HD-tDCS + Language Therapy for Primary Progressive Aphasia

Overseen By Kyrana Tsapkini, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Johns Hopkins University

Disqualifiers: Neurological disease, Hearing loss, Visual acuity loss, Advanced dementia, Psychiatric disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 3 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining language therapy with a non-invasive brain stimulation technique, high-definition transcranial direct current stimulation (HD-tDCS), can improve language skills in individuals with Primary Progressive Aphasia (PPA), a condition affecting language abilities and quality of life. Researchers are particularly interested in whether stimulating different brain areas can enhance both language and cognitive functions. Participants with PPA who are right-handed, proficient in English, and have at least a high-school education may be eligible to join. The trial will alternate between real and sham (placebo-like) stimulation to assess effectiveness. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance language and cognitive functions for those with PPA.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this method is safe for treating language deficits in primary progressive aphasia?

Research shows that high-definition transcranial direct current stimulation (HD-tDCS) is generally safe. Studies suggest that this brain stimulation can be a safe and possibly effective treatment, especially when combined with language therapy for conditions like primary progressive aphasia. Some people report mild side effects, such as tingling or itching on the scalp, but these are usually temporary and not serious. Overall, when used as part of a structured therapy plan, research has not identified any major safety concerns with HD-tDCS. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about HD-tDCS for Primary Progressive Aphasia because it offers a new way to stimulate the brain. Unlike traditional speech therapy alone, HD-tDCS uses a non-invasive brain stimulation technique that can enhance language therapy by targeting specific brain regions involved in language processing. This approach has the potential to improve language abilities more effectively and quickly than current methods, offering hope for better outcomes in individuals with this challenging condition.

What evidence suggests that HD-tDCS combined with language therapy could be effective for primary progressive aphasia?

Research has shown that high-definition transcranial direct current stimulation (HD-tDCS) can significantly enhance language skills in individuals with primary progressive aphasia (PPA). Studies have found that HD-tDCS, particularly when applied to critical language areas in the brain, improves abilities such as word fluency and spelling. Specifically, stimulating the left inferior frontal gyrus (LIFG), a key language area, has led to noticeable improvements. This trial will compare two treatment sequences: one where participants first receive active HD-tDCS with language/cognitive interventions, and another where they first receive Sham with language/cognitive interventions. This treatment also appears to enhance connectivity and communication between different brain regions, potentially extending language improvements to other tasks. Overall, evidence suggests that HD-tDCS is a promising method for enhancing language functions in PPA. ^{1 2 3 5 6}

Who Is on the Research Team?

Kyrana Tsapkini, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for right-handed individuals aged 50-80 with Primary Progressive Aphasia or dementia, who have completed at least high school and are proficient in English. They must be diagnosed at specialized clinics based on consensus criteria. Healthy controls matched by age and education may also participate.

Inclusion Criteria

I am between 50 and 80 years old.

You use your right hand more often than your left hand.

I have been diagnosed with Primary Progressive Aphasia or dementia.

Exclusion Criteria

People who are left-handed.

Are you right-handed?

Do you have a high-school level education?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Sham or active HD-tDCS combined with Language/Cognitive Interventions

3 months

Multiple visits for tDCS sessions and assessments

Washout

A washout period between crossover phases to eliminate carryover effects

3 months

Follow-up

Participants are monitored for changes in language and cognitive functions post-intervention

3 months

Assessments at 1 month and 3 months post-intervention

What Are the Treatments Tested in This Trial?

Interventions

• High-definition active tDCS (HD-tDCS)
• Sham

Trial Overview The study tests if brain stimulation combined with verbal memory therapy can improve language skills in people with PPA. It compares the effects of stimulating two different brain areas using HD-tDCS during a 'Repeat After Me' treatment versus a sham (placebo-like) procedure.

How Is the Trial Designed?

Group I: Sham + Language/Cognitive Intervention(s) first Experimental Treatment 2 Interventions

Participants will receive Sham + Language/Cognitive Intervention(s) first and then receive active HD-tDCS + Language/Cognitive Intervention(s) after a three-month washout period.

Group II: Active HD-tDCS + Language/Cognitive Intervention(s) first Experimental Treatment 2 Interventions

Participants will receive active HD-tDCS + Language/Cognitive Intervention(s) first and then receive Sham + Language/Cognitive Intervention(s) after a three-month washout period.

High-definition active tDCS (HD-tDCS) is already approved in United States for the following indications:

Approved in United States as High-definition transcranial direct current stimulation for:

• Investigational use in clinical trials for logopenic variant primary progressive aphasia (lvPPA)

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

A systematic review of 25 studies involving 471 participants found that Transcranial Direct Current Stimulation (tDCS) did not improve overall functional communication in stroke patients, indicating limited efficacy for this primary outcome.

However, anodal tDCS, especially when applied over the left inferior frontal gyrus, showed a significant improvement in noun naming performance, suggesting it may be a promising targeted treatment for specific language deficits after stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation (tDCS) for improving aphasia after stroke: a systematic review with network meta-analysis of randomized controlled trials. Elsner, B., Kugler, J., Mehrholz, J.[2020]

In a study involving 10 individuals undergoing standard aphasia therapy, 70% expressed interest in and were eligible for transcranial direct current stimulation (tDCS), which was administered during therapy sessions.

Data from four participants showed a large effect size (Cohen's d = 1.32) favoring active tDCS over sham stimulation, suggesting that tDCS may enhance communication outcomes in aphasia therapy, although one participant with severe deficits did not benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Feasibility of Combining Transcranial Direct Current Stimulation with Standard Aphasia Therapy. Duncan, ES., Nakkawita, SG.[2022]

In a study of 39 participants with primary progressive aphasia (PPA), both transcranial direct current stimulation (tDCS) and sham treatment improved language therapy outcomes, with tDCS showing greater benefits, especially for untrained words.

The integrity of white matter pathways in the brain was found to predict the effectiveness of tDCS in enhancing language therapy, suggesting that assessing white matter integrity could help identify patients who are more likely to benefit from these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

White Matter Integrity Predicts Electrical Stimulation (tDCS) and Language Therapy Effects in Primary Progressive Aphasia. Zhao, Y., Ficek, B., Webster, K., et al.[2021]

Transcranial Direct Current Stimulation (tDCS) shows promise in improving language outcomes for patients with Primary Progressive Aphasia (PPA), but the effectiveness can vary based on patient characteristics and stimulation protocols, as analyzed in 15 studies.

Despite generally positive results across studies, significant variability exists in treatment effects related to the specific PPA variant and stimulation parameters, indicating that further research is needed to optimize tDCS protocols for different patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of Transcranial Direct Current Stimulation in Primary Progressive Aphasia: Methodological Considerations. Coemans, S., Struys, E., Vandenborre, D., et al.[2022]

In a trial involving six patients with non-fluent primary progressive aphasia, two weeks of daily transcranial direct current stimulation (tDCS) led to improvements in speech production and grammatical comprehension.

The study suggests that tDCS could be a promising intervention for enhancing language abilities in PPA, warranting further research with larger, controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for the treatment of primary progressive aphasia: An open-label pilot study. Gervits, F., Ash, S., Coslett, HB., et al.[2022]

In a study involving individuals with Primary Progressive Aphasia (PPA), transcranial direct current stimulation (tDCS) showed potential to improve language abilities, particularly in those with more severe language deficits at baseline.

The study's results suggest that tDCS can enhance global language performance and specific language skills, indicating that the severity of language impairment may help predict which patients will benefit from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline Performance Predicts tDCS-Mediated Improvements in Language Symptoms in Primary Progressive Aphasia. McConathey, EM., White, NC., Gervits, F., et al.[2022]

Transcranial direct-current stimulation (tDCS) significantly improved articulatory accuracy in patients with aphasia after stroke, indicating its potential effectiveness in enhancing speech production.

While tDCS showed qualitative improvements in naming and syllable repetition tasks, these results were not statistically significant, suggesting that further research is needed to fully understand its impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Anodal tDCS on Articulatory Accuracy, Word Production, and Syllable Repetition in Subjects with Aphasia: A Crossover, Double-Blinded, Sham-Controlled Trial. Vila-Nova, C., Lucena, PH., Lucena, R., et al.[2021]

Transcranial direct current stimulation (tDCS) shows promise as an adjunct treatment for improving speech-language deficits in patients with chronic post-stroke aphasia and primary progressive aphasia, by enhancing cortical excitability in language areas.

Current research emphasizes the need for more studies to connect improvements in neuropsychological test performance with real-world functional communication outcomes, as most existing studies focus on impairment rather than practical communication skills.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation in post stroke aphasia and primary progressive aphasia: Current knowledge and future clinical applications. Sebastian, R., Tsapkini, K., Tippett, DC.[2019]

Transcranial direct current stimulation (tDCS) applied to 12 patients with semantic variant primary progressive aphasia (sv-PPA) showed significant improvements in semantic accuracy and processing speed, particularly for living categories in verbal tasks.

The study provides evidence for the effectiveness of tDCS in enhancing semantic processing in sv-PPA, supporting the idea of a left temporal-pole network for verbal semantics that can be modulated by targeted brain stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct current stimulation over the anterior temporal areas boosts semantic processing in primary progressive aphasia. Teichmann, M., Lesoil, C., Godard, J., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12484069/

High-definition brain stimulation targeting separate regions ... LIFG stimulation yielded statistically significant improvements in phonemic fluency at immediate post testing compared to baseline, with 25–50% ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0149763425002659

Linguistic effects of transcranial Direct Current Stimulation ... Transcranial Direct Current Stimulation (tDCS) has shown promising language improvements in patients with primary progressive aphasia (PPA).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05386394

Transcranial Direct Current Stimulation in the Treatment of ... Augmentation of spelling therapy with transcranial direct current stimulation in primary progressive aphasia: Preliminary results and challenges.

4. frontiersin.org frontiersin.org/journals/psychology/articles/10.3389/fpsyg.2025.1492447/full

Behavioral and neural effects of temporoparietal high ... Recently, transcranial direct current stimulation (tDCS) has emerged as a safe and potentially effective treatment option, particularly when given with language ...

5. mdpi.com mdpi.com/2076-3425/15/8/839

Efficacy of Transcranial Magnetic Stimulation and ... Conclusions: rTMS and tDCS applied with or without concomitant language treatment appear to be promising interventions for enhancing language abilities in PPA, ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2213158218301682

The effect of tDCS on functional connectivity in primary ... The present study tested whether the additional language gains with repetitive tDCS (over sham) in PPA are caused by changes in functional connectivity.