Transcranial Magnetic Stimulation for Stroke

(CAM Trial)

Overseen By Amy Boos

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Serious illness, Orthopedic problems, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate (within 2 s after stimulation)

76 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Transcranial Magnetic Stimulation (TMS), a treatment using magnetic fields, affects brain areas responsible for movement after a stroke. Participants will perform reaching movements with a robotic arm while receiving TMS to observe its influence on movement control. The trial seeks individuals who had a stroke at least six months ago, resulting in mild to moderate arm issues, and who are otherwise medically stable.

As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance stroke recovery treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study coordinators for more details.

What prior data suggests that Transcranial Magnetic Stimulation is safe for use with a robotic arm device?

Research shows that Transcranial Magnetic Stimulation (TMS) is safe for most people. Studies indicate that it is usually well-tolerated and not painful. Some people might experience mild side effects, but serious issues are rare. Researchers are studying TMS to help people regain movement after a stroke. It has been used in other treatments, providing a wealth of safety information. For those considering joining a trial, TMS appears to be a safe option based on current research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Transcranial Magnetic Stimulation (TMS) is unique because it offers a non-invasive way to potentially enhance recovery after a stroke. Unlike traditional rehabilitation methods like physical therapy and medication, which focus more on physical movement and managing symptoms, TMS uses magnetic fields to stimulate nerve cells in the brain. This approach aims to directly influence brain plasticity, which could improve motor function more effectively. Researchers are excited about TMS because it targets the brain's ability to rewire itself, offering hope for faster and more robust recovery outcomes.

What evidence suggests that Transcranial Magnetic Stimulation is effective for stroke?

Research has shown that Transcranial Magnetic Stimulation (TMS), which participants in this trial will receive, can improve movement after a stroke. Studies have found that TMS enhances motor skills and reduces difficulties in stroke patients. A review of several studies found that TMS significantly improved arm and hand movement, both in the short term and long term. Additionally, it assists with swallowing and thinking skills after a stroke. Overall, TMS appears promising as a tool for aiding stroke survivors in recovery. ^{1 2 3 6 7}

Who Is on the Research Team?

George F Wittenberg, MD PhD

Principal Investigator

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 45-90 who've had a stroke at least 6 months ago, resulting in mild to moderate arm dysfunction. They must be medically stable and have no serious illnesses that would affect participation. People with visual loss, joint motion issues, or conditions preventing safe TMS/MRI use cannot join.

Inclusion Criteria

I am between 45 and 90 years old.

I had a stroke more than 6 months ago.

I had a stroke in a deep part of my brain.

Exclusion Criteria

Unable to comply with requirements of the study

I do not have a serious illness that would stop me from joining.

You have a medical condition or implant that makes it unsafe for you to have TMS or MRI.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Transcranial Magnetic Stimulation (TMS) while performing reaching movements in a robotic system

Immediate (within 2 s after stimulation)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transcranial Magnetic Stimulation

Trial Overview

The study uses Transcranial Magnetic Stimulation (TMS) while participants make movements with a robotic arm device to understand how the brain controls movement before and after a stroke and when it's most responsive to TMS.

How Is the Trial Designed?

Group I: Reaching with TMS Experimental Treatment 1 Intervention

All participants enrolled in this group will receive TMS while performing reaching movements in a robotic system.

Transcranial Magnetic Stimulation is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder

Approved in Canada as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Approved in European Union as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

VA Pittsburgh Healthcare System

Collaborator

Trials

36

Recruited

15,900+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

Published Research Related to This Trial

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]

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]

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) has shown significant benefits for various motor and cognitive functions in stroke recovery, based on a systematic review of 57 studies involving 2595 patients.

Despite these positive findings, the variability in reported effect sizes suggests a need for larger, well-designed trials that collect detailed patient data to better understand the mechanisms of action and improve treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence of rTMS for Motor or Cognitive Stroke Recovery: Hype or Hope? Hofmeijer, J., Ham, F., Kwakkel, G.[2023]

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 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]

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]

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]

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) has not been thoroughly studied for side effects, with the main known risk being the acute production of seizures.

While tissue damage from rTMS is unlikely, there are concerns about potential cognitive effects and the possibility of long-term changes in brain function that have not yet been fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of repetitive transcranial magnetic stimulation. Wassermann, EM.[2005]

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]

Citations

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pmc.ncbi.nlm.nih.gov

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Repetitive transcranial magnetic stimulation for stroke ...

In this review, the clinical benefits of rTMS for stroke rehabilitation are summarized, including improvements of motor impairment, dysphagia, ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6763938/

Repetitive transcranial magnetic stimulation in stroke ...

A meta-analysis of studies using LF-rTMS, HF-rTMS, and TBS for the recovery of the upper limb found a significant short- and long-term improvement in the ...

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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, ...

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1094715924006652

Repetitive Transcranial Magnetic Stimulation for Motor ...

Among the secondary outcome measures, only mRS was significantly improved in the rTMS group after intervention (MD = −0.5, p = 0.013) and at the last follow-up ...

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eurjmedres.biomedcentral.com

eurjmedres.biomedcentral.com/articles/10.1186/s40001-025-02714-0

Research on transcranial magnetic stimulation for stroke ...

Numerous studies have confirmed that TMS is effective for addressing motor dysfunction, swallowing disorders, cognitive impairment, and ...

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frontiersin.org

frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1197422/full

Repetitive transcranial magnetic stimulation for stroke ...

rTMS have been shown to promote effectively rehabilitation of neurological sequelae post-stroke, including motor impairment, dysphagia, cognitive impairment, ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9542838/

Effectiveness and safety of repetitive transcranial magnetic ...

This protocol aims to evaluate the clinical effect and safety of rTMS on PSMD by analyzing results from randomized controlled trials.