HD-tDCS + mCILT for Primary Progressive Aphasia

Overseen By Megan Hoffman, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Disqualifiers: Stroke, Epilepsy, Pacemaker, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 28

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new ways to help people with primary progressive aphasia (PPA), a condition affecting language due to brain changes. Researchers are testing a combination of brain stimulation therapy (High-definition tDCS) and language therapy (Modified Constraint-Induced Language Therapy) to determine if it improves language skills. Participants will receive either the real treatment or a sham (fake) version for comparison. Individuals who have difficulty speaking or finding words due to specific types of PPA and have a high school education might be suitable for this study. The goal is to assess whether this approach can improve daily communication. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in PPA treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that HD-tDCS + mCILT is safe for individuals with primary progressive aphasia?

Research has shown that high-definition transcranial direct current stimulation (HD-tDCS) is generally safe. Studies have found it well-tolerated by individuals with primary progressive aphasia (PPA), a condition affecting language skills. Reports of side effects are few and usually mild, such as slight tingling or itching at electrode sites.

Modified Constraint-Induced Language Therapy (mCILT) is also considered safe. It aims to improve language skills by encouraging communication and has been successfully used in various language therapy programs. Studies have not reported any major safety concerns with mCILT.

Overall, current research suggests that combining HD-tDCS and mCILT is safe. However, ongoing studies will provide more information on how people respond to these treatments over time. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Primary Progressive Aphasia because they combine innovative techniques. High-definition transcranial direct current stimulation (HD-tDCS) uses a targeted electrical current to stimulate brain regions associated with language, which is a novel approach compared to standard speech therapies. Meanwhile, Modified Constraint-Induced Language Therapy (mCILT) focuses on intensive language practice, pushing patients to use verbal communication more actively than traditional therapies. Together, these methods aim to enhance language recovery by directly engaging the brain's plasticity and promoting active language use, offering hope for more effective interventions in a condition with limited treatment options.

What evidence suggests that HD-tDCS + mCILT could be effective for primary progressive aphasia?

Research has shown that high-definition transcranial direct current stimulation (HD-tDCS), which participants in this trial may receive, can improve language skills in people with primary progressive aphasia (PPA). For example, studies have found that HD-tDCS can help patients find the right words, which is crucial for communication. Additionally, past patients experienced language improvements with transcranial direct current stimulation (tDCS). Modified Constraint-Induced Language Therapy (mCILT), which all participants in this trial will undergo, is a well-researched method that encourages patients to practice speaking, thereby improving their language skills over time. Together, these treatments aim to boost language function by stimulating the brain and actively involving patients in speech exercises. ^{1 2 3 6 7}

Who Is on the Research Team?

Roy Hamilton, PhD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for native English speakers who can understand the study and consent to participate, diagnosed with nonfluent agrammatic PPA or logopenic variant PPA, and have at least a high school education. It's not for those with skull breaches, other neurological issues like stroke or brain injury, epilepsy/seizures history, pacemakers/ICDs, or small vessel disease.

Inclusion Criteria

I understand the study and can give my consent.

I am a native English speaker.

High school education (or more)

Exclusion Criteria

I have small vessel disease.

I have had a stroke or traumatic brain injury.

I have had surgery on my skull.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline Assessment

Baseline language assessment and MRI scanning

1 week

2 visits (in-person)

Treatment

Participants receive 10 daily sessions of HD-tDCS or sham stimulation paired with mCILT

2 weeks

9 visits (in-person)

Immediate Post-Treatment Assessment

Follow-up language assessment and MRI immediately after treatment

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

3 visits (in-person)

Crossover Treatment

Participants crossover to the alternate treatment arm and receive 10 daily sessions of HD-tDCS or sham stimulation paired with mCILT

2 weeks

9 visits (in-person)

Crossover Follow-up

Follow-up language assessment and MRI after crossover treatment

12 weeks

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• High-definition tDCS
• Modified Constraint-Induced Language Therapy

Trial Overview The study tests if language therapy combined with electrical brain stimulation (HD-tDCS) improves language in people with certain types of aphasia. Participants receive real or fake treatments over 10 days and are assessed immediately after and again three months later to see which works better.

How Is the Trial Designed?

Group I: HD-tDCS+mCILT Active Control 2 Interventions

Participants will undergo 10 daily sessions (Monday-Friday, x2 weeks) of HD-tDCS for 20 minutes using a montage in which a central electrode (1.5mA) is placed over the left frontotemporal area and four surrounding cathodes (.375mA each). Subjects will participate in a modified constraint-induced language therapy.

Group II: Sham+mCILT Placebo Group 2 Interventions

Participants will undergo 10 daily sessions (Monday-Friday, x2 weeks) of sham for 20 minutes using a montage in which a central electrode is placed over the left frontotemporal area and four surrounding cathodes. Subjects will participate in a modified constraint-induced language therapy,

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

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) 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]

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]

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]

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]

Citations

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

High-definition brain stimulation targeting separate regions ... High-definition brain stimulation targeting separate regions leads to differential word retrieval outcomes in patients with primary progressive ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04046991?term=AREA%5BConditionSearch%5D(Frontotemporal%20Dementia)%20AND%20AREA%5BOverallStatus%5D(ACTIVE_NOT_RECRUITING)&rank=10

Treating Primary Progressive Aphasia (PPA) Using High- ... Data collected at the beginning of a clinical study for all participants and for each arm or comparison group. These data include demographics, such as age, sex ...

3. 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).

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

Behavioral and neural effects of temporoparietal high ... Behavioural and neurophysiological responses to written naming treatment and high definition tDCS: a case study in advanced primary progressive aphasia.

5. repository.upenn.edu repository.upenn.edu/entities/publication/0eca30a6-8498-4046-a532-469875b0e211

A Comparative Case Study of the Efficacy of High-Definition ... This study reports data from two participants in an ongoing clinical trial: one with logopenic variant PPA (lvPPA) and one with nonfluent/ ...

6. mdpi.com mdpi.com/2077-0383/14/9/3063

Safety and Efficacy of Different Therapeutic Interventions ... Background: Primary progressive aphasia (PPA) is a neurodegenerative disorder that worsens over time without appropriate treatment.

7. 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.