Transcranial Direct Current Stimulation in the Treatment of Primary Progressive Aphasia

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified March 2026 by Johns Hopkins University
Sponsor
Johns Hopkins University
Information Provided by (Responsible Party)
Johns Hopkins University
Clinicaltrials.gov Identifier
NCT05386394
Other Study ID Numbers:
IRB00326681
First Submitted
May 12, 2022
First Posted
May 22, 2022
Last Update Posted
May 4, 2026
Last Verified
March 2026

ClinicalTrials.gov processed this data on April 2026Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Aim 1: To determine whether tDCS over the left perisylvian language areas paired with naming treatment will improve oral and written naming outcomes in two variants of PPA (nfvPPA and lvPPA).

The investigators will use a double-blind, sham-controlled, within-subject, cross-over design. Participants will receive Naming and Spelling (NASP) treatment + tDCS condition or NASP treatment + sham condition, in Period 1 or 2, randomized for the Period 1 stimulation condition. Each treatment period will last 3 weeks, with 5 language therapy sessions/week, for 15 sessions in total, and a 3-month (stimulation-free) wash-out time between the two periods of stimulation to evaluate clinically meaningful effects.

Language therapy (NASP treatment) will be delivered by a speech-language pathologist or a trained research associate. The participant will be shown a picture on the screen, asked to orally name it, and subsequently write the name. If the participant cannot, the participant will be asked to provide 3 semantic attributes to reinforce semantic representations, as in Semantic Feature Analysis treatment (Boyle, 2010). If the word still cannot be named or written, the clinician will provide the correct name and spelling and the participant will be asked to repeat or copy it 3 times, in a spell-study-spell procedure (Rapp \& Glucroft, 2009). There will be two word-sets: trained (targeted during therapy) and untrained (not targeted during therapy), both individually tailored to the participant based on severity of spelling deficit. Treatment stimuli will consist of 10-30 words depending on individual severity. General procedures and the outcome measure (letter accuracy) will be maintained across all participants. Consistent with the investigators previous work, the NASP treatment will be conducted in English, which, for most participants, will be the participant's first language.

To deliver tDCS, the investigators will use the Soterix 1x1 platform. The anode will be placed over the left frontal lobe, centered on F7 in the 10-20 electrode placement system (Homan, 1988), and cathode will be placed over the right cheek. Non-metallic, conductive rubber electrodes (5 cm x 5 cm), fitted with saline-soaked sponges to limit skin-electrode reactions will be used so the full left inferior frontal gyrus (IFG) will be covered. Current will be delivered with an intensity of 2 mA (estimated current density 0.08 milliamps (mA)/cm2) for a total of 20 minutes each tDCS session. Delivery of tDCS will be simultaneous with the start of language therapy, which will continue for an additional 25 minutes beyond the cessation of tDCS in each session. In contrast to actual tDCS, sham stimulation involves the delivery of 30 seconds of current ramping up to 2 mA and back down to 0 mA simultaneous with the start of language therapy.

Behavioral/language assessments will involve: oral and written naming, spelling, connected speech/discourse, sentence comprehension and production, verbal fluency, short-term/working memory tasks, etc. Other global cognitive assessments will be conducted, as well as quality of life assessments. Bilingual assessments will be conducted for those who bilingual or multilingual.

Aim 2: To identify clinical, neural, cognitive, biological, and demographic predictors of tDCS vs sham effects on primary outcomes.

Imaging will be performed at before Period 1, before Period 2 and 3-months post Period 2 for a total of 3 scans per participant. Scans will be done on a 3T Philips system and will consist of magnetization prepared rapid gradient echoresting state (MPRAGE), resting state functional MRI (rsfMRI), and diffusion tensor imaging (DTI). Each scanning session will last approximately 1 hour.

Saliva samples will be collected for exploratory analysis and DNA will be extracted using standard methodology. Genotyping will be carried out by the Johns Hopkins DNA Diagnostic Laboratory using standard methods.

Condition or DiseaseIntervention/Treatment
Primary Progressive AphasiaLogopenic Progressive AphasiaNon-Fluent Primary Progressive Aphasia
Device: Active tDCS + Language TherapyDevice: Active tDCS + Language Therapy

Study Design

Study TypeInterventional
Actual Enrollment180 participants
Design AllocationRandomized
Interventional ModelCrossover Assignment
MaskingTriple
Primary PurposeTreatment
Official TitlePhase II Clinical Trial of Transcranial Direct Current Stimulation in the Treatment of Primary Progressive Aphasia
Study Start DateFebruary 12, 2024
Actual Primary Completion Date1yr 8mos from now
Actual Study Completion Date1yr 8mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Active tDCS + Language Therapy first
Active tDCS will be applied at the beginning of 45 minutes language therapy session and will last for 20 minutes.
Device: Active tDCS + Language Therapy
Active tDCS 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 (inferior frontal gyrus). The stimulation will be delivered at an intensity of 2mA (estimated current density 0.04 milliamps (mA)/cm2; estimated total charge 0.048 Coulombs (C)/cm2) in a ramp-like fashion for a maximum of 20 minutes. Language therapy will be conducted in conjunction with stimulation and will target oral and written naming.
Sham tDCS + Language Therapy first
Sham tDCS will be applied at the beginning of 45 minutes language therapy session.
Device: Active tDCS + Language Therapy
Active tDCS 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 (inferior frontal gyrus). The stimulation will be delivered at an intensity of 2mA (estimated current density 0.04 milliamps (mA)/cm2; estimated total charge 0.048 Coulombs (C)/cm2) in a ramp-like fashion for a maximum of 20 minutes. Language therapy will be conducted in conjunction with stimulation and will target oral and written naming.

Outcome Measures

Primary Outcome Measures
  1. Immediate Change in Phonemic Accuracy
    The primary outcome measure will be tDCS-induced change in performance on phonemic accuracy of trained items. Phonemic accuracy will be calculated on a scale of 0-100% with a higher number reflecting higher accuracy. The change in performance from baseline will be compared between the tDCS condition and the sham condition.
  2. Immediate Change in Letter Accuracy
    The primary outcome measure will be tDCS-induced change in performance on letter accuracy of trained items. Letter accuracy will be calculated on a scale of 0-100% with a higher number reflecting higher accuracy. The change in performance from baseline will be compared between the tDCS condition and the sham condition.
  3. Change in Phonemic Accuracy at 3-month follow-up visit
    The primary outcome measure will be tDCS-induced change in performance on phonemic accuracy of trained items, 3 months following the discontinuation of intervention. Phonemic accuracy will be calculated on a scale of 0-100% with a higher number reflecting higher accuracy. The change in performance from baseline will be compared between the tDCS condition and the sham condition.
  4. Change in Letter Accuracy at 3-month follow-up visit
    The primary outcome measure will be tDCS-induced change in performance on letter accuracy of trained items, 3 months following the discontinuation of intervention. Letter accuracy will be calculated on a scale of 0-100% with a higher number reflecting higher accuracy. The change in performance from baseline will be compared between the tDCS condition and the sham condition.
Secondary Outcome Measures
  1. Change in Untrained Naming Items (phonemic accuracy)
    The outcome measure will be tDCS-induced change of phonemic accuracy of untrained stimuli (those not targeted in therapy). Phonemic accuracy will be calculated on a scale of 0-100% with a higher number reflecting higher accuracy. The change in performance from baseline will be compared between the tDCS condition and the sham condition.
  2. Change in Untrained Naming Items (letter accuracy)
    The outcome measure will be tDCS-induced change of letter accuracy of untrained stimuli (those not targeted in therapy). Letter accuracy will be calculated on a scale of 0-100% with a higher number reflecting higher accuracy. The change in performance from baseline will be compared between the tDCS condition and the sham condition.
  3. 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.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersYes
Inclusion Criteria
Presence of aphasia attributable to non-fluent PPA or logopenic PPA
High school education (or more)
Between the ages of 50 and 90
Must be able to understand the nature of the study and give informed consent
Exclusion Criteria
Cognitive impairment of sufficient severity to preclude giving informed consent (Mini Mental State Examination \[MMSE\] less than 15)
Any unrelated neurologic or physical condition that impairs communication ability
History of unrelated neurological conditions, including but not limited to traumatic brain injury (TBI), stroke, or small vessel disease, that has resulted in a neurologic deficit
Any additional neurological condition that would likely reduce the safety of study participation, including central nervous system (CNS) vasculitis, intracranial tumor, intracranial aneurysm, multiple sclerosis, or arteriovenous malformations
A medically unstable cardiopulmonary or metabolic disorder
Individuals with pacemakers or implantable cardiac defibrillators
Terminal illness associated with survival of less than 12 months
Major active psychiatric illness that may interfere with required study procedures or treatments, as determined by the enrolling physician
Current abuse of alcohol or drugs, prescription or otherwise
Participant in another drug, device, or biologics trial within 30 days prior to enrollment
Nursing a child, pregnant, or intending to become pregnant during the study
Left-handedness Exclusion for tDCS, specifically:
History of spontaneous or partial complex seizures or unexplained loss of consciousness within 6 months of enrollment
Subjects with metallic objects in the face or head other than dental apparatus, such as braces, fillings, or implants
Subjects with previous craniotomy or any breach in the skull Exclusion for MRI, specifically:
Presence of any of the following devices: cardiac pacemaker, other pacemakers (for carotid sinus, insulin pumps, nerve stimulators, lead wires or similar wires), optic implant, implanted cardiac defibrillator, aneurysm clip, any electronically/magnetically/mechanically activated implant, ferromagnetic implants (coils, filters, stents; metal sutures or staples)
Presence of any of the following: pregnancy, claustrophobia, metal in eye or orbit, tattooed eyeliner

Contacts and Locations

Sponsors and CollaboratorsJohns Hopkins University
Locations
Johns Hopkins Hospital | Baltimore Maryland, United States, 21287University of Pennsylvania | Philadelphia Pennsylvania, United States, 19104Baycrest Centre for Geriatric Care | Toronto Ontario, Canada, M6A 2E1
Investigators
Principal Investigator: Kyrana Tsapkini, PhD., Johns Hopkins University