TMS + Language Therapy for Aphasia

(TMS Trial)

Overseen By Daniela Sacchetti, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Disqualifiers: Substance abuse, Neurological disorders, Psychiatric disorders, 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: 15

Duration: 2 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining Transcranial Magnetic Stimulation (TMS) with Speech-Language Therapy (SLT) can improve speech and understanding in people with mild aphasia, a language disorder caused by a stroke. Researchers aim to determine if this combination is more effective than a placebo version of TMS, which mimics TMS but has no real effect. The trial seeks participants who had a stroke on the left side of their brain over six months ago, have mild aphasia, and can speak English. Participants will undergo 10 treatment sessions and follow-up assessments to evaluate progress. 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 early findings.

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 Transcranial Magnetic Stimulation combined with Speech-Language Therapy is safe for treating mild aphasia?

Research has shown that Transcranial Magnetic Stimulation (TMS) is generally safe for people. Studies have found that most patients tolerate TMS well when treating conditions like post-stroke aphasia, which involves difficulty with language after a stroke. One study found that TMS safely improved speech, particularly in understanding spoken words.

Another study demonstrated that TMS, when combined with intensive therapy, remained safe and practical, even during longer sessions. Common side effects include mild headaches or discomfort at the stimulation site, but serious side effects are rare.

Since TMS is already used for other conditions, such as depression, this further suggests its safety. Overall, TMS appears promising as a safe method for aiding language recovery after a stroke. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for aphasia?

Researchers are excited about using Transcranial Magnetic Stimulation (TMS) for treating aphasia because it offers a non-invasive approach that directly targets brain activity. Unlike traditional speech therapy, which primarily focuses on exercises to improve language skills, TMS uses magnetic fields to stimulate nerve cells in the brain regions responsible for language. This method has the potential to enhance the effectiveness of speech-language therapy by directly influencing brain function, potentially leading to faster and more significant improvements in language abilities.

What evidence suggests that TMS combined with SLT might be an effective treatment for mild aphasia?

In this trial, participants will be randomized into two groups to evaluate the effectiveness of Transcranial Magnetic Stimulation (TMS) combined with Speech-Language Therapy (SLT) for aphasia. Research has shown that using TMS along with SLT can aid individuals with aphasia, a language problem caused by brain damage. For those who experienced a stroke at least six months ago, TMS significantly improved language skills. One study found that TMS had both immediate and long-lasting positive effects on language recovery. Another study showed that low-frequency TMS, when used with SLT, improved language abilities in stroke patients with long-term aphasia. These findings suggest that TMS, combined with SLT, could effectively enhance speech and understanding in people with mild aphasia after a stroke. ^{2 3 6 7 8}

Who Is on the Research Team?

H. Branch Coslett, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for individuals with mild aphasia due to chronic stroke. Participants must complete a medical screening, be eligible based on their MRI results, and commit to 10 consecutive sessions of treatment along with follow-up assessments.

Inclusion Criteria

My stroke happened over 6 months ago.

I had a stroke affecting the left side of my brain.

Mild Aphasia (WAB AQ score > 85)

Exclusion Criteria

I have been diagnosed with tinnitus.

Ongoing substance or alcohol abuse

Active psychiatric disorders (e.g., bipolar disorder, schizophrenia)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline Assessment

Participants undergo a battery of tests to define their language function and a research MRI scan

1 week

1 visit (in-person)

Treatment

Participants receive 10 consecutive sessions of TMS and SLT treatment over 2 weeks

2 weeks

10 visits (in-person)

Follow-up

Participants complete follow-up assessments to monitor language functioning

4 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Speech-Language Therapy
• Transcranial Magnetic Stimulation

Trial Overview The study tests if Transcranial Magnetic Stimulation (TMS) combined with Speech-Language Therapy (SLT) can improve speech and comprehension in people with mild aphasia from stroke. It compares real TMS against sham TMS over two weeks of daily sessions.

How Is the Trial Designed?

Group I: Real TMS Experimental Treatment 2 Interventions

Some of our participants will be randomized to the real treatment arm where they will receive 10 sessions of real TMS paired with speech-language therapy.

Group II: Fake TMS Placebo Group 1 Intervention

Some of our participants will be randomized to the sham treatment arm where they will receive 10 sessions of fake TMS paired with speech-language therapy.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Temple University

Collaborator

Trials

321

Recruited

89,100+

National Institute on Deafness and Other Communication Disorders (NIDCD)

Collaborator

Trials

377

Recruited

190,000+

Published Research Related to This Trial

Repetitive transcranial magnetic stimulation (rTMS) has been shown to be more effective than sham rTMS and conventional rehabilitation for improving language recovery in stroke patients with aphasia, based on a meta-analysis of 28 studies involving 1287 patients.

Low-frequency rTMS specifically demonstrated greater improvements in language recovery, particularly in naming and comprehension, while high-frequency rTMS did not show significant benefits compared to sham or conventional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of repetitive transcranial magnetic stimulation (rTMS) on aphasia in stroke patients: A systematic review and meta-analysis. Zhang, J., Zhong, D., Xiao, X., et al.[2022]

The combination of 6-Hz-primed low-frequency rTMS and intensive speech therapy was safely administered to four post-stroke patients without any adverse effects during an 11-day treatment period.

All patients showed significant improvements in language function, indicating that this treatment protocol may be an effective option for enhancing recovery in individuals with post-stroke aphasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic application of 6-Hz-primed low-frequency rTMS combined with intensive speech therapy for post-stroke aphasia. Kakuda, W., Abo, M., Momosaki, R., et al.[2016]

In a study involving 24 post-stroke patients with aphasia, combining low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) with intensive speech therapy (ST) led to significant improvements in language abilities, particularly for nonfluent aphasic patients who showed enhanced auditory comprehension, reading comprehension, and repetition.

The targeted application of LF-rTMS based on fMRI findings suggests a tailored approach to treatment, with nonfluent patients benefiting from stimulation of the inferior frontal gyrus and fluent patients from stimulation of the superior temporal gyrus, indicating the potential of this method as a neurorehabilitative protocol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of low-frequency rTMS and intensive speech therapy in poststroke patients with aphasia: a pilot study based on evaluation by fMRI in relation to type of aphasia. Abo, M., Kakuda, W., Watanabe, M., et al.[2022]

The study involved two post-stroke patients with sensory-dominant aphasia who underwent 10 sessions of low-frequency rTMS targeting the Wernicke's area, combined with language therapy, demonstrating that this approach is safe and well-tolerated without adverse effects.

Both patients showed significant improvements in language function, as measured by the Token test and Standard Language Test of Aphasia, with benefits persisting for three months after treatment, indicating the efficacy of this combined therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-frequency rTMS with language therapy over a 3-month period for sensory-dominant aphasia: case series of two post-stroke Japanese patients. Kakuda, W., Abo, M., Uruma, G., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) applied at 1 Hz to the undamaged right hemisphere has shown long-term improvements in naming abilities for chronic stroke patients with nonfluent aphasia, suggesting a potential therapeutic approach for language recovery.

A case study indicated that combining rTMS with speech therapy (constraint-induced language therapy) may enhance the effectiveness of treatment, highlighting the importance of integrated rehabilitation strategies for stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation and aphasia rehabilitation. Naeser, MA., Martin, PI., Ho, M., et al.[2021]

In a study of 17 patients with chronic post-stroke aphasia, Intensive Language-Action Therapy (ILAT) significantly improved language performance, as measured by various tests, regardless of whether patients received real or sham transcranial magnetic stimulation (TMS).

The study found no significant benefit of TMS when combined with ILAT, suggesting that while ILAT is effective for language rehabilitation, TMS may not enhance its effects in chronic aphasia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining rTMS With Intensive Language-Action Therapy in Chronic Aphasia: A Randomized Controlled Trial. Heikkinen, PH., Pulvermüller, F., Mäkelä, JP., et al.[2020]

Repetitive transcranial magnetic stimulation (rTMS) has shown a significant positive effect on naming accuracy in stroke patients with aphasia, with a strong effect size (SMD = 1.26) based on a meta-analysis of 11 studies involving 242 patients.

The treatment was found to be safe, with no reported adverse effects, and it may enhance overall language function in patients with aphasia, suggesting its potential as a beneficial therapy alongside traditional speech and language therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of rTMS in patients with poststroke aphasia: a systematic review and focused meta-analysis. Gholami, M., Pourbaghi, N., Taghvatalab, S.[2022]

The study involving 20 stroke survivors demonstrated that combining repetitive transcranial magnetic stimulation (rTMS) with multi-modality aphasia therapy (M-MAT) is safe and feasible, with no adverse events reported.

While both treatment groups showed significant improvements in speech and language outcomes, there was no significant difference in effectiveness between the rTMS and sham groups, suggesting that personalized approaches may be needed based on individual lesion locations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) combined with multi-modality aphasia therapy for chronic post-stroke non-fluent aphasia: A pilot randomized sham-controlled trial. Low, TA., Lindland, K., Kirton, A., et al.[2023]

In a study involving 30 participants with subacute aphasia after stroke, those who received real repetitive transcranial magnetic stimulation (rTMS) combined with speech therapy showed significant improvements in all 10 measures of basic linguistic skills and functional communication, compared to only 6 measures in the sham group.

This research indicates that combining rTMS with behavioral language therapy can effectively enhance communication abilities in patients with subacute aphasia, marking a promising advancement in rehabilitation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Add-on Effects of Repetitive Transcranial Magnetic Stimulation on Subacute Aphasia Therapy: Enhanced Improvement of Functional Communication and Basic Linguistic Skills. A Randomized Controlled Study. Rubi-Fessen, I., Hartmann, A., Huber, W., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39999397/

Transcranial Magnetic Stimulation Combined With ... This study provides Class III evidence that in patients with aphasia 6 or more months after a stroke, 1-Hz rTMS combined with intensive M-MAT improves WAB-AQ ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2837379

Long-Term Therapy With Transcranial Magnetic ... Findings In this randomized clinical trial, which included 63 participants diagnosed with PPA, TMS administered over a 6-month period mitigated ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003999323006597

The Therapeutic Effect of Transcranial Magnetic ... The results showed that TMS treatment has significant immediate (Hedges' g=0.37) and maintenance (Hedges' g=0.34) effects on post-stroke aphasia. Additionally, ...

4. neurology.org neurology.org/doi/10.1212/WNL.0000000000213424

Transcranial Magnetic Stimulation Combined With ... This study provides Class III evidence that in patients with aphasia 6 or more months after a stroke, 1-Hz rTMS combined with intensive M-MAT improves WAB-AQ ...

5. pubs.asha.org pubs.asha.org/doi/abs/10.1044/2020_JSLHR-19-00077

Systematic Review and Meta-Analysis of Its Effect Upon ... The subgroup analyses of language performance showed positive effects of LF-rTMS among stroke patients with chronic aphasia and acute aphasia. LF-rTMS + SLT had ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3589757/

Transcranial Magnetic Stimulation and Aphasia Rehabilitation Given the extensive safety data and the strict adherence of our study protocol to current safety guidelines and recommendations endorsed by the ...

7. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1614586/full

Efficacy and safety of repetitive transcranial magnetic ... This study shows that rTMS can safely and effectively improve speech function in patients with post-stroke aphasia (PSA), particularly in auditory comprehension ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1052305721002585

Effect of High Frequency Transcranial Magnetic Stimulation ... Excitatory rTMS protocol appeared to be a safe modality, thus it should be further tested in blinded studies on larger sample size assessing its safety and ...