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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a special air mixture and electrical stimulation, combined with exercise, can improve muscle strength for breathing and hand function in individuals with paralysis from a spinal cord injury. Participants will breathe air with low oxygen and higher carbon dioxide levels (Acute Intermittent Hypercapnic Hypoxia) and receive non-invasive spinal electrical stimulation (Transcutaneous Spinal Cord Stimulation), along with strength training. The goal is to determine if this approach enhances muscle performance. Suitable candidates have a spinal cord injury affecting their breathing strength and have lived with this condition for at least 12 months. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance the quality of life for those with spinal cord injuries.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that acute intermittent hypercapnic hypoxia (AIHH) is generally safe. Participants reported improved control of their breathing muscles, with only a few side effects. Some studies noted increases in blood pressure, but more research is needed to understand this effect.

Transcutaneous spinal cord stimulation (tSCS) has also undergone safety studies. Research indicates it is safe for individuals with spinal cord injuries and has improved strength and function in upper body muscles without major issues.

Both treatments have been well-tolerated in past research, but monitoring for any changes or discomfort during the trial remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for spinal cord injury because they explore innovative approaches like Acute Intermittent Hypercapnic Hypoxia (AIHH) and transcutaneous spinal cord stimulation (tSCS). Unlike traditional rehabilitation methods that often focus solely on physical therapy, AIHH involves controlled exposure to high levels of carbon dioxide, which may enhance neural plasticity and improve motor function. Meanwhile, tSCS uses non-invasive electrical currents to stimulate the spinal cord, potentially enhancing strength and respiratory function. These methods offer a fresh perspective on recovery, aiming to boost natural healing processes in the body and possibly lead to faster and more effective rehabilitation outcomes.

What evidence suggests that this trial's treatments could be effective for spinal cord injury?

Research has shown that acute intermittent hypercapnic hypoxia (AIHH) can improve breathing muscle function by activating certain brain processes. Studies have found that AIHH strengthens muscles and increases activity in people with spinal cord injuries. In this trial, some participants will receive AIHH combined with transcutaneous spinal cord stimulation (tSCS), which has shown promise in helping people regain movement; specifically, 72% of participants in one study experienced significant improvements in arm and leg function. Other participants will receive variations of these treatments, including sham versions, to assess their effectiveness. Combining AIHH with tSCS might further improve breathing and hand strength in individuals with paralysis due to spinal cord injuries. ^{1 4 6 7 8}

Who Is on the Research Team?

Justine Dee, PT

Principal Investigator

Thomas Jefferson University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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) 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12232992/

Acute intermittent hypercapnic-hypoxia elicits central neural ... We demonstrate that AIHH elicits central neural mechanisms of respiratory motor plasticity and increases resting respiratory drive in awake humans.

2. journals.physiology.org journals.physiology.org/doi/10.1152/physiol.2024.39.S1.1340

Combined therapeutic acute intermittent hypercapnic ... Therapeutic acute intermittent hypoxia (tAIH) is simple, safe, and effective means of inducing respiratory motor plasticity and improving ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1569904824001514

Safety and effectiveness of acute intermittent hypoxia ... Acute intermittent hypoxia enhances strength, and modulates spatial distribution of muscle activation in persons with chronic incomplete spinal cord injury ...

4. withpower.com withpower.com/trial/acute-intermittent-hypoxia-for-spinal-cord-injury-d78b4

Acute Intermittent Hypoxia for Spinal Cord Injury Acute intermittent hypoxia (AIH) significantly improved lower extremity muscle strength in adults with chronic incomplete spinal cord injury, with torque ...

5. liebertpub.com liebertpub.com/doi/10.1089/neu.2023.0353

Cardiorespiratory Responses to Acute Intermittent Hypoxia ... On average, SpO2 decreased to 82% during hypoxic episodes, similar to that of previous studies of mild-to-moderate AIH in persons with SCI (Fig. 6). During ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07002437

Hypoxia Pathways for Early Recovery After Spinal Cord Injury The long-term objective of this line of work is to test the hypothesis that an acute intermittent hypoxia protocol (3, 5 min episodes, 9-13% ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12056581/

Cardiorespiratory Responses to Acute Intermittent Hypoxia in ... After spinal cord injury (SCI), cardiorespiratory control is impaired, threatening the regulation of arterial O2 and CO2 partial pressures and the transport of ...

8. physoc.onlinelibrary.wiley.com physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP288115

Acute intermittent hypercapnic hypoxia augments left ... Acute intermittent hypercapnic hypoxia (IHH) evokes persistent increases in vascular sympathetic activity and blood pressure.