Breathing Therapy for Spinal Cord Injury

Overseen By Hannah Snyder, M.S.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Florida

Must not be taking: Seizure threshold-lowering

Disqualifiers: Multiple sclerosis, Stroke, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 8

62 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a breathing technique called Acute Intermittent Hypoxia (AIH) to enhance breathing and motor function in individuals with spinal cord injuries. AIH involves short bursts of breathing low-oxygen air, with some sessions incorporating slightly higher carbon dioxide levels (Acute Intermittent Hypercapnic-Hypoxia, AIHH) for potentially better outcomes. Researchers aim to determine if AIHH is more effective than AIH alone and whether genetics influence individual responses. Individuals who have experienced a spinal cord injury for at least a year and have difficulty with breathing strength may be suitable candidates. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could improve treatment options for 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. However, if you are on medications that lower the seizure threshold, you may be excluded from certain parts of the study.

What prior data suggests that this breathing therapy is safe for spinal cord injury patients?

Studies have shown that both acute intermittent hypoxia (AIH) and acute intermittent hypercapnic-hypoxia (AIHH) are generally safe for humans. Research indicates that AIH is well-tolerated and can aid the nervous system in improving movement after a spinal cord injury. One study found that AIH, when combined with physical training, enhanced motor function without serious side effects.

Similarly, past research found AIHH, which involves slightly higher levels of carbon dioxide, to be safe. It also aids in improving breathing and movement skills. No severe adverse events were reported in the studies, though researchers recommend more monitoring of the heart and blood pressure during treatment. Overall, AIH and AIHH show promise in enhancing recovery after spinal cord injuries, with safety remaining a top priority in ongoing research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores innovative ways to improve breathing and respiratory strength in people with spinal cord injuries. Unlike standard treatments, which often focus on physical therapy or medications, this trial investigates the effects of Acute Intermittent Hypercapnic-Hypoxia (AIHH) and Acute Intermittent Hypoxia (AIH) through respiratory strength training and single-session testing. These methods aim to enhance breathing by exposing participants to controlled patterns of low oxygen and high carbon dioxide levels, potentially leading to faster and more effective respiratory improvement. Through this approach, researchers hope to uncover new strategies for enhancing respiratory function, ultimately improving the quality of life for individuals with spinal cord injuries.

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

Research has shown that acute intermittent hypoxia (AIH), a method participants in this trial may receive, can improve breathing and muscle strength in people with spinal cord injuries. Studies have found that AIH boosts movement abilities and aids recovery after an injury. Another treatment option in this trial is acute intermittent hypercapnic-hypoxia (AIHH), which involves adding a little extra carbon dioxide and might enhance these benefits. Animal studies suggest that AIHH can help restore lost breathing function. Both AIH and AIHH are considered safe, and participants tend to adhere to these treatments. Overall, these methods offer promising options for improving recovery after spinal cord injuries. ^{1 2 4 6 7}

Who Is on the Research Team?

Emily Fox

Principal Investigator

University of Florida & Brooks Rehabilitation

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with chronic spinal cord injury (SCI) at or below C-3 to T-12, who have had the condition for over a year and show some impairment in breathing strength. It's not open to those with other neurological conditions, severe pain, major illness, certain metal implants, or uncontrolled medical issues like hypertension.

Inclusion Criteria

Your ability to breathe in or out is 20% lower than normal.

Medically stable with physician clearance

I have some feeling or movement below my spinal injury.

Exclusion Criteria

I do not have severe illness or uncontrolled conditions like heart disease, lung disease, or high blood pressure.

I don't have seizures, uncontrolled migraines, a pacemaker, skull implants, or take seizure-lowering meds.

I experience severe and repeated episodes of autonomic dysreflexia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Single-session Testing Days

Participants complete baseline testing, receive AIH, AIHH, or sham AIH interventions, and undergo post-testing on three separate days.

3 days

3 visits (in-person)

Respiratory Strength Training Blocks

Participants undergo 5 days of AIH, AIHH, or sham AIH combined with respiratory strength training, followed by post-testing 1, 3, and 7 days after the intervention.

5 days of intervention + 7 days of follow-up

5 visits (in-person) for intervention, 3 visits (in-person) for follow-up

Follow-up

Participants are monitored for changes in maximal inspiratory and expiratory pressure, and motor evoked potential.

7 days

What Are the Treatments Tested in This Trial?

Interventions

• Acute Intermittent Hypercapnic-Hypoxia (AIHH)
• Acute Intermittent Hypoxia (AIH)
• Sham AIH

Trial Overview The study tests two types of breathing treatments: AIH which uses low oxygen air and AIHH that adds slightly more carbon dioxide. Participants will also do task-specific training. The goal is to see if these can improve respiratory function after SCI and if genetics affect the outcome.

How Is the Trial Designed?

Group I: Single-session testing days Experimental Treatment 3 Interventions

Participants will complete three separate single-session testing days. Baseline testing will be performed, then on each day, participants will receive AIH, AIHH, and sham AIH in random order. Post-testing will occur after each intervention.

Group II: Respiratory strength training blocks Experimental Treatment 3 Interventions

Participants will complete three separate respiratory strength training blocks. In each block, participants will receive 5 days of AIH, 5 days of AIHH, and 5 days of sham AIH in random order, followed by respiratory strength training. Each block will include 5 days of intervention and training, and post-testing 1, 3, and 7 days after intervention and training has concluded.

Acute Intermittent Hypercapnic-Hypoxia (AIHH) is already approved in United States, Canada for the following indications:

Approved in United States as Acute Intermittent Hypoxia (AIH) for:

• Respiratory recovery in spinal cord injury
• Improvement in motor function after spinal cord injury

Approved in Canada as Therapeutic Acute Intermittent Hypoxia for:

• Respiratory recovery in spinal cord injury

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

U.S. Army Medical Research Acquisition Activity

Collaborator

Trials

26

Recruited

10,500+

Published Research Related to This Trial

A single session of acute intermittent hypoxia (AIH) significantly increased maximal inspiratory pressure (MIP) in 17 adults with chronic spinal cord injury (SCI), suggesting potential for enhancing respiratory function.

While AIH improved MIP, other breathing functions like maximal expiratory pressure (MEP) and forced vital capacity (FVC) did not show significant changes, indicating that AIH may selectively affect certain respiratory muscles and highlighting the need for further research into its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-session effects of acute intermittent hypoxia on breathing function after human spinal cord injury. Sutor, T., Cavka, K., Vose, AK., et al.[2022]

Individuals with cervical spinal cord injury (SCI) showed a significantly higher short-term hypoxic ventilatory response (HVR) during acute intermittent hypoxia (AIH) compared to those with thoracic SCI, indicating a potentially different respiratory response mechanism in cervical SCI patients.

Despite the increased short-term HVR, there was no evidence of long-term ventilatory facilitation following AIH in either cervical or thoracic SCI groups, suggesting that while acute responses may differ, long-term adaptations in ventilation are not observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetraplegia is associated with increased hypoxic ventilatory response during nonrapid eye movement sleep. Vaughan, S., Sankari, A., Carroll, S., et al.[2023]

Acute intermittent hypoxia (AIH) is a safe and effective therapy that can enhance strength, walking speed, endurance, and dynamic balance in individuals with chronic, incomplete spinal cord injury (SCI).

AIH shows promise for promoting walking recovery through neuroplasticity mechanisms, but more research is needed to determine its effectiveness across larger groups and to identify optimal treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute intermittent hypoxia as a potential adjuvant to improve walking following spinal cord injury: evidence, challenges, and future directions. Tan, AQ., Barth, S., Trumbower, RD.[2022]

In a study of 17 healthy adults, it was found that individuals with the APOE4 genotype showed lower respiratory motor plasticity in response to acute intermittent hypercapnic-hypoxia (AIHH), suggesting genetic factors can influence the effectiveness of this rehabilitation strategy.

Additionally, males demonstrated greater improvements in diaphragm motor function compared to females, and older age was associated with reduced respiratory response, highlighting the importance of sex and age as biological determinants in AIHH outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

APOE4, Age, and Sex Regulate Respiratory Plasticity Elicited by Acute Intermittent Hypercapnic-Hypoxia. Nair, J., Welch, JF., Marciante, AB., et al.[2023]

Acute intermittent hypoxia (AIH) is a safe treatment that involves alternating between low and normal oxygen levels, but in this study, it did not significantly change the excitability of the primary motor cortex in healthy participants.

Despite a notable drop in arterial oxygen saturation during AIH, there were no measurable effects on corticospinal excitability or intracortical circuits, suggesting that AIH may need to be adjusted in severity or tailored to individuals for potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of acute intermittent hypoxia on corticospinal excitability within the primary motor cortex. Radia, S., Vallence, AM., Fujiyama, H., et al.[2022]

The study found that individuals with the APOE 4 genotype showed lower diaphragm motor-evoked potential (MEP) enhancements in response to acute intermittent hypercapnic-hypoxia (AIHH), indicating that genetic factors can influence the effectiveness of this rehabilitation strategy.

Additionally, the research revealed that males had a greater enhancement in diaphragm MEP compared to females, and that age negatively affected respiratory motor plasticity, highlighting the importance of biological factors in individual responses to AIHH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

APOE4, Age & Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia. Nair, J., Welch, JF., Marciante, AB., et al.[2023]

Patients with cervical spinal cord injury (SCI) showed significantly higher minute ventilation (V̇e) after acute intermittent hypoxia (AIH) compared to able-bodied controls, indicating a potential for enhanced respiratory recovery.

While heart rate variability responses to hypoxia were observed in all groups, individuals with cervical SCI did not exhibit the same recovery patterns as those with thoracic SCI or able-bodied individuals, suggesting unique cardiovascular responses in cervical SCI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetraplegia is associated with enhanced peripheral chemoreflex sensitivity and ventilatory long-term facilitation. Sankari, A., Bascom, AT., Riehani, A., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8820239/

Therapeutic acute intermittent hypoxia: a translational ... We now know that: “low dose” tAIH restores lost respiratory function in rats with acute (< 2 weeks) cervical spinal injuries (Lovett-Barr et al., 2012; ...

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

Combined therapeutic acute intermittent hypercapnic ... We focus on a refined tAIH protocol that combines hypoxia with hypercapnia during each episode (therapeutic acute intermittent hypercapnic ...

3. brooksrehab.org brooksrehab.org/resources/researchers-receive-grant-to-study-improved-breathing-for-sci/

Researchers Receive $3.6 Million Grant for Study to ... A new treatment known as therapeutic acute intermittent hypoxia (AIH) has shown promise for improving breathing ability in people living with chronic spinal ...

4. 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% ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0020138325000713

Effects of acute intermittent hypoxia on muscle strength in ... AIH is a promising therapeutic modality for enhancing muscle strength post-SCI, specifically in patients with motor-incomplete injuries.

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

Safety and effectiveness of acute intermittent hypoxia ... Acute intermittent hypoxia is generally safe and effective at producing neural plastic responses, but further examination of co-occurring cardiovascular ...

7. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.124.047261

Acute Intermittent Hypoxia With High-Intensity Gait Training ... The goal of this study was to evaluate the safety and efficacy of AIH+HIT versus HIT alone in individuals with chronic stroke.