Transcranial Magnetic Stimulation for Stroke

(REALISE Trial)

Overseen By Wuwei Feng, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Must not be taking: Dementia drugs

Disqualifiers: Bilateral strokes, Neuromuscular disorders, Uncontrolled hypertension, others

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

Compensation: Varies

Number of Visits: 3

Duration: 3 sessions

26 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a technique called repetitive Transcranial Magnetic Stimulation (rTMS) to improve hand function in stroke survivors. The goal is to determine if this non-invasive brain stimulation can facilitate hand use. Participants will receive various types of brain stimulation to identify the most effective method. This trial suits individuals who experienced their first stroke at least six months ago, resulting in noticeable weakness in one arm. As an unphased trial, it offers participants the chance to contribute to pioneering research that could enhance recovery options for stroke survivors.

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 does exclude people taking certain dementia drugs. It's best to discuss your specific medications with the trial team.

What prior data suggests that this brain stimulation technique is safe for stroke patients?

Research has shown that rTMS (Repetitive Transcranial Magnetic Stimulation) is generally safe and well-tolerated. Most patients find it painless, with only a few experiencing discomfort. Even high-dose versions of rTMS are considered safe. This treatment is non-invasive, meaning it doesn't involve surgery or entering the body. Most individuals who have used rTMS for stroke recovery have not experienced serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about transcranial magnetic stimulation (rTMS) for stroke recovery because it offers a non-invasive way to stimulate brain regions involved in movement. Unlike standard stroke treatments, which might include physical therapy or medications, rTMS uses magnetic fields to activate nerve cells in the brain, potentially enhancing motor function. This approach could lead to faster and more significant improvements in motor recovery compared to traditional methods. The trial explores different intensities and focal points of stimulation, aiming to optimize the technique for better patient outcomes.

What evidence suggests that rTMS is effective for improving hand function after a stroke?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can help stroke patients improve their movement abilities. In this trial, participants will undergo three non-invasive brain stimulation modalities: focal conventional iTBS, focal high-dose iTBS, and diffuse high-dose iTBS. Studies have found that rTMS can significantly enhance arm and hand movement in stroke recovery. This method uses magnetic fields to stimulate specific brain areas, aiding movement restoration. Evidence suggests that rTMS supports both short-term and long-term recovery of arm and hand function. Overall, it is considered a promising non-invasive option for helping stroke survivors regain use of their hands and arms. ^{1 2 6 7 8}

Who Is on the Research Team?

Wayne Feng, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for individuals who have experienced a stroke and are facing challenges with hand muscle function. The study aims to help these patients improve the use of their hands.

Inclusion Criteria

I am 21 years old or older.

I had my first stroke, confirmed by brain scans, more than 6 months ago.

Inducible rest motor threshold and testing motor threshold recorded from the affected first dorsal interosseous (FDI) muscle from the study subject

Exclusion Criteria

Other co-existent neuromuscular disorders affecting upper extremity motor impairment

My high blood pressure is not controlled by medication.

Presence of any MRI/rTMS risk factors including but not limited to: an electrically, magnetically, or mechanically activated metallic or nonmetallic implant including cardiac pacemaker, intracerebral vascular clips or any other electrically sensitive support system; a non-fixed metallic part in any part of the body, including a previous metallic injury to the eye; history of seizure disorder before stroke or seizure after stroke; preexisting scalp lesion or bone defect or hemicraniectomy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo three non-invasive brain stimulation modalities using iTBS protocols to improve motor recovery

3 sessions

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• rTMS

Trial Overview

The intervention being studied is rTMS (Repetitive Transcranial Magnetic Stimulation), which is a non-invasive brain stimulation technique that may aid in the rehabilitation of hand muscles in chronic stroke patients.

How Is the Trial Designed?

Group I: Non-invasive Brain Stimulation Modalities Experimental Treatment 1 Intervention

All participants will undergo three non-invasive brain stimulation modalities: 1. Focal conventional iTBS over the ipsilesional motor cortex (i.e., a single bout of 600 pulses over a single spot; FiTBS600). 2. Focal high dose iTBS over the ipsilesional motor cortex (i.e. 4 bouts of 600 pulses over a single spot = 2400 pulses; FiTBS2400). 3. Diffuse high dose iTBS over the ipsilesional motor cortex (i.e. 4 bouts of 600 pulses over 4 spots: 600 pulses/spot × 4 spots = 2400 pulses; DiTBS2400)

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

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]

The study found that contralesional repetitive transcranial magnetic stimulation (rTMS) was safe and well-tolerated in 10 chronic stroke patients, with no adverse effects like seizures or worsening motor function, indicating its potential as a noninvasive treatment option.

There was a positive relationship between the integrity of transcallosal motor fibers and motor improvement after rTMS, suggesting that rTMS may enhance neuroplasticity in the brain, which could be useful for rehabilitation in severe chronic stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effects of contralesional rTMS in severe stroke: safety, cortical excitability, and relationship with transcallosal motor fibers. Demirtas-Tatlidede, A., Alonso-Alonso, M., Shetty, RP., et al.[2018]

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]

Repetitive transcranial magnetic stimulation (rTMS) can enhance brain plasticity and has shown promise in improving motor recovery when applied in the early weeks following a stroke, as opposed to months or years later.

Clinical studies indicate that early rTMS treatment can lead to sustained improvements in grip strength and upper extremity motor function, suggesting its potential as a beneficial intervention shortly after a stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for Upper Extremity Motor Recovery: Does It Help? Schambra, HM.[2020]

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]

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 patient with treatment-resistant depression (TRD) showed unexpected improvement after experiencing a seizure during repetitive transcranial magnetic stimulation (rTMS), suggesting a potential link between seizure activity and therapeutic effects in TRD.

While rTMS is generally safe, known adverse events include headaches and seizures; this case highlights an unusual outcome where a seizure may have contributed to the patient's improvement, warranting further investigation into the mechanisms of rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. Kim, JW., Bae, KY., Kim, SW., et al.[2020]

Repetitive transcranial magnetic stimulation (rTMS) is generally a well-tolerated treatment for depression, with mild side effects like headaches being the most common, while severe adverse effects are rare.

Special precautions are necessary for certain groups, such as adolescents, pregnant women, and individuals with metal implants, but with proper assessment and monitoring, rTMS can be safely administered to many patients with depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. Taylor, R., Galvez, V., Loo, C.[2019]

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 chronic stroke patient, 5 days of low-frequency rTMS on the intact motor cortex led to improvements in motor function and neuropsychological symptoms without any adverse effects.

Neuroimaging revealed that these improvements were linked to changes in brain activity, specifically a reduction in hyperactivity and reorganization in the opposite hemisphere, suggesting a mechanism of neuroplasticity that supports recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral and neuroplastic effects of low-frequency rTMS of the unaffected hemisphere in a chronic stroke patient: a concomitant TMS and fMRI study. Salatino, A., Berra, E., Troni, W., et al.[2014]

In a pilot study involving 8 post-stroke patients, both inhibitory and facilitatory settings of repetitive transcranial magnetic stimulation (rTMS) showed large effect sizes in improving motor evoked potentials (MEP) on both the affected and unaffected sides of the body.

The study found no reported side effects from rTMS, indicating that it is a safe intervention for enhancing motor recovery in stroke patients, warranting further research with a larger sample size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical Modulation After Two Different Repetitive Transcranial Magnetic Stimulation Protocols in Similar Ischemic Stroke Patients. Hanafi, MH., Kassim, NK., Ibrahim, AH., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

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) 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]

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