi: 10.1073/pnas.0805413106. Epub 2009 Jan 21.

    PubMed 19164589

  • Huey ED, Probasco JC, Moll J, Stocking J, Ko MH, Grafman J, Wassermann EM. No effect of DC brain polarization on verbal fluency in patients with advanced frontotemporal dementia. Clin Neurophysiol. 2007 Jun;118(6):1417-8. doi: 10.1016/j.clinph.2007.02.026. Epub 2007 Apr 23. No abstract available.

    PubMed 17452012

  • Antal A, Terney D, Poreisz C, Paulus W. Towards unravelling task-related modulations of neuroplastic changes induced in the human motor cortex. Eur J Neurosci. 2007 Nov;26(9):2687-91. doi: 10.1111/j.1460-9568.2007.05896.x. Epub 2007 Oct 26.

    PubMed 17970738

  • Segrave RA, Arnold S, Hoy K, Fitzgerald PB. Concurrent cognitive control training augments the antidepressant efficacy of tDCS: a pilot study. Brain Stimul. 2014 Mar-Apr;7(2):325-31. doi: 10.1016/j.brs.2013.12.008. Epub 2013 Dec 19.

    PubMed 24486425

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Questions about this trial

What is this clinical trial studying?

A study testing Active, in-person HD-tDCS or active remote tDCS and Word List Learning Intervention (WordLLI) in people with Alzheimer Disease, Early Onset and Atypical Alzheimer's Disease, run by Johns Hopkins University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 15 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in auditory recall accuracy based on the sum of words recalled in Trials 1-5 of semantically related - trained word-lists (time frame: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04122001, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2026.

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