HD-tDCS + mCILT for Primary Progressive Aphasia

Overseen By Megan Hoffman, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

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

66 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a double-blind, sham-controlled, crossover study in which subjects with the non-fluent/agrammatic and logopenic variants of primary progressive aphasia (naPPA and lvPPA, respectively) will undergo language testing and structural and functional brain imaging before and after receiving 10 semi-consecutive daily sessions of real or sham high-definition transcranial direct current stimulation (HD-tDCS) paired with modified constraint-induced language therapy (mCILT). Language testing and brain imaging will be repeated immediately after completion of and 3 months following completion of treatment. The 3-month follow-up will be the primary endpoint. The investigators will examine changes in language performance induced by HD-tDCS + mCILT compared to sham HD-tDCS + mCILT. The investigators will also use network science to analyze brain imaging (fMRI) data to identify network properties associated with baseline PPA severity and tDCS-induced changes in performance. This study will combine knowledge gained from our behavioral, imaging, and network data in order to determine the relative degrees to which these properties predict whether persons with PPA will respond to intervention.

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 data supports the effectiveness of the treatment HD-tDCS + mCILT for Primary Progressive Aphasia?

Research suggests that transcranial direct current stimulation (tDCS), when combined with language therapy, can improve language abilities in people with Primary Progressive Aphasia (PPA). Studies have shown improvements in speech production and grammatical comprehension, indicating that tDCS may help some individuals with PPA, especially those with more severe language deficits at the start of treatment. ^{1 2 3 4 5}

Is HD-tDCS + mCILT safe for humans?

Transcranial direct current stimulation (tDCS), a component of the treatment, has been used in various studies and is generally considered safe for humans, with some studies showing improvements in language abilities for conditions like Primary Progressive Aphasia. However, more extensive and controlled studies are needed to fully understand its safety and effectiveness. ^{1 2 3 4 5}

How does the HD-tDCS + mCILT treatment differ from other treatments for primary progressive aphasia?

The HD-tDCS + mCILT treatment is unique because it combines high-definition transcranial direct current stimulation (HD-tDCS), which uses electrical currents to stimulate specific brain areas, with modified constraint-induced language therapy (mCILT), a language therapy that encourages patients to use verbal communication. This combination aims to improve language outcomes by enhancing brain connectivity and language function, which is different from traditional therapies that may not use electrical stimulation. ^{1 2 4 6 7}

Research Team

Roy Hamilton, PhD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

A Systematic Review of Transcranial Direct Current Stimulation in Primary Progressive Aphasia: Methodological Considerations. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for the treatment of primary progressive aphasia: An open-label pilot study. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

White Matter Integrity Predicts Electrical Stimulation (tDCS) and Language Therapy Effects in Primary Progressive Aphasia. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Baseline Performance Predicts tDCS-Mediated Improvements in Language Symptoms in Primary Progressive Aphasia. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Direct current stimulation over the anterior temporal areas boosts semantic processing in primary progressive aphasia. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

"The effect of tDCS on functional connectivity in primary progressive aphasia" NeuroImage: Clinical, volume 19 (2018), pages 703-715. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

The effect of tDCS on functional connectivity in primary progressive aphasia. [2021]