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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a special type of brain stimulation, called personalized TMS (Transcranial Magnetic Stimulation), can improve hand movement in stroke survivors. Researchers seek to discover if using TMS at specific brain states is more effective than standard TMS. They are looking for individuals who experienced a stroke over six months ago and still have some upper limb weakness. Participants must be willing to join and able to give consent. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance stroke recovery treatments.

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 prior data suggests that personalized brain state-dependent TMS is safe for stroke patients?

Research shows that personalized brain state-dependent transcranial magnetic stimulation (TMS) is generally well-tolerated. Past studies found that repetitive TMS improves motor skills and is well-received by patients with treatment-resistant depression and other mental health disorders. These studies reported no major safety issues, suggesting that this TMS method is safe. While researchers are still collecting specific safety data for personalized single-pulse TMS in stroke patients, the use of TMS in other conditions offers some reassurance about its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about personalized brain state-dependent single-pulse Transcranial Magnetic Stimulation (TMS) for stroke recovery because it offers a tailored approach, unlike traditional stroke treatments that typically involve medications or physical therapy. This method uniquely adapts to the patient's brain activity, potentially enhancing the brain's natural recovery process. By delivering TMS during specific brain states, this technique aims to improve motor function more effectively than random or untargeted applications. This innovative approach could lead to more efficient and personalized rehabilitation for stroke patients.

What evidence suggests that this trial's treatments could be effective for stroke recovery?

This trial will compare two approaches of personalized brain state-dependent TMS (transcranial magnetic stimulation) for stroke recovery. Research has shown that this technique may improve hand function after a stroke by targeting specific brain activity patterns and activating the brain's movement pathways more effectively than standard TMS. One small study found that matching TMS with brain waves improved movement and reduced disability. Another study demonstrated that whole-brain EEG patterns can predict TMS effectiveness in real-time. These findings suggest that personalized TMS could be a helpful tool for stroke recovery. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

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

My arm and hand movements are near normal.

I have changed my medications in the last month.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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) 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]

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]

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]

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]

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) 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06533176

Real-time Personalized Brain State-dependent TMS After ... This project will test whether personalized brain state-dependent TMS can activate the residual corticospinal tract better than standard TMS.

2. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.123.043159

Evidence of rTMS for Motor or Cognitive Stroke Recovery CONCLUSIONS: Repetitive transcranial magnetic stimulation holds the potential to benefit a range of motor and cognitive outcomes after stroke, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11381265/

Brain state-dependent repetitive transcranial magnetic ... This pilot study demonstrated that the brain oscillation-synchronized rTMS protocol produced beneficial effects on motor impairment, motor function and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X24013925

Personalized whole-brain activity patterns predict human ... Our results show for the first time that personalized whole-brain EEG activity patterns predict CST activation in real-time in healthy humans.

5. medrxiv.org medrxiv.org/content/10.1101/2024.03.10.24304040v1.full

A Proof of Concept Randomized Controlled Trial This study demonstrates that brain state-dependent stimulation can be successfully applied in chronic stroke patients with clinical effects that ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2451902222002671

Personalized Repetitive Transcranial Magnetic Stimulation ... rTMS is well tolerated and clinically effective for treatment-resistant depression and other neuropsychiatric disorders.

7. biorxiv.org biorxiv.org/content/10.1101/2024.08.15.607985v1.full-text

Personalized whole-brain activity patterns predict human ... These findings represent a pivotal step towards using personalized brain state-dependent TMS interventions to promote poststroke CST function.