Transcranial Magnetic Stimulation for Spinal Cord Injury

(uMEP Trial)

Overseen By Blair Dellenbach, MSOT

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Must be taking: Anti-spasticity

Disqualifiers: Motoneuron injury, Epileptic seizures, others

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

Compensation: Varies

Number of Visits: 30

Duration: 10 weeks

5 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to improve arm movement in individuals with incomplete spinal cord injuries. It focuses on using a device called a transcranial magnetic stimulator (TMS) to strengthen the connection between the brain and muscles, specifically targeting the wrist extensor muscle. This approach, known as MEP Operant Up-conditioning of the Wrist Extensor, aims to enhance the function of this muscle. Individuals with a spinal cord injury at or above the neck level and weak wrist movement may be suitable candidates. The goal is to identify effective therapy strategies to help individuals with spinal cord injuries regain better function. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to innovative therapies for spinal cord injuries.

Will I have to stop taking my current medications?

The trial requires that you keep your current medications the same for at least 3 months. If you are using anti-spasticity medications like baclofen, diazepam, or tizanidine, you can continue taking them as usual.

What prior data suggests that this transcranial magnetic stimulation is safe for spinal cord injury patients?

Research has shown that the treatment under study, called MEP Operant Up-conditioning of the Wrist Extensor, offers potential benefits for individuals with long-term, partial spinal cord injuries. In earlier studies, this method improved muscle activity and movement. Most participants tolerated the treatment well, and no major safety issues arose.

The treatment uses transcranial magnetic stimulation (TMS), which generates a brief magnetic field to stimulate brain cells. This typically causes little to no discomfort, indicating it may be safe for many individuals. However, like any treatment, minor side effects such as mild headaches or scalp discomfort may occur. Discussing any concerns with the study team is important to ensure this treatment is suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Transcranial Magnetic Stimulation (TMS) for spinal cord injury because it offers a non-invasive approach to enhance motor function. Unlike traditional treatments like physical therapy or surgery, which focus on rehabilitation or structural repair, TMS directly stimulates the nervous system using magnetic fields. This method could potentially promote neuroplasticity and improve motor recovery in ways that current therapies cannot. The specific focus on MEP Operant Up-conditioning of the wrist extensor is unique, as it aims to enhance the strength and coordination of specific muscles, offering targeted benefits for individuals with spinal cord injuries.

What evidence suggests that this technique is effective for spinal cord injury?

Research has shown that wrist extensor MEP (motor evoked potential) up-conditioning, which participants in this trial will receive, can improve arm movement in people with spinal cord injuries. This treatment strengthens the connections between the brain and muscles, particularly those used to move the wrist. Studies have found that stronger connections lead to better control over arm muscles. Early findings suggest that this method enhances forearm movement by improving the pathways from the brain to the muscles, potentially leading to better recovery of arm movement in individuals with spinal cord injuries. ^{1 2 6 7 8}

Who Is on the Research Team?

Blair Dellenbach, MSOT

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

This trial is for individuals with incomplete spinal cord injury who are over 6 months post-injury, medically stable, and not expecting medication changes for 3 months. They must have weak wrist extension but can still move their arm voluntarily. People with motoneuron injuries, cognitive impairments, seizures, metal in the skull, pregnancy or certain implants cannot join.

Inclusion Criteria

My weaker arm will be the focus if I have weakness in both wrists.

My current medication will not change for the next 3 months.

I have had a spinal cord injury at or above the C6 level.

Exclusion Criteria

I have metal implants in my head.

I have difficulty with memory or thinking clearly.

I am not pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo training of the brain-spinal cord-muscle response using transcranial magnetic stimulation (TMS) to improve wrist extensor muscle function

10 weeks

30 visits (in-person)

Follow-up

Participants are monitored for changes in spasticity, motor function, and muscle strength after completing the training protocol

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MEP Operant Up-conditioning of the Wrist Extensor

Trial Overview The study tests if training the brain-to-muscle pathway using a magnetic stimulator improves arm movement in those with spinal cord injuries. Participants will train their wrist extensor muscle response to this stimulation over 30 visits lasting about 1.5 hours each.

How Is the Trial Designed?

Group I: MEP Wrist Extensor Up-Conditioning Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Published Research Related to This Trial

In a study involving 26 patients with severe spinal cord injuries and 12 control subjects, transcranial magnetic stimulation revealed low-amplitude motor evoked potentials (MEPs) in 4 patients with clinically complete paralysis, suggesting the presence of spared motor pathways.

Neurological reinforcement techniques, such as muscle contractions and cutaneous stimulation, were crucial for detecting MEPs in patients, highlighting their importance in accurately assessing motor function in spinal cord injury studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reinforcement of motor evoked potentials in patients with spinal cord injury. Hayes, KC., Allatt, RD., Wolfe, DL., et al.[2007]

In a study involving 97 individuals with spinal cord injury and 20 able-bodied subjects, noninvasive transcranial magnetic stimulation (TMS) revealed that those with motor-incomplete injuries to the cervical or thoracic spinal cord were more likely to have muscle responses in their foot and ankle compared to thigh muscles, indicating better preservation of function in distal lower limb muscles.

The study found that response latencies for lower limb muscles were similar between individuals with cervical or thoracic injuries and able-bodied subjects, suggesting normal motor conduction below the injury site, while those with thoracolumbar injuries showed preserved function in proximal muscles but absent responses in distal muscles, indicating a unique pattern of motor function preservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distribution and latency of muscle responses to transcranial magnetic stimulation of motor cortex after spinal cord injury in humans. Calancie, B., Alexeeva, N., Broton, JG., et al.[2007]

In a proof-of-concept study involving three adults with cervical spinal cord injury, repetitive QuadroPulse transcranial magnetic stimulation (rTMS(QP)) showed functional benefits, particularly in improving walking speed and cortical excitability without any adverse effects.

The combination of rTMS(QP) with targeted exercises led to even greater improvements in motor function, suggesting that this approach could be effective and warrants further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of QuadroPulse rTMS for improving motor function after spinal cord injury: Three case studies. Alexeeva, N., Calancie, B.[2018]

In a study involving 11 participants with chronic tetraplegia and 10 neurologically healthy individuals, 10-Hz repetitive transcranial magnetic stimulation (rTMS) combined with repetitive task practice (RTP) significantly improved hand function, particularly in the Jebsen-Taylor Hand Function Test, compared to sham-rTMS.

The results suggest that rTMS may enhance the effectiveness of RTP for improving hand function in individuals with tetraplegia, indicating that higher stimulation doses could lead to even greater improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvements in hand function in adults with chronic tetraplegia following a multiday 10-Hz repetitive transcranial magnetic stimulation intervention combined with repetitive task practice. Gomes-Osman, J., Field-Fote, EC.[2018]

The pilot study found that the paired associative stimulation (PAS) protocol using transcranial magnetic stimulation (TMS) significantly increased corticospinal excitability in both healthy subjects and spinal cord injury (SCI) patients with good motor recovery, suggesting enhanced sensorimotor plasticity.

In contrast, SCI patients with poor functional recovery showed only a non-significant increase in motor-evoked potential (MEP) amplitude, indicating that the ability to induce excitability changes may be linked to the extent of motor recovery after injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abnormal cortical neuroplasticity induced by paired associative stimulation after traumatic spinal cord injury: A preliminary study. Versace, V., Langthaler, PB., Höller, Y., et al.[2019]

Patients with incomplete spinal cord injury showed higher thresholds for motor evoked potentials and longer latencies in EMG responses to transcranial magnetic stimulation compared to healthy controls, indicating altered motor cortex function.

The longer latency difference between compound motor evoked potentials and suppression of voluntary contraction in patients suggests a potential impairment in cortical inhibition, which may play a role in the recovery of motor function after injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responses of thenar muscles to transcranial magnetic stimulation of the motor cortex in patients with incomplete spinal cord injury. Davey, NJ., Smith, HC., Wells, E., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05321017

Wrist Extensor MEP Up-conditioning for Individuals With ... The purpose of this study is to examine the relationship between common clinical assessments and measurements of the function of brain-spinal cord-muscle ...

2. reporter.nih.gov reporter.nih.gov/project-details/11033806

Project Details - NIH RePORTER Building on those studies, this project will examine the effects of wrist extensor MEP operant up-conditioning in people with chronic cervical SCI.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07179822

Motoneuron Recruitment and Motor Evoked Potential Up ... Here, investigators hypothesize that wrist extensor MEP up-conditioning can improve forearm motor functions in people with cervical SCI by ...

4. reporter.nih.gov reporter.nih.gov/project-details/11119385

Can MEP conditioning improve corticospinal ... - NIH RePORTER Here, we hypothesize that wrist extensor MEP up-conditioning can improve forearm motor functions in people with cervical SCI by increasing the corticospinal ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05321017/wrist-extensor-mep-up-conditioning-for-individuals-with-incomplete-spinal-cord-injury

Wrist Extensor MEP Up-conditioning for Individuals With ... The purpose of this study is to examine the relationship between common clinical assessments and measurements of the function of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6442914/

Operant conditioning of the motor-evoked potential and ... In people with chronic incomplete spinal cord injury (SCI), MEP up-conditioning increased TA activity and improved dorsiflexion during locomotion, while in ...

7. withpower.com withpower.com/trial/up-conditioning-for-spinal-cord-injury-b9463

Up-conditioning for Spinal Cord Injury (uMEP2 Trial) This trial is for individuals with chronic cervical spinal cord injury, specifically those who have quadriplegia or tetraplegia. Participants should be able to ...

8. reporter.nih.gov reporter.nih.gov/search/gEb2ZgDZC0C9dn1_WSpJLA/project-details/11033806

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