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

175 Participants Needed

Trial Summary

What is the purpose of this trial?

The overall goals of this proposal are to examine the contribution of physiological pathways to the control of grasping behaviors after cervical SCI, and to maximize the recovery of grasping by using tailored non-invasive brain stimulation and acoustic startle protocols with motor training. The investigators propose to study two basic grasping behaviors, which are largely used in most daily-life activities: a precision grip and a power grip.

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 data supports the effectiveness of the treatment iTMS, Transcranial Magnetic Stimulation, Intermittent Theta-Burst Stimulation, Sham iTMS, Sham Interleaved Transcranial Magnetic Stimulation, Sham iTMS for spinal cord injury?

Research shows that intermittent theta-burst stimulation (iTBS), a type of brain stimulation, can create short-term changes in nerve activity in people with spinal cord injuries, which might help improve movement. In animal studies, repeated iTBS sessions increased nerve growth and motor function, suggesting potential benefits for recovery. ^{1 2 3 4 5}

Is intermittent theta-burst stimulation (iTBS) safe for humans?

Intermittent theta-burst stimulation (iTBS) is generally considered safe, non-invasive, and well-tolerated in humans, as shown in studies involving people with spinal cord injuries. ^{1 2 4 5 6}

How does the treatment of brain stimulation and motor training for spinal cord injury differ from other treatments?

This treatment combines brain stimulation, specifically intermittent theta burst stimulation (iTBS), with motor training to enhance neural plasticity and motor function in spinal cord injury patients. Unlike traditional therapies, iTBS aims to alter corticospinal excitability, potentially leading to improved motor recovery by promoting short-term and possibly long-term changes in neural output. ^{1 2 3 4 5}

Research Team

Monica Perez, PhD

Principal Investigator

Edward Hines Jr. VA Hospital, Hines, IL

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation with Intermittent Theta Burst Stimulation Alters Corticospinal Output in Patients with Chronic Incomplete Spinal Cord Injury. [2020]

2. United States 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. [2021]

3. Sweden pubmed.ncbi.nlm.nih.gov

Cerebral Theta-Burst Stimulation Combined with Physiotherapy in Patients with Incomplete Spinal Cord Injury: A Pilot Randomized Controlled Trial. [2023]

4. England 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. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation modulates biceps brachii corticomotor excitability in individuals with tetraplegia. [2023]

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

Effects of intermittent theta burst stimulation on spasticity after spinal cord injury. [2019]