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Primary Progressive AphasiaPhase 2NCT05386394

Transcranial Direct Current Stimulation in the Treatment of Primary Progressive Aphasia

A Phase 2 study testing Active tDCS + Language Therapy in people with Primary Progressive Aphasia and Logopenic Progressive Aphasia, run by Johns Hopkins University at 3 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

While many have strongly suggested that transcranial direct current stimulation (tDCS) may represent a beneficial intervention for patients with primary progressive aphasia (PPA), this promising technology has not yet been applied widely in clinical settings. Read more about this study

Who is it for?
Ages 50 to 90 yearsHealthy volunteers can take part
What is being tested?
Active tDCS + Language Therapy
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
180 participants
Where
3 sitesin 2 countries
Study dates
13 Feb 2024to 1 Feb 2028
Phase
Phase 2
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 50 to 90 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 17Show fewer
  • 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
  • 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
  • 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

Trial locations and contacts

3 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Kelly Eun, B.S. contact

(410) 929 - 0279

krmeun@jhmi.edu

Kyrana Tsapkini, PhD. contact

410-736-2940

tsapkini@jhmi.edu

3 sites in 2 countries

United States2 sites, 2 recruiting
  • Johns Hopkins Hospital

    Baltimore, Maryland, 21287

    Kyrana Tsapkini, PhD, 410-736-2940, tsapkini@jhmi.edu

    Kyrana Tsapkini, PhD

    Recruiting
  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

    Daniela Sacchetti, MS, 215-573-8485, danielas@pennmedicine.upenn.edu

    Roy Hamilton, PhD

    Recruiting

Other trials in United States

Canada1 site, 1 recruiting
  • Baycrest Centre for Geriatric Care

    Toronto, Ontario, M6A 2E1

    Howard Chertkow, PhD, 416-785-2500, hchertkow@research.baycrest.org

    Howard Chertkow, PhD

    Recruiting

Other trials in Canada

About this study

Official title: Phase II Clinical Trial of Transcranial Direct Current Stimulation in the Treatment of Primary Progressive Aphasia

While many have strongly suggested that transcranial direct current stimulation (tDCS) may represent a beneficial intervention for patients with primary progressive aphasia (PPA), this promising technology has not yet been applied widely in clinical settings. This treatment gap is underscored by the absence of any neurally-focused standard-of-care treatments to mitigate the devastating impact of aphasia on patients' family, work, and social lives. Given that tDCS is inexpensive, easy to use (it is potentially amenable to home use by patients and caregivers), minimally invasive, and safe there is great promise to advance this intervention toward clinical use. The principal reason that tDCS has not found wide clinical application yet is that its efficacy has not been tested in large, multi-center, clinical trials. In this study, scientists in the three sites that have conducted tDCS clinical trials in North America-Johns Hopkins University and the University of Pennsylvania in the US, and the University of Toronto in Canada, will collaborate to conduct a multi-site, Phase II clinical trial of tDCS a population in dire need of better treatments.

Read the detailed 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.

Being tested
Active tDCS + Language Therapy, Sham tDCS + Language Therapy
Keywords
transcranial direct current stimulation, language treatment, primary progressive aphasia
Medical subject headings
Aphasia, Primary Progressive, Primary Progressive Nonfluent Aphasia

What participants receive

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

  • Active tDCS + Language TherapyDevice

    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 TherapyDevice

    During sham stimulation, current will be administered in a ramp-line fashion but after the ramping the intensity will drop to 0 mA. Language therapy targeting oral and written naming will be administered during sham tDCS stimulation.

Study groups in NCT05386394
Study groupRoleWhat they receive
Active tDCS + Language Therapy firstExperimentalActive tDCS will be applied at the beginning of 45 minutes language therapy session and will last for 20 minutes.
Receives: Device: Active tDCS + Language Therapy; Device: Sham tDCS + Language Therapy
Sham tDCS + Language Therapy firstSham comparatorSham tDCS will be applied at the beginning of 45 minutes language therapy session.
Receives: Device: Active tDCS + Language Therapy; Device: Sham tDCS + Language Therapy

What is being measured

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

  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.

    Measured: Baseline and Immediate follow-up of 3-week intervention period

  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.

    Measured: Baseline and Immediate follow-up of 3-week intervention period

  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.

    Measured: Baseline and 3 months post intervention

  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.

    Measured: Baseline and 3 months post intervention

Secondary outcomes (3)
  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.

    Measured: Baseline and 3 months post intervention

  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.

    Measured: Baseline and 3 months post intervention

  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.

    Measured: Immediate follow-up of 3-week intervention period and 3-month follow-up

Timeline

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

  1. First posted23 May 2022
  2. Study start13 Feb 2024
  3. Primary completion1 Feb 2028 (estimated)
  4. Study completion1 Feb 2028 (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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
This is a crossover design of tDCS + behavioral language therapy that crossovers to sham + behavioral language therapy in Arm 1, and sham + behavioral language therapy that crossovers to tDCS + behavioral language therapy in Arm 2.
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
180 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05386394
Sponsor's protocol ID
IRB00326681
Other IDs
1R01AG075111
Status last verified
Apr 2026
First submitted
13 May 2022
Last updated
5 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes

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
  • Roncero C, Kniefel H, Service E, Thiel A, Probst S, Chertkow H. Inferior parietal transcranial direct current stimulation with training improves cognition in anomic Alzheimer's disease and frontotemporal dementia. Alzheimers Dement (N Y). 2017 Mar 24;3(2):247-253. doi: 10.1016/j.trci.2017.03.003. eCollection 2017 Jun.

    PubMed 29067331
  • McConathey EM, White NC, Gervits F, Ash S, Coslett HB, Grossman M, Hamilton RH. Baseline Performance Predicts tDCS-Mediated Improvements in Language Symptoms in Primary Progressive Aphasia. Front Hum Neurosci. 2017 Jun 30;11:347. doi: 10.3389/fnhum.2017.00347. eCollection 2017.

    PubMed 28713256
  • Gervits F, Ash S, Coslett HB, Rascovsky K, Grossman M, Hamilton R. Transcranial direct current stimulation for the treatment of primary progressive aphasia: An open-label pilot study. Brain Lang. 2016 Nov;162:35-41. doi: 10.1016/j.bandl.2016.05.007. Epub 2016 Aug 12.

    PubMed 27522537
  • Roncero C, Service E, De Caro M, Popov A, Thiel A, Probst S, Chertkow H. Maximizing the Treatment Benefit of tDCS in Neurodegenerative Anomia. Front Neurosci. 2019 Nov 22;13:1231. doi: 10.3389/fnins.2019.01231. eCollection 2019.

    PubMed 31824242
  • 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
  • Boyle M. Semantic feature analysis treatment for aphasic word retrieval impairments: what's in a name? Top Stroke Rehabil. 2010 Nov-Dec;17(6):411-22. doi: 10.1310/tsr1706-411.

    PubMed 21239365
  • Rapp B, Glucroft B. The benefits and protective effects of behavioural treatment for dysgraphia in a case of primary progressive aphasia. Aphasiology. 2009 Feb 1;23(2):236-265. doi: 10.1080/02687030801943054.

    PubMed 21603153
  • Homan RW. The 10-20 electrode system and cerebral location. American Journal of EEG Technology. 1988;28(4):269-279.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Active tDCS + Language Therapy in people with Primary Progressive Aphasia and Logopenic Progressive Aphasia, run by Johns Hopkins University at 3 sites in 2 countries.

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 4 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States, Canada. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

Contact Kelly Eun, B.S. ((410) 929 - 0279, krmeun@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Immediate Change in Phonemic Accuracy (time frame: Baseline and Immediate follow-up of 3-week intervention period). The study lists 4 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 NCT05386394, which also lists 9 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 5 May 2026.

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