Air Mixture + Electrical Stimulation for Spinal Cord Injury

(AIHH+tSCS Trial)

Overseen By Dana R Johnson, PT, DPT

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Thomas Jefferson University

Disqualifiers: Cardiopulmonary disease, Ventilator support, Pregnancy, others

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

Compensation: Varies

Number of Visits: 8

Duration: 5 weeks

29 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to determine whether people with paralysis due to a spinal cord injury can benefit from breathing short intermittent bouts of air with low oxygen (O2) combined with slightly higher levels of carbon dioxide (CO2), interspaced by breathing room air. The technical name for this therapeutic air mixture is 'acute intermittent hypercapnic-hypoxia,' abbreviated as AIHH. Following exposure to the gas mixture, participants will receive non-invasive electrical stimulation to the spinal cord paired with specific and targeted exercise training. The main question this trial aims to answer is: Can the therapeutic application of AIHH, combined with non-invasive electrical stimulation to the spinal cord plus exercise training, increase the strength of muscles involved in breathing and hand function in people with paralysis due to a spinal cord injury? Participants will be asked to attend a minimum of five study visits, each separated by at least a week. During these visits, participants will be required to: * Answer basic questions about their health * Receive exposure to the therapeutic air mixture (AIHH) * Undergo non-invasive spinal electrical stimulation * Complete functional breathing and arm strength testing * Undergo a single blood draw * Provide a saliva sample Researchers will compare the results of individuals without a spinal cord injury to those of individuals with a spinal cord injury to determine if the effects are similar.

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 this treatment for spinal cord injury?

Research shows that transcutaneous spinal cord stimulation (tSCS) can enhance voluntary movement, muscle strength, and function in people with chronic spinal cord injury. Additionally, high-frequency spinal cord stimulation (HF-SCS) has been shown to activate inspiratory muscles, which may help with breathing in patients with spinal cord injuries. ^{1 2 3 4 5}

Is transcutaneous spinal cord stimulation (tSCS) safe for humans?

Transcutaneous spinal cord stimulation (tSCS) is considered a safe, non-invasive technique for modulating spinal cord activity, as indicated by studies evaluating its effects on spinal cord excitability and motor responses in individuals with spinal cord injury. ^{1 6 7 8 9}

How does the Air Mixture + Electrical Stimulation treatment for spinal cord injury differ from other treatments?

This treatment is unique because it combines Acute Intermittent Hypercapnic Hypoxia (AIHH), which involves controlled exposure to low oxygen levels, with Transcutaneous Spinal Cord Stimulation (tSCS), a non-invasive method that uses electrical currents to stimulate the spinal cord. This combination aims to enhance recovery by promoting neural activity and improving motor function, which is different from traditional treatments that may not use both hypoxia and electrical stimulation together. ^{1 2 4 6 10}

Research Team

Justine Dee, PT

Principal Investigator

Thomas Jefferson University

Eligibility Criteria

Adults aged 18-65 with non-progressive spinal cord injuries from C2-T1, classified as AIS B, C, or D. They should have impaired breathing strength and be able to engage in therapy programs. Must be at least a year post-injury, capable of consent, have caregiver support, and willing to be recorded.

Inclusion Criteria

Has adequate caregiver support to facilitate participation in study

Willingness to undergo non-deidentifiable audio and/or visual recording

You have more than 20% difficulty in breathing compared to normal values.

Exclusion Criteria

I have heart or lung conditions that are not well-managed.

Most of my muscles do not respond due to nerve damage.

I do not have any major health issues that could affect the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Clinical Assessment

Comprehensive clinical assessments to characterize each individual's clinical presentation and SCI, and to determine initial status to monitor safety and responses to study procedures.

1 visit

1 visit (in-person)

Treatment

Participants receive AIHH or Sham exposure followed by tSCS paired with respiratory and upper extremity strength training.

5 weeks

5 visits (in-person), each separated by at least a week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including post-testing of neurophysiology and functional assessments.

1 week

1 visit (in-person)

Treatment Details

Interventions

• Acute Intermittent Hypercapnic Hypoxia
• SHAM Acute Intermittent Hypercapnic Hypoxia
• SHAM Transcutaneous spinal cord stimulation
• Transcutaneous spinal cord stimulation

Trial Overview The trial tests if a mix of low oxygen and high carbon dioxide air (AIHH), along with electrical stimulation and exercise training can improve breathing and hand function in those paralyzed due to spinal injury. It involves health questions, AIHH exposure, stimulation sessions, strength testing, blood draw and saliva sample.

Participant Groups

Group I: SHAM AIHH + tSCS-paired Strength Training Experimental Treatment 2 Interventions

Participants will receive exposure to SHAM AIHH followed by transcutaneous spinal cord stimulation-paired respiratory and upper extremity strength training.

Group II: AIHH + SHAM tSCS-paired Strength Training Experimental Treatment 2 Interventions

Participants will receive exposure to AIHH followed by SHAM transcutaneous spinal cord stimulation-paired respiratory and upper extremity strength training.

Group III: AIHH + tSCS-paired Strength Training Active Control 2 Interventions

Participants will receive exposure to AIHH followed by transcutaneous spinal cord stimulation-paired respiratory and upper extremity strength training.

Group IV: SHAM AIHH + SHAM tSCS-paired Strength Training Placebo Group 2 Interventions

Participants will receive exposure to SHAM AIHH followed by SHAM transcutaneous spinal cord stimulation-paired respiratory and upper extremity strength training.

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

Findings from Research

High-frequency spinal cord stimulation (HF-SCS) can effectively activate the diaphragm and inspiratory intercostal muscles, which is crucial for patients with spinal cord injuries who rely on ventilators.

A computational model identified optimal electrode designs that enhance muscle activation, and these predictions were validated through in vivo canine experiments, suggesting that longer contacts and wider spacing between electrode edges improve the efficacy of HF-SCS for muscle pacing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Model-Based Optimization of Spinal Cord Stimulation for Inspiratory Muscle Activation. Zander, HJ., Kowalski, KE., DiMarco, AF., et al.[2022]

In a pilot study involving 7 individuals with chronic spinal cord injury, the use of transcutaneous electrical spinal cord stimulation (TSCS) combined with functional training led to improvements in upper and lower extremity function, with all participants showing progress on the Capabilities of Upper Extremity Test (CUE-T).

Notably, two participants improved their ASIA impairment scale classification, and five individuals experienced enhanced sensation, demonstrating that TSCS can facilitate recovery even after a plateau in rehabilitation progress, without any serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Electrical Spinal Cord Stimulation to Promote Recovery in Chronic Spinal Cord Injury. Tefertiller, C., Rozwod, M., VandeGriend, E., et al.[2022]

Noninvasive transcutaneous spinal cord stimulation (tSCS) has been shown to effectively induce muscle activation in individuals with spinal cord injury, based on a systematic review of 13 studies involving 55 participants.

While tSCS appears to enhance voluntary movement, muscle strength, and function, further research is needed to determine the optimal electrode placement and current intensity for maximum efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Spinal Cord Stimulation and Motor Rehabilitation in Spinal Cord Injury: A Systematic Review. Megía García, A., Serrano-Muñoz, D., Taylor, J., et al.[2021]

High frequency spinal cord stimulation (HF-SCS) effectively activated the inspiratory intercostal muscles in anesthetized dogs, maintaining artificial ventilation for over 5 hours after spinal cord injury and phrenic nerve damage.

The technique demonstrated the ability to induce hyperventilation, lowering carbon dioxide levels in the blood, suggesting it could be a promising method for restoring ventilation in patients with tetraplegia who lack diaphragm function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intercostal muscle pacing with high frequency spinal cord stimulation in dogs. DiMarco, AF., Kowalski, KE.[2021]

In a study of 18 patients with chronic pain who did not respond to conventional spinal cord stimulation (SCS), 61% were successfully treated with 10-kHz high-frequency (HF10) stimulation, showing significant pain relief in both low-back and limb pain after 12 months.

The study suggests that HF10-SCS can effectively rescue patients from conventional SCS failure without needing additional surgery, although factors like obesity and gender may influence treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-frequency spinal cord stimulation as rescue therapy for chronic pain patients with failure of conventional spinal cord stimulation. Cordero Tous, N., Sánchez Corral, C., Ortiz García, IM., et al.[2021]

Transcutaneous spinal cord stimulation (tSCS) shows potential for generating motor activity in individuals with spinal cord injury, but the overall quality of the studies reviewed was poor-to-fair, indicating a need for more rigorous research.

The review identified significant variability in stimulation parameters and outcome measurements across the 25 studies analyzed, highlighting the necessity for standardized methods to improve the reliability and comparability of tSCS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous spinal cord stimulation and motor responses in individuals with spinal cord injury: A methodological review. Taylor, C., McHugh, C., Mockler, D., et al.[2022]

In a double-blinded study involving 2 male patients with incomplete spinal cord injury, anodal transcutaneous spinal direct current stimulation (tsDCS) improved all measured outcomes, including gait and balance, while cathodal tsDCS showed mixed results.

Both types of tsDCS were able to modulate corticospinal excitability, indicating that this non-invasive method could be a promising approach for enhancing rehabilitation in patients with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal direct current stimulation with locomotor training in chronic spinal cord injury. Abualait, TS., Ibrahim, AI.[2021]

Transcutaneous spinal direct current stimulation (tsDCS) is a safe technique that can effectively modulate spinal cord excitability, as shown by changes in motor-evoked potentials (MEPs) in healthy subjects after stimulation.

The study found that cathodal tsDCS increased MEP amplitudes indicating enhanced inhibitory GABA(A)ergic drive, while anodal tsDCS had the opposite effect, suggesting tsDCS could be a promising rehabilitation strategy for patients with acute brain lesions or spinal diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal Direct Current Stimulation Modulates Short Intracortical Inhibition. Bocci, T., Barloscio, D., Vergari, M., et al.[2022]

Transcutaneous spinal cord stimulation (TSS) significantly affects brain activity, activating key areas related to movement control and planning, as shown by EEG analysis in five participants performing lower-limb tasks.

TSS resulted in notable changes in functional connectivity in the brain during stimulation, unlike functional electrical stimulation (FES), suggesting TSS may be more effective for enhancing cortical engagement in rehabilitation strategies for spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of transcutaneous spinal stimulation on spatiotemporal cortical activation patterns: a proof-of-concept EEG study. Steele, AG., Manson, GA., Horner, PJ., et al.[2022]

Transcutaneous electrical stimulation of the spinal cord (TESS) significantly enhances motor-evoked potentials in arm muscles for up to 75 minutes after stimulation, indicating its potential to promote functional recovery in individuals with spinal cord injury (SCI).

The study found that TESS has a dual effect: it excites spinal networks while inhibiting cortical activity, which may contribute to improved hand and arm function, especially when using a specific 5 kHz carrier frequency during stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical and Subcortical Effects of Transcutaneous Spinal Cord Stimulation in Humans with Tetraplegia. Benavides, FD., Jo, HJ., Lundell, H., et al.[2021]

References

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

Model-Based Optimization of Spinal Cord Stimulation for Inspiratory Muscle Activation. [2022]

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

Transcutaneous Electrical Spinal Cord Stimulation to Promote Recovery in Chronic Spinal Cord Injury. [2022]

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

Transcutaneous Spinal Cord Stimulation and Motor Rehabilitation in Spinal Cord Injury: A Systematic Review. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Intercostal muscle pacing with high frequency spinal cord stimulation in dogs. [2021]

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

High-frequency spinal cord stimulation as rescue therapy for chronic pain patients with failure of conventional spinal cord stimulation. [2021]

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

Transcutaneous spinal cord stimulation and motor responses in individuals with spinal cord injury: A methodological review. [2022]

7. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Spinal direct current stimulation with locomotor training in chronic spinal cord injury. [2021]

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

Spinal Direct Current Stimulation Modulates Short Intracortical Inhibition. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Effects of transcutaneous spinal stimulation on spatiotemporal cortical activation patterns: a proof-of-concept EEG study. [2022]

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

Cortical and Subcortical Effects of Transcutaneous Spinal Cord Stimulation in Humans with Tetraplegia. [2021]