NCT03887481

Targeting Language-specific and Executive-control Networks With Transcranial Direct Current Stimulation in Logopenic Variant PPA

Recruiting now NA Last updated 15 September 2025

What this trial tests

NA trial testing High-definition active tDCS (HD-tDCS) + "Repeat After Me" (RAM) Treatment in Logopenic Progressive Aphasia in 60 participants. Currently enrolling.

Timeline

15 October 2022

Primary endpoint
31 October 2027

31 October 2027

Quick facts

Lead sponsor	Johns Hopkins University
Phase	NA
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	triple
Primary purpose	treatment
Enrollment	60
Start date	15 October 2022
Primary completion	31 October 2027
Estimated completion	31 October 2027
Sites	1 location across United States

Drugs / interventions tested

• High-definition active tDCS (HD-tDCS) + "Repeat After Me" (RAM) Treatment
• Sham + "Repeat After Me" (RAM) Treatment

Conditions studied

• Logopenic Progressive Aphasia — all drugs for Logopenic Progressive Aphasia →
• Primary Progressive Aphasia — all drugs for Primary Progressive Aphasia →

Sponsor

Johns Hopkins University

Who can join

Adults 50 to 80, any sex, with Logopenic Progressive Aphasia or Primary Progressive Aphasia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

AD afflicts over 5.5. million Americans and is one of the most expensive diseases worldwide. In AD the variant in which language functions are most affected are referred to as 'logopenic variant Primary Progressive Aphasia' (lvPPA). Language deficits dramatically impair communication and quality of life for both patients and caregivers. PPA usually has an early onset (50-65 years of age), detrimentally affecting work and family life. Studies have identified verbal short-term memory/working memory (vSTM/WM) as a primary deficit and cause of language impairment. In the first cycle of this award, the investigators asked the question of whether language therapy effects could be augmented by electrical stimulation. The investigators conducted the largest to-date randomized, double-blind, sham-controlled, crossover, clinical trial to determine the effects of transcranial direct current stimulation (tDCS) in PPA. The investigators found that tDCS over the left inferior frontal gyrus (L\_IFG), one of the major language hubs in the brain, significantly enhanced the effects of a written naming and spelling intervention. In addition, findings demonstrated that tDCS modulates functional connectivity between the stimulated area and other networks (e.g. functionally and structurally connected areas), and that tDCS modulates the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). In terms of tDCS, the investigators have been identified several predictors to determine the beneficience of tDCS including (a) PPA variant, (b) initial performance on cognitive/language tasks, particularly vSTM/WM, and (c) initial white-matter integrity and structure. These findings support the notion that tDCS benefits generalize beyond the treatment tasks and has led to the important question of the present study: How can we implement treatments to product benefits that maximally generalize to untrained but vital language/cognitive functions.

To address the above question, the investigators will test recent neuroplasticity theories that claim that the benefits of neuromodulation to language-specific areas generalize to other language functions within the language network, while neuromodulation of a domain-general/multiple-demands area generalizes to both domain-general, executive and language functions. The two areas to be stimulated will be the supramarginal gyrus (SMG) and left dorsolateral prefrontal cortex (DLPFC) respectively. The left supramarginal gyrus (L\_SMG) in particular, specializes in phonological processing, namely phonological verbal short-term memory (vSTM), i.e., the ability to temporarily store phonological (and graphemic) information in order. The domain of vSTM affects many language tasks (repetition, naming, syntax), which makes it an ideal treatment target and the L\_SMG an ideal stimulation target, since generalization of tDCS effects to other language tasks is driven by the function (computation) of the stimulated area. By testing a fundamental principle of neuromodulation in a devastating neurodegenerative disorder, the investigators will significantly advance the field of neurorehabilitation in early-onset dementias.

Aim 1: To determine whether vSTM/WM behavioral therapy combined with high definition (HD)-tDCS over the L\_SMG will induce more generalization to language-specific tasks than to executive tasks, whereas stimulation over the LDPFC will induce equivalent generalization to both executive and language-specific tasks.

Aim 2: To understand the mechanism of tDCS by measuring tDCS-induced changes in network functional connectivity (FC) and GABA in the LSMG and LDPFC. The investigators will carry out resting-state functional magnetic resonance imaging (rsfMRI), (MPRAGE), diffusion-weighted imaging (DWI), perfusion imaging (pCASL), and magnetic resonance spectroscopy (MRS), before, after, and 3-months post-intervention.

Aim 3: To identify the neural, cognitive, physiological, clinical and demographic characteristics (biomarkers) that predict sham, tDCS, and tDCS vs. sham effects on vSTM and related language tasks in PPA. The investigators will evaluate neural (functional and structural connectivity, cortical volume, neuropeptides, and perfusion), cognitive (memory, attention, executive) and language functions, clinical (severity), physiological (sleep), and demographic (age, gender) characteristics, and the investigators will analyze the effects on vSTM and other language/cognitive outcomes immediately after intervention and at 3 months post-intervention.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Non-pharmacological interventions for improving language and communication in people with primary progressive aphasia.
   Roheger M, Riemann S, Brauer A, McGowan E, et al · · 2024 · cited 13× · PMID 38808659 · DOI 10.1002/14651858.cd015067.pub2
2. Experimental Disease-Modifying Agents for Frontotemporal Lobar Degeneration.
   Giunta M, Solje E, Gardoni F, Borroni B, et al · · 2021 · cited 9× · PMID 33790662 · DOI 10.2147/jep.s262352
3. Verbal learning in logopenic variant Primary Progressive Aphasia: An EEG investigation.
   Neophytou K, Chriskos P, Gallegos J, Afthinos A, et al · · 2026 · PMID 41086585 · DOI 10.1016/j.neurobiolaging.2025.10.002
4. Written picture descriptions distinguish variants of primary progressive aphasia.
   Tippett DC, Surrao K, Neophytou K, Kim H, et al · · 2025 · PMID 40986290 · DOI 10.1177/13872877251376381
5. Letter to the Editor Response to: Is Transcranial Direct Current Stimulation Really Beneficial for Frontotemporal Dementia? (Published 12-18-2024).
   Tippett DC, Neophytou K, Tao Y, Gallegos J, et al · · 2025 · PMID 40453827 · DOI 10.1177/11795735251339997