Personalized TMS for Stroke

Overseen By Sara J Hussain, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas at Austin

Must not be taking: Anti-epilepsy

Disqualifiers: Neurological disease, Pregnancy, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

37 Participants Needed

Trial Summary

What is the purpose of this trial?

Transcranial magnetic stimulation (TMS) interventions could feasibly strengthen residual corticospinal tract (CST) connections and enhance recovery of paretic hand function after stroke. This project will test whether personalized brain state-dependent TMS can activate the residual corticospinal tract better than standard TMS, and evaluate the relationship between this activation and hand motor impairment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes participants who have had recent changes to their medication use within the last month. This might suggest that stable medication use is preferred.

What data supports the effectiveness of the treatment Personalized TMS for Stroke?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can temporarily change brain activity after a stroke, which might help with rehabilitation, although the improvements in movement are usually small and not long-lasting. More studies are needed to confirm its effectiveness in routine care. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) generally safe for humans?

TMS is generally considered safe for humans, with the most serious risk being rare occurrences of seizures, especially when guidelines are not followed or in patients taking certain medications. Thousands of people, both healthy and with various conditions, have undergone TMS with minimal adverse effects when proper precautions are taken. ^{6 7 8 9 10}

How is personalized TMS treatment different from other stroke treatments?

Personalized TMS for stroke is unique because it uses brain state-dependent single-pulse TMS, which means the treatment is tailored to the individual's brain activity at the time of stimulation, potentially enhancing its effectiveness compared to standard repetitive TMS that does not adapt to real-time brain states. ^{1 2 4 5 11}

Eligibility Criteria

This trial is for individuals who have had a stroke and are experiencing hand function impairment. Participants should be able to undergo TMS treatments safely.

Inclusion Criteria

Ability to provide informed consent

My arm and hand movement is significantly limited.

I had a stroke more than 6 months ago.

Exclusion Criteria

I have changed my medications in the last month.

My arm and hand movements are near normal.

Presence of contraindications to transcranial magnetic stimulation (TMS) or peripheral nerve stimulation (PNS) including: cardiac pacemaker, cochlear implant, cortical stimulator, deep brain stimulator, vagus nerve stimulator, cervical spine epidural stimulator, and/or ventriculoperitoneal shunt, ferromagnetic metallic implants above the level of the seventh cervical vertebrae, seizure in the last 12 months while taking anti-epilepsy medication, history of adverse reactions to TMS or PNS

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Testing and Assessment

Participants undergo testing for consent capacity, motor impairment assessment, and screening for residual corticospinal connections.

1 day

1 visit (in-person)

TMS Intervention

Participants receive personalized brain state-dependent TMS and random state TMS to assess corticospinal tract activation.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after TMS intervention

1 week

Treatment Details

Interventions

• Personalized brain state-dependent single-pulse TMS

Trial Overview The study is testing if personalized brain state-dependent TMS can better activate the corticospinal tract, which may improve hand movement after a stroke, compared to standard TMS.

Participant Groups

Group I: Brain state-dependent TMS during strong states Experimental Treatment 1 Intervention

Group II: Brain state-dependent TMS during random states Active Control 1 Intervention

Personalized brain state-dependent single-pulse TMS is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Stroke rehabilitation
• Depression
• Migraines

Approved in European Union as Transcranial Magnetic Stimulation for:

• Stroke rehabilitation
• Depression
• Chronic pain

Approved in Canada as Repetitive Transcranial Magnetic Stimulation for:

• Stroke rehabilitation
• Major depressive disorder

Who Is Running the Clinical Trial?

University of Texas at Austin

Lead Sponsor

Trials

387

Recruited

86,100+

Findings from Research

Transcranial magnetic stimulation (TMS) has shown promise in predicting recovery of motor function after stroke, especially when combined with other assessment tools like clinical evaluations and MRI, although it cannot predict recovery on its own.

Repetitive TMS (rTMS) can temporarily modify motor cortex excitability to aid rehabilitation, but studies show only modest improvements in motor function, particularly in the acute or sub-acute stages after stroke, indicating that more research is needed before routine clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) in stroke: Ready for clinical practice? Smith, MC., Stinear, CM.[2022]

In a study of 103 stroke patients, paired-pulse transcranial magnetic stimulation revealed that the unaffected hemisphere showed increased intracortical inhibition (ICI) during the acute phase in mild-to-moderate stroke, indicating a shift in excitability patterns.

As stroke progressed to the subacute stage, the affected hemisphere became more disinhibited, suggesting that understanding these changes can help guide neuromodulation therapies for stroke recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in Intracortical Excitability of Affected and Unaffected Hemispheres After Stroke Evaluated by Paired-Pulse Transcranial Magnetic Stimulation. Seo, HY., Kim, GW., Won, YH., et al.[2020]

Transcranial magnetic stimulation (TMS) can successfully evoke potentials (TEPs) in chronic stroke survivors using lower stimulus intensities, making it a more accessible method for assessing motor function compared to traditional motor evoked potentials.

The study found that TEPs showed significant differences between stroke survivors and healthy adults, particularly with a larger P30 amplitude in stroke participants, indicating that TEPs could serve as a useful biomarker for evaluating upper-limb motor function post-stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation-EEG Biomarkers of Poststroke Upper-Limb Motor Function. Hordacre, B., Ghosh, R., Goldsworthy, MR., et al.[2020]

Transcranial magnetic stimulation (TMS) showed moderate to excellent inter-rater reliability in assessing motor thresholds in 31 hospitalized acute ischemic stroke patients, indicating it can be a reliable tool for evaluating neurophysiology in this population.

The study found that improvements in TMS measurements of less than 4.96 to 12.51 may be due to measurement error rather than true changes, highlighting the importance of understanding the limits of TMS in clinical assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Test-Retest Reliability and Agreement of Single Pulse Transcranial Magnetic Stimulation (TMS) for Measuring Activity in Motor Cortex in Patients With Acute Ischemic Stroke. Henriette, B., Marianne, N., Rønne, PJ., et al.[2023]

In a study involving 8 stroke patients and 5 healthy controls, the optimal interstimulus interval (ISI) for paired pulse TMS to evoke motor responses in the upper extremity was found to be 25-40 ms, indicating a specific timing that enhances muscle activation.

Stroke patients showed similar optimal ISI ranges for the non-lesioned hemisphere as healthy controls, but the lesioned hemisphere required a longer ISI (12-50 ms) to achieve effective stimulation, highlighting differences in motor response mechanisms post-stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using paired pulse TMS to facilitate contralateral and ipsilateral MEPs in upper extremity muscles of chronic hemiparetic stroke patients. Schwerin, SC., Yao, J., Dewald, JP.[2021]

Transcranial magnetic stimulation (TMS) has a strong safety record, with seizures being an extremely rare adverse effect, particularly in patients receiving repetitive TMS (rTMS) under certain conditions.

The updated guidelines provide comprehensive safety recommendations for TMS applications, including risk assessments for new stimulation paradigms and precautions for use in patients with implanted devices or in neuroimaging settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Rossi, S., Hallett, M., Rossini, PM., et al.[2022]

Transcranial magnetic stimulation (TMS) has a very low seizure risk, with only 0.08 seizures reported per 1,000 sessions, and less than 0.02 seizures per 1,000 sessions when guidelines are followed for individuals without known risk factors.

The study found that exceeding safety guidelines increases the risk of seizures, and seizures are more likely to occur during the first few TMS sessions, suggesting that TMS is generally safe when administered properly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. Lerner, AJ., Wassermann, EM., Tamir, DI.[2021]

A review of 84 single pulse and paired-pulse TMS studies with 1091 Parkinson's disease patients, and 77 repetitive TMS studies with 1137 patients, found a very low risk of adverse events, with no seizures reported.

The overall risk of adverse events from rTMS was 0.040 per patient, with common side effects being mild and transient, such as headaches and scalp pain, indicating that TMS is generally safe for Parkinson's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial magnetic stimulation in Parkinson's disease: a review of the literature. Vonloh, M., Chen, R., Kluger, B.[2021]

The consensus conference updated safety guidelines for transcranial magnetic stimulation (TMS), confirming that the risk of inducing seizures is low, even in patients on central nervous system medications, when using traditional stimulation parameters.

New safety issues were addressed, including the responsibilities of device manufacturers and the safety of novel TMS applications, ensuring that updated operational guidelines are in place for future research and clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Rossi, S., Antal, A., Bestmann, S., et al.[2023]

Transcranial magnetic stimulation (TMS) is safe to use with implanted deep brain stimulation (DBS) devices at low to moderate intensities, as no movement or temperature increase was observed during stimulation at 0.2 Hz with 100% intensity for 1 hour.

However, caution is advised when using high-intensity TMS (over 50%) near looped DBS leads, as it can exceed the safety limit for charge density, potentially leading to electrical tissue injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of transcranial magnetic stimulation with deep brain stimulation instruments. Shimojima, Y., Morita, H., Nishikawa, N., et al.[2010]

The TMS Synchronized Exoskeleton Feedback (TSEF) platform, which combines real-time feedback from exoskeleton movements and brain stimulation, showed promising results in enhancing cortical excitability in stroke patients, with a significant increase in Motor Evoked Potential and improvement in clinical scales after 20 sessions.

In a proof-of-concept study involving three patients, the TSEF platform demonstrated clinical gains that were not observed in a control group receiving standard physiotherapy, suggesting that personalized brain stimulation may enhance rehabilitation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualized closed-loop TMS synchronized with exoskeleton for modulation of cortical-excitability in patients with stroke: a proof-of-concept study. Singh, N., Saini, M., Kumar, N., et al.[2023]

References

1. Scotland pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) in stroke: Ready for clinical practice? [2022]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Changes in Intracortical Excitability of Affected and Unaffected Hemispheres After Stroke Evaluated by Paired-Pulse Transcranial Magnetic Stimulation. [2020]

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

Transcranial Magnetic Stimulation-EEG Biomarkers of Poststroke Upper-Limb Motor Function. [2020]

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

Test-Retest Reliability and Agreement of Single Pulse Transcranial Magnetic Stimulation (TMS) for Measuring Activity in Motor Cortex in Patients With Acute Ischemic Stroke. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Using paired pulse TMS to facilitate contralateral and ipsilateral MEPs in upper extremity muscles of chronic hemiparetic stroke patients. [2021]

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

Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. [2022]

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

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Safety of transcranial magnetic stimulation in Parkinson's disease: a review of the literature. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. [2023]

10. England pubmed.ncbi.nlm.nih.gov

The safety of transcranial magnetic stimulation with deep brain stimulation instruments. [2010]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Individualized closed-loop TMS synchronized with exoskeleton for modulation of cortical-excitability in patients with stroke: a proof-of-concept study. [2023]