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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to use Transcranial Magnetic Stimulation (TMS) while subjects are making reaching movements in a robotic arm device in order to discover how different brain areas control movement before and after stroke and when these brain areas are most sensitive to TMS.

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.

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

Transcranial magnetic stimulation (TMS), including repetitive TMS (rTMS), has been studied for safety in both healthy individuals and those with various conditions. While it is generally considered safe, there have been reports of seizures and other adverse effects, so guidelines have been developed to minimize risks. Safety guidelines have been updated over the years, with the most recent in 2021, to ensure safe application in clinical settings. ^{1 2 3 4 5}

How is the treatment Transcranial Magnetic Stimulation (rTMS) unique for stroke recovery?

Transcranial Magnetic Stimulation (rTMS) is unique because it is a non-invasive treatment that uses magnetic fields to stimulate nerve cells in the brain, which can help improve motor function and recovery after a stroke. Unlike traditional therapies, rTMS can target specific brain areas to restore balance between brain hemispheres, potentially leading to sustained improvements in motor skills. ^{1 6 7 8 9}

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation for stroke recovery?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can help improve motor function and reduce disability after a stroke by balancing brain activity between the two sides of the brain. Studies have found that rTMS can aid in the recovery of lower limb function and enhance overall motor recovery in stroke patients. ^{6 10 11 12 13}

Research Team

George F Wittenberg, MD PhD

Principal Investigator

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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) 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]

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) 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) 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]

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]

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]

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 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]

References

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

Evidence of rTMS for Motor or Cognitive Stroke Recovery: Hype or Hope? [2023]

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. 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]

4. 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]

5. 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]

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

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

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

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

8. 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]

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

Side effects of repetitive transcranial magnetic stimulation. [2005]

10. Netherlands pubmed.ncbi.nlm.nih.gov

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

11. 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]

12. Malaysia pubmed.ncbi.nlm.nih.gov

Cortical Modulation After Two Different Repetitive Transcranial Magnetic Stimulation Protocols in Similar Ischemic Stroke Patients. [2022]

13. 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]