TMS for Stroke

Overseen by Alexander Opitz, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Minnesota

Disqualifiers: Metal implant, Botulinum toxin, Pregnancy, Seizure, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is studying how using magnetic pulses can help improve movement in people who have had a stroke. The study aims to find the best way to use these pulses by looking at brain activity patterns during treatment. Magnetic pulses have been used in several medical and clinical research applications, including stroke 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. However, if you have had upper extremity botulinum toxin treatment in the last 6 months, you cannot participate.

What data supports the effectiveness of the treatment TMS for stroke?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can help improve motor function in stroke patients, particularly in the lower limbs, and may also aid in overall motor recovery after a stroke. ^{1 2 3 4 5}

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

Transcranial magnetic stimulation (TMS) is generally considered safe, but there is a slight risk of seizures and other adverse events. Most studies, including those on conditions like depression and obesity, report a reassuring safety profile with proper guidelines and monitoring. ^{6 7 8 9 10}

How is the treatment TMS for stroke different from other treatments?

Transcranial Magnetic Stimulation (TMS) is unique because it is a non-invasive technique that uses magnetic fields to stimulate nerve cells in the brain, which can help improve motor function and neuroplasticity (the brain's ability to reorganize itself) after a stroke. Unlike traditional physical therapies, TMS directly targets brain activity to promote recovery. ^{11 12 13 14 15}

Research Team

Alexander Opitz, PhD

Principal Investigator

University of Minnesota Department of Biomedical Engineering

Eligibility Criteria

This trial is for individuals who have experienced a stroke over 6 months ago and are facing motor difficulties. Participants must be able to communicate in English. Those with metal or electric implants, recent botulinum toxin treatments in the upper extremities, current pregnancy or breastfeeding, or a history of seizures cannot join.

Inclusion Criteria

I have had a stroke over 6 months ago and still experience movement problems.

Confident level of English language

Exclusion Criteria

I have had a seizure without a known cause.

Pregnancy or breastfeeding

You have a metal or electric implant in your head, neck, or chest.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Assessment

Assessment of stroke characteristics and MRI scan for participants with stroke; confirmation of lack of unilateral stroke for participants without stroke

1 day

1 visit (in-person)

TMS Experiment

Main transcranial magnetic stimulation experiment to measure motor evoked potentials (MEPs) and study phase-dependent cortical excitability

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after TMS treatment

2-4 weeks

Treatment Details

Interventions

• TMS (Procedure)

Trial Overview The study is examining how transcranial magnetic stimulation (TMS) affects the excitability of the motor cortex in stroke survivors. It specifically looks at how different phases of brain wave rhythms influence this excitability.

Participant Groups

Group I: Participants Without Unilateral Stroke Experimental Treatment 1 Intervention

Participants without self-reported unilateral stroke will take part in two experimental sessions: First, for assessment of stroke characteristics, and second, the main transcranial magnetic stimulation experiment. During the first experimental session, the lack of unilateral stroke will be confirmed. In participants without stroke, TMS will be applied targeting at the intensity of up to 120% resting motor threshold both left and right hemisphere.

Group II: Participants With Unilateral Stroke Experimental Treatment 1 Intervention

Participants with self-reported unilateral stroke will take part in two experimental sessions: First, for assessment of stroke characteristics and MRI scan, and second, the main transcranial magnetic stimulation experiment. During the first experimental session, the unilateral stroke will be confirmed. In participants with stroke, TMS will be applied over the motor cortex on the affected and non-affected hemisphere at the intensity of up to 120% resting motor threshold.

TMS is already approved in Canada for the following indications:

Approved in Canada as Transcranial Magnetic Stimulation for:

• Depression
• Anxiety disorders
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Shashank Priya

University of Minnesota

Chief Executive Officer since 2023

PhD in Materials Engineering from Penn State

Charles Semba

University of Minnesota

Chief Medical Officer since 2021

MD from the University of Minnesota Medical School

Findings from Research

Repetitive transcranial magnetic stimulation (rTMS) significantly improves lower limb motor function in stroke patients, with a standardized mean difference of 0.66 for body function and activity, based on a meta-analysis of 8 studies involving 169 participants.

The treatment is considered safe, with only one study reporting mild adverse effects, indicating that rTMS could be a beneficial short-term therapy for enhancing recovery after a stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation of lower limb motor function in patients with stroke: a systematic review and meta-analysis of randomized controlled trials. Tung, YC., Lai, CH., Liao, CD., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) showed significant improvements in balance and mobility in stroke patients, based on a review of 15 trials involving 385 participants.

Despite these positive effects, rTMS did not demonstrate significant immediate improvements in lower limb function as measured by the Fugl-Meyer Assessment, indicating that while it may help with mobility and balance, its effectiveness for overall lower limb recovery remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for the Treatment of Lower Limb Dysfunction in Patients Poststroke: A Systematic Review with Meta-Analysis. Ghayour-Najafabadi, M., Memari, AH., Hosseini, L., et al.[2020]

In a study of 41 patients with poststroke cognitive impairment, both 5 Hz rTMS and intermittent theta burst stimulation (iTBS) showed significant improvements in cognitive function compared to sham stimulation, particularly in attention and memory.

The 5 Hz rTMS protocol was especially effective in enhancing attention, suggesting it may play a crucial role in slowing cognitive decline and promoting neuroplasticity after a stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-frequency versus theta burst transcranial magnetic stimulation for the treatment of poststroke cognitive impairment in humans Tsai, PY., Lin, WS., Tsai, KT., et al.[2021]

In a pilot study involving 60 patients with ischemic stroke, both 5-Hz stimulation of the lesioned hemisphere and 1-Hz inhibition of the contra-lesional hemisphere using rTMS significantly improved motor function, as measured by various clinical assessments over 12 weeks.

The improvements in motor recovery were sustained without any significant adverse events, supporting the idea that rTMS can effectively aid rehabilitation in stroke patients by restoring balance between the brain's hemispheres.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation at 1Hz and 5Hz produces sustained improvement in motor function and disability after ischaemic stroke. Emara, TH., Moustafa, RR., ElNahas, NM., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) significantly improved motor function in stroke patients within the first month after treatment, particularly in upper limb function, as shown by various motor functional scores assessed over time.

The benefits of rTMS on upper extremity function were observed to last for up to one year, indicating its potential as a long-term therapeutic intervention for motor recovery after stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of repetitive transcranial magnetic stimulation (rTMS) after acute stroke: A one-year longitudinal randomized trial. Guan, YZ., Li, J., Zhang, XW., et al.[2021]

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]

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool that can effectively treat clinical depression and potentially other brain disorders, but it carries risks, including the potential to induce seizures, as evidenced by 7 known cases by 1996.

A workshop established safety guidelines for rTMS, emphasizing the importance of monitoring, ethical considerations, and the expertise required for its administration to minimize risks and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Wassermann, EM.[2022]

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 18 subjects with major depression, repetitive transcranial magnetic stimulation (rTMS) for up to 4 weeks was found to be generally safe, with no significant mean deficits in neuropsychologic function or auditory thresholds.

However, two patients experienced mild high-frequency hearing loss, indicating that while rTMS is safe for most, individual responses may vary and warrant further investigation into long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients. Loo, C., Sachdev, P., Elsayed, H., et al.[2019]

In a study of 63 obese individuals undergoing a 5-week rTMS treatment for weight control, the treatment showed a reassuring safety profile with no unexpected adverse events reported up to one year after treatment.

The most common side effects were moderate headaches (40.4%) and local pain/discomfort (19.2%), particularly more frequent in the high-frequency rTMS group, but overall, rTMS was well tolerated in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of repeated sessions of deep transcranial magnetic stimulation in obesity. Ferrulli, A., Massarini, S., Macrì, C., et al.[2021]

In a study involving 60 stroke patients, combining low-frequency repetitive transcranial magnetic stimulation (rTMS) with functional electrical stimulation (FES) significantly improved hand function compared to either treatment alone.

The combination therapy led to better scores in the Fugl-Meyer assessment and total active movement of fingers, indicating enhanced recovery of hand functions such as grasping and pinching.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of repetitive transcranial magnetic stimulation combined with functional electrical stimulation on hand function of stroke: A randomized controlled trial. Yang, Z., Qiao, L., He, J., et al.[2022]

In a study involving 20 patients in the subacute phase of stroke, high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) combined with a rehabilitation program (RP) significantly improved upper limb function, particularly in box and block test performance and grip strength compared to the control group.

HF-rTMS appears to be a safe and effective treatment option for enhancing recovery in hemiparesis patients after stroke, suggesting its potential as a practical rehabilitation modality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of High-Frequency Repetitive Transcranial Magnetic Stimulation on Functional Indices of Affected Upper Limb in Patients with Subacute Stroke. Moslemi Haghighi, F., Kordi Yoosefinejad, A., Razeghi, M., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) shows variable effects on corticospinal pathway excitability in healthy adults, with different frequencies producing different outcomes, indicating that the optimal parameters for rTMS are not yet established.

In stroke patients, there is a trend suggesting that 10 sessions of 3 Hz rTMS may aid in the recovery of motor-evoked potentials, but overall evidence is insufficient to determine effective dosing for improving motor function in paretic limbs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Informing dose-finding studies of repetitive transcranial magnetic stimulation to enhance motor function: a qualitative systematic review. Hiscock, A., Miller, S., Rothwell, J., et al.[2018]

Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective therapy for post-stroke rehabilitation, enhancing neuroplasticity and helping patients recover motor skills and cognitive functions.

rTMS can optimize brain activity by applying targeted electromagnetic pulses to specific brain regions, leading to improvements in various stroke-related complications such as motor disorders, aphasia, and depression, although more extensive clinical trials are needed for broader recommendations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current evidence on transcranial magnetic stimulation and its potential usefulness in post-stroke neurorehabilitation: Opening new doors to the treatment of cerebrovascular disease. León Ruiz, M., Rodríguez Sarasa, ML., Sanjuán Rodríguez, L., et al.[2022]

High-frequency rTMS (20 and 25 Hz) applied to the motor cortex of chronic stroke patients may increase the risk of seizures, as indicated by EMG bursts and muscle excitation observed during the study.

Despite the safety concerns, the study found no significant increase in motor cortex excitability or improvement in hand strength after rTMS, suggesting that the stimulation parameters used may not be effective for rehabilitation in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety study of high-frequency transcranial magnetic stimulation in patients with chronic stroke. Lomarev, MP., Kim, DY., Richardson, SP., et al.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation of lower limb motor function in patients with stroke: a systematic review and meta-analysis of randomized controlled trials. [2022]

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

Repetitive Transcranial Magnetic Stimulation for the Treatment of Lower Limb Dysfunction in Patients Poststroke: A Systematic Review with Meta-Analysis. [2020]

3. Canada pubmed.ncbi.nlm.nih.gov

High-frequency versus theta burst transcranial magnetic stimulation for the treatment of poststroke cognitive impairment in humans [2021]

4. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation at 1Hz and 5Hz produces sustained improvement in motor function and disability after ischaemic stroke. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Effectiveness of repetitive transcranial magnetic stimulation (rTMS) after acute stroke: A one-year longitudinal randomized trial. [2021]

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

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

7. Ireland pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. [2022]

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

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

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

Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients. [2019]

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

Safety and tolerability of repeated sessions of deep transcranial magnetic stimulation in obesity. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of repetitive transcranial magnetic stimulation combined with functional electrical stimulation on hand function of stroke: A randomized controlled trial. [2022]

12. Iran pubmed.ncbi.nlm.nih.gov

The Effect of High-Frequency Repetitive Transcranial Magnetic Stimulation on Functional Indices of Affected Upper Limb in Patients with Subacute Stroke. [2022]

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

Informing dose-finding studies of repetitive transcranial magnetic stimulation to enhance motor function: a qualitative systematic review. [2018]

14. Spain pubmed.ncbi.nlm.nih.gov

Current evidence on transcranial magnetic stimulation and its potential usefulness in post-stroke neurorehabilitation: Opening new doors to the treatment of cerebrovascular disease. [2022]

15. Netherlands pubmed.ncbi.nlm.nih.gov

Safety study of high-frequency transcranial magnetic stimulation in patients with chronic stroke. [2016]