Neurostimulation for Spinal Cord Injury

Overseen By Sri Ramya Vemulakonda, M.B.B.S

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Shirley Ryan AbilityLab

Must not be taking: CNS drugs, Bupropion

Disqualifiers: Major depression, Seizures, Pregnancy, others

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

Compensation: Varies

Number of Visits: 43

Duration: 14 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to learn more about the connections between the brain, nerves, and diaphragm after experiencing a cervical spinal cord injury (SCI).The main question it aims to answer is: Changes in respiratory function and recovery using stimulation and respiratory exercise training in spinal cord-injured individuals. Participants will complete a maximum of 55 study visits. They will be asked to complete about 40 treatment sessions which include multiple stimulation sessions over the scalp and neck, followed by about 60 minutes of respiratory training. Assessment sessions will be completed prior at baseline, after 20 sessions and after 40 sessions of study treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically Bupropion, Dolutegravir, Lacosamide, Trilaciclib, or drugs that prolong the PR Interval. If you are on any of these, you would need to stop them to participate.

What data supports the effectiveness of the treatment Neurostimulation for Spinal Cord Injury?

Research shows that various forms of electrical stimulation, such as epidural and transcutaneous stimulation, can help improve movement and reduce pain in people with spinal cord injuries. For example, studies have found that these treatments can lead to better walking ability, increased muscle strength, and significant pain relief in many patients. ^{1 2 3 4 5}

Is neurostimulation generally safe for humans?

Neurostimulation, including various forms like electrical stimulation and epidural electrical stimulation, is generally considered safe when proper precautions are taken. However, there are risks such as tissue burns and neurologic injury, which can be minimized by following safety guidelines, ensuring proper electrode placement, and using appropriate equipment. In some cases, like with an infant with spina bifida, electrical stimulation was found to be safe and well tolerated over a 12-month period. ^{6 7 8 9 10}

How does the treatment Neurostimulation for Spinal Cord Injury differ from other treatments for this condition?

Neurostimulation for Spinal Cord Injury is unique because it uses electrical stimulation techniques, such as epidural and transcutaneous spinal cord stimulation, to activate and retrain spinal circuits, which can improve motor functions and respiratory control. Unlike traditional treatments, this approach directly targets the spinal cord to promote regeneration and functional recovery, offering a novel method for rehabilitation in patients with spinal cord injuries. ^{2 3 9 11 12}

Research Team

Monica Perez, PhD

Principal Investigator

Shirley Ryan AbilityLab

Eligibility Criteria

This trial is for adults aged 18-85 with a cervical spinal cord injury at C1-C5 level, at least 6 months post-injury. They must have respiratory deficits and either use mechanical ventilation or have vital capacity less than 80% predicted. A family member or caregiver must be able to operate the ventilator during visits. Exclusions include dependence on diaphragmatic pacer, certain medications, brain injuries, seizures, pregnancy, metal in skull, other major illnesses or conditions.

Inclusion Criteria

I need a ventilator to breathe or my lung capacity is less than 80% due to a spinal injury.

Must have a family member or caregiver who is trained and willing to operate the mechanical ventilator during study visits.

I am between 18 and 85 years old.

Exclusion Criteria

I have a history of seizures or epilepsy.

I have a brain condition not caused by seizures and I'm not on seizure medication.

I am taking medication that could increase my risk of seizures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 40 treatment sessions including multiple stimulation sessions over the scalp and neck, followed by about 60 minutes of respiratory training

14 weeks

40 visits (in-person)

Assessment

Assessment sessions are completed at baseline, after 20 sessions, and after 40 sessions of study treatment

14 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Neurostimulation
• Respiratory training

Trial Overview The study tests how neurostimulation combined with respiratory training affects breathing function after a cervical spinal cord injury. Participants undergo up to 55 visits including about 40 treatment sessions of scalp and neck stimulation followed by an hour of respiratory exercises. Their breathing function is assessed before starting treatments, midway and after completing all sessions.

Participant Groups

Group I: Neurostimulation for respiratory function after spinal cord injury Experimental Treatment 2 Interventions

Efficacy of STDP on respiratory function.

Neurostimulation is already approved in United States, European Union for the following indications:

Approved in United States as Neurostimulation for:

• Respiratory dysfunction in spinal cord injury patients

Approved in European Union as Neurostimulation for:

• Respiratory failure in spinal cord injury patients
• Neuropathic pain relief

Who Is Running the Clinical Trial?

Shirley Ryan AbilityLab

Lead Sponsor

Trials

212

Recruited

17,900+

Findings from Research

Functional electrical therapy (FET) significantly enhances movement recovery in patients with central nervous system lesions by promoting muscle activation and improving coordination, as evidenced by improved scores on the Upper Extremity Function Test and Functional Independence Measure.

FET not only strengthens the directly stimulated muscles but also improves overall functional ability and proprioception, leading to increased range of motion, reduced spasticity, and better performance in daily activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurorehabilitation of upper extremities in humans with sensory-motor impairment. Popovic, DB., Popovic, MB., Sinkjaer, T.[2022]

Epidural electrical stimulation of the lumbosacral spinal cord has been shown to improve locomotion and standing in various preclinical models with severe spinal cord injuries, indicating its potential as a therapeutic intervention.

The review highlights that while the stimulation shows promise, the exact mechanisms by which it enhances sensorimotor functions are still not fully understood, which poses challenges for its clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidural electrical stimulation to facilitate locomotor recovery after spinal cord injury. Audet, J., Lecomte, CG.[2022]

Transtraumatic epidural electrostimulation (TEES) combined with treadmill exercise in pigs after spinal cord injury showed significant restoration of motor function, including voluntary movement in hindlimbs, after 6 weeks of treatment.

TEES effectively activated spinal cord structures above and below the injury site, indicating its potential as a neuromodulation technique for enhancing spinal cord regeneration and aiding in neurorehabilitation protocols for spinal cord injury patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transtraumatic Epidural Electrostimulation of the Spinal Cord in a Pig Model. Shevchenko, RV., Fadeev, FO., Izmailov, AA., et al.[2023]

Transcutaneous electrical neurostimulation (TENS) was applied to 20 patients with acute spinal cord injuries and associated severe pain, resulting in over 50% pain relief for 75% of the patients.

TENS is advantageous due to its ease of application, minimal complications, promotion of intestinal peristalsis, and the ability to reduce reliance on narcotic pain medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous electrical neurostimulation in musculoskeletal pain of acute spinal cord injuries. Richardson, RR., Meyer, PR., Cerullo, LJ.[2019]

In a study involving four patients with motor complete spinal cord injuries, two individuals achieved over-ground walking after intensive locomotor treadmill training combined with spinal cord epidural stimulation, demonstrating potential for recovery even years post-injury.

All four patients were able to achieve independent standing and trunk stability after the training, although one patient experienced a hip fracture during the process, highlighting the need for careful monitoring during rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Cord Injury. Angeli, CA., Boakye, M., Morton, RA., et al.[2018]

Electric stimulation is commonly used for diagnosis and therapy in spinal cord injury patients, but it can lead to tissue burns, as demonstrated in two reported cases.

To prevent burns during electric stimulation, it is crucial to use electrodes with a large surface area, ensure uniform contact with the skin, maintain a good conducting interface, provide adequate ventilation for heat dissipation, and avoid sharp electrode corners or damaged wires.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Burns in functional electric stimulation: two case reports. Balmaseda, MT., Fatehi, MT., Koozekanani, SH., et al.[2004]

The Neurostimulation Appropriateness Consensus Committee (NACC) aims to enhance the safety of neurostimulation procedures by providing updated recommendations based on expert consensus and best evidence.

The International Neuromodulation Society (INS) has established guidelines that, when followed, are expected to minimize the risk of neurological injuries and complications associated with the surgical implantation of neurostimulation devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Neurostimulation Appropriateness Consensus Committee (NACC) Safety Guidelines for the Reduction of Severe Neurological Injury. Deer, TR., Lamer, TJ., Pope, JE., et al.[2022]

An infant with myelomeningocele showed unexpected improvements, including somatosensory responses and spontaneous movements in the trunk and lower extremities after 12 months of electrical stimulation treatment, which included functional and transcutaneous spinal cord stimulation.

Both electrical stimulation protocols were found to be safe and well tolerated, marking a novel approach in the management of children with spina bifida, as such treatments had not been previously documented in medical literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Exploratory Electrical Stimulation Protocol in the Management of an Infant With Spina Bifida: A Case Report. Motavalli, G., McElroy, JJ., Alon, G.[2020]

Epidural spinal electrostimulation (ESES) has shown promising results in improving spinal spasticity and mobility by 20 to 30% in patients with multiple sclerosis and myelopathy, indicating its efficacy in treating severe central motor disturbances.

In addition to mobility improvements, ESES led to a complete disappearance of spastic cramps in all treated cases and significant pain relief in three patients with chronic pain, suggesting its potential as a non-surgical intervention for chronic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Epidural spinal electrostimulation (ESES) in patients with chronic pain and central motor disturbances (author's transl)]. Klingler, D., Kepplinger, B., Gerstenbrand, F., et al.[2006]

Electrical stimulation has shown promising results in pain control, achieving up to 80% success for acute pain and 50% for chronic pain, using various methods like transcutaneous and spinal cord stimulation.

This therapy also has potential for restoring lost functions, such as improving respiration and bladder control, and is safe as its effects are reversible and non-destructive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical stimulation: new methods for therapy and rehabilitation. Ray, CD.[2004]

Transcutaneous electrical spinal cord neuromodulation (TESCoN) significantly improves breathing and coughing abilities in a patient with chronic tetraplegia, demonstrating its potential as a noninvasive treatment for respiratory dysfunction following spinal cord injury.

The benefits of TESCoN therapy were observed not only during treatment but also persisted for several days after the therapy was stopped, indicating a lasting positive effect on respiratory function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enabling respiratory control after severe chronic tetraplegia: an exploratory case study. Gad, P., Kreydin, E., Zhong, H., et al.[2021]

Epidural neurostimulation is a promising treatment for refractory chronic musculoskeletal pain, particularly effective for conditions like radicular pain and postoperative lumbar pain, as indicated by a rigorous selection process that requires at least a 50% pain reduction from preliminary neurostimulation.

In a study of 20 patients with postoperative lumbar arachnoepiduritis, the results of epidural stimulation were encouraging, suggesting that this two-stage surgical procedure can provide significant pain relief for eligible patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of chronic pain of the musculoskeletal system by epidural stimulation]. Husson, JL., Meadeb, J., Eudier, F., et al.[2011]

References

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

Neurorehabilitation of upper extremities in humans with sensory-motor impairment. [2022]

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

Epidural electrical stimulation to facilitate locomotor recovery after spinal cord injury. [2022]

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

Transtraumatic Epidural Electrostimulation of the Spinal Cord in a Pig Model. [2023]

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

Transcutaneous electrical neurostimulation in musculoskeletal pain of acute spinal cord injuries. [2019]

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

Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Cord Injury. [2018]

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

Burns in functional electric stimulation: two case reports. [2004]

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

The Neurostimulation Appropriateness Consensus Committee (NACC) Safety Guidelines for the Reduction of Severe Neurological Injury. [2022]

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

An Exploratory Electrical Stimulation Protocol in the Management of an Infant With Spina Bifida: A Case Report. [2020]

9. Austria pubmed.ncbi.nlm.nih.gov

[Epidural spinal electrostimulation (ESES) in patients with chronic pain and central motor disturbances (author's transl)]. [2006]

10. Sweden pubmed.ncbi.nlm.nih.gov

Electrical stimulation: new methods for therapy and rehabilitation. [2004]

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

Enabling respiratory control after severe chronic tetraplegia: an exploratory case study. [2021]

12. France pubmed.ncbi.nlm.nih.gov

[Treatment of chronic pain of the musculoskeletal system by epidural stimulation]. [2011]