Spinal Cord Stimulation + Respiratory Training for Spinal Cord Injury

Overseen By Andrea Willhite, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Louisville

Disqualifiers: Pulmonary, Cardiovascular, Endocrine, Obesity, others

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

Compensation: Varies

Number of Visits: 80

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Respiratory complications are among the leading causes of death in patients with chronic spinal cord injury (SCI). Our previous work showed that pulmonary function can be improved by using our original respiratory training method. However, the effectiveness of this intervention is limited due to the disruption of brain-spinal connections and consequently lowered spinal cord activity below the injury level. Our recent studies showed that electrical stimulation of the spinal cord below the level of injury leads to increased ventilation which indicates activation of the spinal cord structures related to respiration. These findings indicate that spinal cord stimulation can be a promising therapeutic additive to the treatment. The goal of this study is to justify the establishment of a new direction in rehabilitation for patients with SCI by using a non-invasive spinal cord stimulation in combination with respiratory training. Our aims are: 1) to evaluate the effects of such stimulation applied to the injured spinal cord on pulmonary function and respiratory muscle activity, and 2) to evaluate the effectiveness and therapeutic mechanisms of the spinal cord stimulation combined with respiratory training. Thirty-six individuals with chronic SCI will be recruited and assigned to three groups to receive respiratory training or spinal cord stimulation alone or a combination of them. All participants will be tested before and after cycles of experimental procedures with/or without stimulation. Our hypotheses will be confirmed if the respiratory training combined with spinal cord stimulation results in the most enhanced positive effects.

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.

Is spinal cord stimulation combined with respiratory training safe for humans?

Research indicates that inspiratory muscle training and spinal cord stimulation are generally safe for individuals with spinal cord injuries, as studies have shown improvements in respiratory function without significant adverse effects. ^{1 2 3 4 5}

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

This treatment is unique because it combines respiratory training with transcutaneous spinal cord stimulation (tSCS), which is a non-invasive method that uses electrical stimulation to improve respiratory muscle strength and function. Unlike other treatments that may focus solely on respiratory exercises, this approach aims to enhance recovery by stimulating the spinal cord to improve breathing and coughing abilities in patients with spinal cord injuries. ^{1 2 4 6 7}

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

Research shows that combining transcutaneous spinal cord stimulation (tSCS) with inspiratory muscle training (IMT) significantly improves breathing and coughing abilities in people with cervical spinal cord injury, compared to IMT alone. Additionally, respiratory muscle strength training has been shown to improve muscle strength by up to 50% in various populations, including those with spinal cord injury. ^{1 2 3 8 9}

Who Is on the Research Team?

Alexander Ovechkin, MD, PhD

Principal Investigator

University of Louisville

Are You a Good Fit for This Trial?

This trial is for adults over 18 with chronic spinal cord injury (SCI) who have been stable for at least a year and show significant breathing function deficits. It's not suitable for those dependent on ventilators, with major illnesses like heart disease or cancer, obesity, pregnancy, or conditions that could interfere with the training.

Inclusion Criteria

I don't have any major muscle or bone issues, open wounds, or UTIs that could affect my breathing exercises.

Your lung function test shows at least a 15% decrease compared to what is typical for a healthy person.

My spinal cord injury hasn't worsened and I don't need a ventilator. My injury level is above T5 and classified as 'A' or 'B'.

Exclusion Criteria

I have an illness related to HIV/AIDS.

I do not have major esophageal or gastrointestinal issues that would prevent me from undergoing respiratory training or testing.

I have low blood pressure due to another health condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Baseline Assessment

Participants undergo baseline assessments before the intervention

2 weeks

Intervention

Participants receive 80 sessions of Respiratory Training, Spinal Cord Transcutaneous Stimulation, or a combination of both

16 weeks

80 sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Respiratory Training
• Transcutaneous spinal cord stimulator

Trial Overview The study tests if non-invasive spinal cord stimulation combined with respiratory training can improve lung function in SCI patients. Participants are divided into three groups to receive either just the training, just the stimulation, or both together.

How Is the Trial Designed?

Group I: Spinal Cord Transcutaneous Stimulation and Respiratory Training (scTS+RT) group Experimental Treatment 2 Interventions

Participants will undergo 80 scTS combined with the RT while seated in their own wheelchairs with an approximately 45° head-up tilt. The scTS will be administered using the Neostim/Biostim (Cosyma Inc., Denver CO) and Standard threshold Positive Expiratory Pressure Device (PEP, Respironics Inc., Cedar Grove, NJ) and standard threshold Inspiratory Muscle Trainer (IMT, Respironics Inc., Cedar Grove, NJ) assembled together using a T-shaped connector with a flanged mouthpiece (Airlife 001504) will be used for the RT as described for the Arms 1 and 2.

Group II: Training (RT) group Active Control 1 Intervention

80 scTS sessions will be administered using the Neostim/Biostim (Cosyma Inc., Denver CO) device applying up to five conductive electrodes placed on the skin at the midline over the thoracic levels as cathodes between T1 to T8, and up to four self-adhesive electrodes located symmetrically on the skin over the iliac crests and shoulders as anodes. During the intervention, optimally configured scTS will be delivered based on the measures assessed during mapping sessions. The scTS with 5 mA-sub-motor threshold intensity with optimal frequency and pulse width will be delivered using 5 min on and 5 min off stimulation periods during interventional bouts. Every research participant will be slowly acclimated to stimulation. Blood pressure, heart rate, and respiratory rate will be closely monitored throughout stimulation sessions in the Lab by using beat-to-beat blood pressure, and respiratory kinematics monitoring.

Group III: Spinal Cord Transcutaneous Stimulation (scTS) group Active Control 1 Intervention

Participants will undergo 80 RT sessions using standard threshold Positive Expiratory Pressure Device (PEP, Respironics Inc., Cedar Grove, NJ) and standard threshold Inspiratory Muscle Trainer (IMT, Respironics Inc., Cedar Grove, NJ) assembled together using a T-shaped connector with a flanged mouthpiece (Airlife 001504). Participants will be trained at the Frazier Rehab Institute and remotely to complete eighty 45-minute sessions during 16 weeks. The participants will be instructed to perform inspiratory and expiratory efforts against a pressure threshold load. The training will be initiated with a load equal to 20% of their individual Maximum Inspiratory Pressure (PImax) and Maximum Expiratory Pressure (PEmax) values with progressive increases as tolerated up to 60% of their baseline PImax and PEmax measures. The goal will be to reach the 60% load of PImax and PEmax during the last week of each month of the training.

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+

Published Research Related to This Trial

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]

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]

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]

A systematic review of 11 studies involving 212 participants with cervical spinal cord injury (SCI) found that respiratory muscle training (RMT) significantly improved vital capacity and respiratory muscle strength without any reported adverse effects.

RMT showed a statistically significant increase in maximal inspiratory and expiratory pressures, indicating its efficacy in enhancing respiratory function for individuals with cervical SCI, although it did not affect forced expiratory volume or dyspnoea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory muscle training for cervical spinal cord injury. Berlowitz, DJ., Tamplin, J.[2022]

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]

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]

Cervical transcutaneous spinal cord stimulation (tSCS) can effectively activate sensory fibers at lower stimulation intensities when the cathode electrode is positioned at the C7 or T1 vertebra, compared to C6, which may enhance rehabilitation outcomes for upper-limb motor recovery after spinal cord injury.

Using smaller electrode sizes not only lowers the activation threshold for sensory fibers but also optimizes the recruitment of these fibers before α-motor fibers, suggesting a strategic approach to improve hand muscle activation during tSCS therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing sensory fiber activation during cervical transcutaneous spinal stimulation using different electrode configurations: A computational analysis. de Freitas, RM., Capogrosso, M., Nomura, T., et al.[2022]

Spinal cord injuries often leave some neural pathways intact, which can be targeted for recovery through various non-invasive respiratory treatments, enhancing neuroplasticity and long-term recovery.

The review discusses current and emerging respiratory training strategies, such as strength training and chemical stimulation, that may not only improve respiratory function but also positively impact other networks, like locomotion, after cervical level spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory Training and Plasticity After Cervical Spinal Cord Injury. Randelman, M., Zholudeva, LV., Vinit, S., et al.[2022]

Citations

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

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

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

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

4. 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]

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

Respiratory muscle training for cervical spinal cord injury. [2022]

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

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

7. England pubmed.ncbi.nlm.nih.gov

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

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

Optimizing sensory fiber activation during cervical transcutaneous spinal stimulation using different electrode configurations: A computational analysis. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Respiratory Training and Plasticity After Cervical Spinal Cord Injury. [2022]