Brain Stimulation + Motor Training for Spinal Cord Injury

Overseen By Monica A Perez, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must not be taking: CNS drugs

Disqualifiers: Pulmonary, Cardiovascular, Orthopedic, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores ways to improve hand function in individuals with spinal cord injuries (SCI) using non-invasive brain stimulation techniques and motor training. The goal is to enhance two key hand grips: the precision grip for small objects and the power grip for larger ones. Participants will receive various treatments, including real or sham (fake) brain stimulation, such as Intermittent Theta-Burst Stimulation (iTMS), to determine the most effective combination. Ideal candidates have had an SCI for over a year, with the injury located at the neck level (C8 or above), and retain some hand function. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could improve hand function for many.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking drugs that affect the central nervous system and lower the seizure threshold.

What prior data suggests that these brain stimulation and motor training protocols are safe for spinal cord injury patients?

Research has shown that intermittent theta burst stimulation (iTMS) is generally safe for people with spinal cord injuries. One study found that applying iTMS to the brain area controlling movement did not cause major side effects and improved arm and hand function.

Other studies suggest that iTMS can reduce pain and support recovery in people with spinal cord injuries without significant side effects. The research indicates that iTMS is a safe option for enhancing movement recovery.

These findings provide strong evidence of iTMS's safety, particularly for those with spinal cord injuries. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the brain stimulation and motor training protocol for spinal cord injury (SCI) because it uses innovative techniques like intermittent transcranial magnetic stimulation (iTMS) and acoustic startle stimuli to potentially enhance muscle function and grip strength. Unlike current treatments that primarily focus on physical rehabilitation, this approach aims to stimulate brain pathways directly, which could lead to improved hand control by tapping into distinct brainstem and corticospinal pathways. This could offer a new avenue for recovery by not only promoting muscle strength but also enhancing the control over muscle movements, potentially leading to better functional outcomes in SCI patients.

What evidence suggests that this trial's treatments could be effective for spinal cord injury?

Research has shown that intermittent theta burst stimulation (iTMS) holds promise for individuals with spinal cord injuries. Studies have found that iTMS can reduce nerve pain and muscle stiffness or spasms in these patients. This treatment is convenient and comfortable, as sessions are shorter than those of similar therapies. Although results have varied, this trial explores iTMS for its potential to improve movement after spinal cord injuries. Participants will receive either iTMS or sham iTMS to assess its effectiveness in stimulating the brain to aid muscle control and recovery. ^{2 6 7 8 9}

Who Is on the Research Team?

Monica Perez, PhD

Principal Investigator

Edward Hines Jr. VA Hospital, Hines, IL

Are You a Good Fit for This Trial?

This trial is for right-handed adults aged 18-85, both healthy and those with chronic spinal cord injury (SCI) at C8 or above. Healthy participants must be able to grip and move their wrists. SCI participants need some wrist movement and the ability to grip, but can't join if they have uncontrolled medical issues, a history of severe mental health problems, head injury or stroke, pacemakers, metal in the skull, seizure history, certain medications lowering seizure threshold or are pregnant.

Inclusion Criteria

I am a healthy right-handed person aged 18-85, able to grip and move my wrists fully.

I am between 18-85 years old with a spinal cord injury above C8, can grip with one hand, and have some wrist movement.

Exclusion Criteria

I do not have uncontrolled health issues or a history of major mental health, head injury, stroke, seizures, or specific spinal cord diseases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Experiment 1a

Examine physiological mechanisms contributing to the control of precision and power grip behaviors using TMS and acoustic startle stimuli.

4 weeks

Multiple sessions (in-person)

Experiment 1b

Test the hypothesis that induced-plasticity protocols will enhance EMG and force output in hand muscles during grasping.

4 weeks

Multiple sessions (in-person)

Experiment 2

Combine iTMS and/or acoustic startle with precision and power grip training to enhance training outcomes.

4 weeks

Multiple sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• iTMS
• Sham iTMS

Trial Overview

The study tests how brain stimulation (iTMS) combined with motor tasks affects grasping function after cervical SCI. Participants will practice precision and power grips while receiving either real iTMS or a sham treatment without actual stimulation. The goal is to see if this combination improves hand function.

How Is the Trial Designed?

Group I: Experiment 1b Active Control 2 Interventions

To accomplish this aim the investigators propose to complete one main experiment. The investigators will use iTMS and/or an acoustic startle stimuli to test the hypothesis that induced-plasticity protocols (iTMS and startle stimuli) will enhance EMG and force output in hand muscles during grasping. In a randomized sham crossover design, SCI and controls will be assigned to two groups: (1) iTMS applied during precision and power grip (two randomized sessions), and (2) startle applied during precision and power grip (two randomized sessions).

Group II: Experiment 2 Active Control 4 Interventions

To accomplish this aim the investigators propose to complete one main experiment. The investigators will combine iTMS and/or acoustic startle with precision and power grip training to test the hypothesis that 'precision and power grip training outcomes will be enhanced by iTMS and startle induced plasticity'. In a randomized sham controlled design, SCI and control subjects will be assigned to: training+iTMS and training+sham iTMS and training+startle and training+sham startle.

Group III: Experiment 1a Active Control 2 Interventions

Examine physiological mechanisms contributing to the control of precision and power grip behaviors. To accomplish this aim the investigators propose to complete one main experiment. The investigators will test the hypotheses that there are two fundamentally distinct modes of hand operation after SCI. One involves brainstem pathways, and permits whole-hand 'power grip', while the other involves corticospinal and motor cortical connections, and allows a wide range of fractionated finger movements (precision grip) after SCI. Measurements of corticospinal, reticulospinal, and motoneuron excitability will be tested during index finger abduction, precision and power grip.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

This study is the first to evaluate intermittent theta burst stimulation (iTBS) in individuals with chronic incomplete spinal cord injury (SCI), showing that a single session can lead to short-term changes in corticospinal excitability, which is crucial for potential functional improvements.

Among the eight participants, iTBS produced varied effects on motor-evoked potentials (MEPs), with some showing increased and others decreased MEPs, highlighting the need for further research to understand the implications of these changes on motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation with Intermittent Theta Burst Stimulation Alters Corticospinal Output in Patients with Chronic Incomplete Spinal Cord Injury. Fassett, HJ., Turco, CV., El-Sayes, J., et al.[2020]

Intermittent theta burst stimulation (iTBS) significantly reduced spasticity in patients with spinal cord injury (SCI), as evidenced by improved motor evoked potentials and lower scores on the Modified Ashworth Scale and Spinal Cord Injury Assessment Tool for Spasticity after treatment.

The effects of iTBS were sustained for up to one week after treatment, indicating its potential as a long-lasting therapeutic option for managing spasticity in SCI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of intermittent theta burst stimulation on spasticity after spinal cord injury. Nardone, R., Langthaler, PB., Orioli, A., et al.[2019]

Intermittent theta burst stimulation (iTBS) significantly increased corticomotor excitability of the biceps brachii in individuals with tetraplegia, as measured by motor evoked potentials (MEPs), compared to a sham treatment.

The increase in MEPs was correlated with the corticomotor conductance potential, suggesting that iTBS may enhance motor function in individuals with spinal cord injury by improving the excitability of motor pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation modulates biceps brachii corticomotor excitability in individuals with tetraplegia. Mittal, N., Majdic, BC., Peterson, CL.[2023]

The study demonstrated that intermittent theta-burst stimulation (iTBS) is safe and tolerable for individuals with upper-limb dysfunction following spinal cord injury, with no serious adverse events reported during the 10-session intervention.

The feasibility of conducting a larger trial was supported by the recruitment of 12 participants, with 10 completing the protocol, indicating that iTBS could potentially improve upper-limb function, although further optimization of the intervention is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta-burst stimulation for upper-limb dysfunction and spasticity in spinal cord injury: a single-blind randomized feasibility study. Gharooni, AA., Nair, KPS., Hawkins, D., et al.[2018]

Cerebral intermittent theta-burst stimulation combined with physiotherapy significantly improved lower extremity motor recovery in 38 adults with incomplete spinal cord injury over 9 weeks, showing better results compared to a sham treatment group.

The study demonstrated significant enhancements in various motor recovery metrics, including lower extremity motor score and walking speed, indicating that this stimulation technique may be an effective adjunct to traditional physiotherapy for improving mobility in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral Theta-Burst Stimulation Combined with Physiotherapy in Patients with Incomplete Spinal Cord Injury: A Pilot Randomized Controlled Trial. Feng, X., Wang, T., Jiang, Y., et al.[2023]

Intermittent theta-burst stimulation (iTBS) significantly increased the expression of growth-associated protein (GAP)-43 in spinal cord tissues, suggesting enhanced axonal regeneration following treatment in an animal model of incomplete spinal cord injury (SCI).

While iTBS improved motor plasticity in all SCI rats, it did not lead to significant changes in locomotor function, indicating that while the treatment may promote neural repair mechanisms, further research is needed to translate these findings into functional improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulatory effects of repetitive transcranial magnetic stimulation on neural plasticity and motor functions in rats with an incomplete spinal cord injury: A preliminary study. Marufa, SA., Hsieh, TH., Liou, JC., et al.[2021]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37982995/

Comparison of intermittent theta burst stimulation and high- ...

Both iTBS and rTMS were effective in reducing spinal cord injury-related neuropathic pain. When safety, convenience, and compliance are considered, iTBS would ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S2772529425000530

nTMS in spinal cord injury: Current evidence, challenges ...

nTMS has shown encouraging preliminary results in both clinical assessment and rehabilitation (motor and pain) of patients with SCI.

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/28598858/

Effects of intermittent theta burst stimulation on spasticity ...

These findings suggest that iTBS may be a promising therapeutic tool for the spasticity in SCI patients.

4.

frontiersin.org

frontiersin.org/journals/neurology/articles/10.3389/fneur.2017.00380/full

Transcranial Magnetic Stimulation with Intermittent Theta ...

To date, repetitive TMS protocols have shown mixed results when assessing recovery of function following SCI (1, 2) with only one report showing ...

5.

centerwatch.com

centerwatch.com/clinical-trials/listings/NCT06248476/intermittent-theta-burst-stimulation-and-repetitive-transcranial-magnetic-stimulation-combined-with-robotic-rehabilitation-on-ambulation-in-spinal-cord-injury-patients

Intermittent Theta Burst Stimulation and Repetitive ...

iTBS lasts shorter than rTMS so that this technique comfortable than rTMS for both patients and also physicians.

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/29895874/

Intermittent Theta-Burst Stimulation for Upper-Limb ...

(2) Determine the safety and tolerability of iTBS over primary motor cortex on upper-limb function in people with spinal cord injury (SCI).

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10374342/

Effects of different transcranial magnetic stimulations on ...

As a new rTMS technique, intermittent theta burst stimulation (iTBS) is also effective at relieving pain. We aimed to establish the pain- ...

8.

frontiersin.org

frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1587060/full

Repetitive transcranial magnetic stimulation for enhancing ...

This narrative review examines the current state of evidence regarding the therapeutic use of rTMS for motor function recovery after SCI.

9.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04727866

Brain Plus Spinal Stimulation for Cervical SCI

Outcomes focus on safety and neurophysiological transmission. The first session is used to determine the target muscle, optimal scalp site for TMS stimulation, ...