Spinal Cord Stimulation for Spinal Cord Injury

Overseen By Andrea Willhite, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Louisville

Disqualifiers: Depression, Cardiovascular, Pulmonary, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Respiratory motor control deficit is the leading cause of morbidity and mortality in patients with spinal cord injury. The long-term goal of this NIH-funded study is to develop a rehabilitation strategy for respiration in patients with spinal cord injury as a standard of care. Respiratory function in patients with chronic spinal cord injury can be improved by using inspiratory-expiratory pressure threshold respiratory training protocol. However, the effectiveness of this intervention is limited by the levels of functional capacity preserved below the neurological level of injury. Preliminary data obtained for this study demonstrate that electrical spinal cord stimulation applied epidurally at the lumbar level in combination with respiratory training can activate and re-organize spinal motor networks for respiration. This study is designed to investigate respiratory motor control-related responses to epidural spinal cord stimulation alone and in combination with respiratory training. By characterization of respiratory muscle activation patterns using surface electromyography in association with pulmonary functional and respiration-related cardiovascular measures, the investigators expect to determine the specific stimulation parameters needed to increase spinal excitability below level of injury to enhance responses to the input from supraspinal centers that remain after injury and to promote the neural plasticity driven by the respiratory training. This hypothesis will be tested by pursuing two Specific Aims: 1) Evaluate the acute effects of epidural spinal cord stimulation on respiratory functional and motor control properties; and 2) Evaluate the effectiveness of epidural spinal cord stimulation combined with respiratory training.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that respiratory muscle strength training can improve muscle strength by up to 50% in people with spinal cord injuries. Additionally, combining transcutaneous spinal cord stimulation with inspiratory muscle training significantly improved breathing abilities in individuals with cervical spinal cord injuries. ^{1 2 3 4 5}

Is spinal cord stimulation generally safe for humans?

Research on spinal cord stimulation, including studies on animals and humans, suggests it can be safe and beneficial for improving respiratory function and muscle strength after spinal cord injury. However, more research is needed to confirm long-term safety and effectiveness. ^{2 6 7 8 9}

How does the treatment Spinal Cord Stimulation for Spinal Cord Injury differ from other treatments?

This treatment is unique because it uses electrical stimulation of the spinal cord to improve respiratory function, which is not typically addressed by other treatments for spinal cord injury. It combines respiratory muscle training with spinal cord stimulation to enhance breathing and coughing abilities, offering a novel approach to address respiratory impairments in patients with spinal cord injuries. ^{2 6 7 8 9}

Research Team

Alexander Ovechkin, MD, PhD

Principal Investigator

University of Louisville

Eligibility Criteria

This trial is for adults over 18 with stable, non-progressive spinal cord injuries between C3-T1, who have had the injury for at least two years and have a significant deficit in lung function. It's not suitable for those with severe musculoskeletal pain, unhealed fractures, contractures, active infections or major cardiovascular diseases among other exclusions.

Inclusion Criteria

My spinal cord injury is stable and between the C3 and T1 vertebrae.

My health condition is stable.

I am 18 years old or older.

Exclusion Criteria

I have a significant hormone-related condition.

I have an illness related to HIV/AIDS.

I do not have any major illnesses that would prevent me from doing breathing exercises.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo epidural spinal cord stimulation and respiratory training

12 months

Regular visits for stimulation and training sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Respiratory Training
• Spinal Cord Epidural Stimulation

Trial Overview The study tests how well electrical stimulation of the spine combined with breathing exercises can help control breathing in people with chronic spinal cord injuries. It aims to find specific stimulation settings that improve neural responses and promote recovery of respiratory functions.

Participant Groups

Group I: Spinal Cord Stimulation and Respiratory Training Experimental Treatment 2 Interventions

Research subjects with implanted stimulator undergoing stimulation intervention in combination with respiratory training.

Group II: Spinal Cord Stimulation Active Control 1 Intervention

Research subjects with implanted stimulator undergoing stimulation intervention.

Group III: Respiratory Training Active Control 1 Intervention

Research subjects with no implanted stimulator undergoing RT intervention.

Who Is Running the Clinical Trial?

University of Louisville

Lead Sponsor

Trials

353

Recruited

76,400+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

A 4-week expiratory muscle strength training program, using a pressure threshold device, showed up to a 50% improvement in respiratory muscle strength among healthy individuals and those with conditions like multiple sclerosis and spinal cord injury.

The training protocol, which involves 15-20 minutes of daily exercises five times a week, is designed to enhance expiratory muscle strength and may also positively impact functional outcomes and brain plasticity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory muscle strength training: functional outcomes versus plasticity. Sapienza, CM., Wheeler, K.[2022]

In a randomized controlled trial with 22 cervical spinal cord injury (cSCI) subjects, transcutaneous spinal cord stimulation (tSCS) combined with inspiratory muscle training (IMT) significantly improved respiratory function, including reduced breathlessness and increased thoracic muscle strength.

Subjects receiving tSCS + IMT showed notable enhancements in maximum inspiratory pressure, maximum expiratory pressure, and forced vital capacity, while those who only underwent IMT did not experience significant changes, highlighting the potential of tSCS as an effective adjunct therapy for respiratory rehabilitation in cSCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Spinal Cord Stimulation Improves Respiratory Muscle Strength and Function in Subjects with Cervical Spinal Cord Injury: Original Research. Kumru, H., García-Alén, L., Ros-Alsina, A., et al.[2023]

Inspiratory muscle training (IMT) was found to be feasible and safe for seven adult patients with acute complete cervical or thoracic spinal cord injuries, with all planned sessions successfully delivered without any adverse events.

Some participants showed improvements in lung function, with increases in maximal inspiratory pressure for four individuals and forced vital capacity for three, suggesting potential efficacy of IMT in enhancing respiratory function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inspiratory muscle training is feasible and safe for patients with acute spinal cord injury. McDonald, T., Stiller, K.[2020]

Resistive inspiratory muscle training (RIMT) showed a significant short-term improvement in maximum inspiratory pressure (MIP) in 40 participants with spinal cord injury (SCI) during an 8-week inpatient rehabilitation program.

However, the long-term benefits of RIMT were not sustained after the intervention, and no significant effects were observed on other respiratory or functional outcomes, except for an immediate improvement in mental health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistive inspiratory muscle training in people with spinal cord injury during inpatient rehabilitation: a randomized controlled trial. Postma, K., Haisma, JA., Hopman, MT., et al.[2014]

In a pilot study involving 6 participants with spinal cord injuries, an 8-week community exercise program that included inspiratory muscle training (IMT) led to significant improvements in functional measures such as transfer times and trunk strength.

Participants reported positive impacts from the program, suggesting that combining IMT with community exercise may help reduce respiratory complications and improve overall health outcomes for individuals with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Community exercise for individuals with spinal cord injury with inspiratory muscle training: A pilot study. Leathem, JM., Macht-Sliwinski, M., Boak, S., et al.[2022]

Closed-loop electrical epidural stimulation (CLES) applied after a cervical spinal cord injury in rats showed promising results in enhancing respiratory function by facilitating neuroplasticity in spinal respiratory pathways.

This study is the first to demonstrate that CLES can effectively promote respiratory neuroplasticity following a C2 hemisection injury, suggesting it could be a potential therapy for restoring breathing in patients with cervical spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Closed-Loop, Cervical, Epidural Stimulation Elicits Respiratory Neuroplasticity after Spinal Cord Injury in Freely Behaving Rats. Malone, IG., Kelly, MN., Nosacka, RL., et al.[2023]

Lower thoracic spinal cord stimulation (SCS) effectively activates expiratory muscles in individuals with tetraplegia, achieving high peak airflow rates and airway pressures similar to those seen in healthy individuals during a strong cough.

In a clinical trial involving 9 participants, combined stimulation of two electrode leads produced the highest airflow rates (8.6 L/s) and airway pressures (137 cmH2O), demonstrating the potential of SCS to enhance respiratory function in patients with cervical spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lower thoracic spinal cord stimulation to restore cough in patients with spinal cord injury: results of a National Institutes of Health-sponsored clinical trial. Part I: methodology and effectiveness of expiratory muscle activation. DiMarco, AF., Kowalski, KE., Geertman, RT., et al.[2021]

Closed-loop epidural stimulation (CL-ES) can restore breathing activity in paralyzed hemidiaphragms in a rat model of cervical spinal cord injury, demonstrating its potential as a therapeutic intervention for respiratory deficits.

After a 20-minute session of CL-ES, some rats exhibited spontaneous diaphragm activity even after stimulation ceased, suggesting that this treatment may lead to lasting improvements in respiratory function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Closed-loop cervical epidural stimulation partially restores ipsilesional diaphragm EMG after acute C2 hemisection. Mickle, AR., Peñaloza-Aponte, JD., Coffey, R., et al.[2023]

Lower thoracic spinal cord stimulation (SCS) effectively activates expiratory muscles in dogs, demonstrating significant changes in airway pressure generation, which could help restore effective coughing in patients with spinal cord injuries.

The study showed that SCS can produce substantial positive airway pressures across various lung volumes, indicating its potential as a clinically useful method for improving respiratory function in individuals with paralysis of expiratory muscles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical activation of the expiratory muscles to restore cough. DiMarco, AF., Romaniuk, JR., Supinski, GS.[2007]

References

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

Respiratory muscle strength training: functional outcomes versus plasticity. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous Spinal Cord Stimulation Improves Respiratory Muscle Strength and Function in Subjects with Cervical Spinal Cord Injury: Original Research. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Inspiratory muscle training is feasible and safe for patients with acute spinal cord injury. [2020]

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

Resistive inspiratory muscle training in people with spinal cord injury during inpatient rehabilitation: a randomized controlled trial. [2014]

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

Community exercise for individuals with spinal cord injury with inspiratory muscle training: A pilot study. [2022]

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

Closed-Loop, Cervical, Epidural Stimulation Elicits Respiratory Neuroplasticity after Spinal Cord Injury in Freely Behaving Rats. [2023]

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

Lower thoracic spinal cord stimulation to restore cough in patients with spinal cord injury: results of a National Institutes of Health-sponsored clinical trial. Part I: methodology and effectiveness of expiratory muscle activation. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Closed-loop cervical epidural stimulation partially restores ipsilesional diaphragm EMG after acute C2 hemisection. [2023]

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

Electrical activation of the expiratory muscles to restore cough. [2007]