Transcranial Direct Current Stimulation in the Treatment of Primary Progressive Aphasia

NCT ID: NCT05386394

Last Updated: 2025-09-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

180 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-13

Study Completion Date

2028-02-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Primary Progressive Aphasia Logopenic Progressive Aphasia Non-Fluent Primary Progressive Aphasia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Active tDCS + Language Therapy

Intervention Type DEVICE

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

Intervention Type DEVICE

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.

Sham tDCS + Language Therapy first

Sham tDCS will be applied at the beginning of 45 minutes language therapy session.

Group Type SHAM_COMPARATOR

Active tDCS + Language Therapy

Intervention Type DEVICE

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

Intervention Type DEVICE

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.

Interventions

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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.

Intervention Type DEVICE

Sham tDCS + Language Therapy

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.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Presence of aphasia attributable to non-fluent PPA or logopenic PPA
* High school education (or more)
* Between the ages of 50 and 80
* 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
Minimum Eligible Age

50 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kyrana Tsapkini, PhD.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

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Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Baycrest Centre for Geriatric Care

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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United States Canada

Central Contacts

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Kelly Eun, B.S.

Role: CONTACT

(410) 929 - 0279

Kyrana Tsapkini, PhD.

Role: CONTACT

410-736-2940

Facility Contacts

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Kyrana Tsapkini, PhD

Role: primary

410-736-2940

Daniela Sacchetti, MS

Role: primary

215-573-8485

Howard Chertkow, PhD

Role: primary

416-785-2500

References

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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.

Reference Type BACKGROUND
PMID: 26097278 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29067331 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28713256 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27522537 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31824242 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30258975 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21239365 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21603153 (View on PubMed)

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

Reference Type BACKGROUND

Other Identifiers

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1R01AG075111

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00326681

Identifier Type: -

Identifier Source: org_study_id

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