Acute Intermittent Hypoxia for Spinal Cord Injury

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Colorado, Boulder

Disqualifiers: Severe illness, Cardiovascular, Pregnancy, others

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

Compensation: Varies

Number of Visits: 7

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called acute intermittent hypoxia, which involves short periods of low oxygen levels, to determine if it can improve leg function in individuals with chronic, incomplete spinal cord injuries. Participants will experience these brief low oxygen periods, which researchers believe might enhance movement. The trial includes two groups: one will undergo the low oxygen treatment, while the other will receive normal oxygen levels for comparison. Individuals who have had a spinal cord injury for over a year and can take a step, even with assistance, might be suitable candidates. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new therapies for spinal cord injuries.

Will I have to stop taking my current medications?

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

What prior data suggests that acute intermittent hypoxia is safe for individuals with spinal cord injury?

Research has shown that acute intermittent hypoxia (AIH) is generally safe for people. Studies indicate that AIH is well-tolerated, with few participants dropping out, meaning most continue with the treatment. Specifically, briefly exposing participants to low oxygen levels, such as 9% oxygen, has proven safe for those with long-term conditions like traumatic brain injury. While AIH appears to improve functions like breathing and leg strength, researchers continue to study its full benefits and any possible effects on the heart and blood vessels. Overall, AIH seems to be a safe option worth considering. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using acute intermittent hypoxia (AIH) for spinal cord injury because it represents a novel approach compared to standard options like physical therapy and medications that focus on managing symptoms. AIH works by exposing participants to short bursts of low oxygen levels, which may stimulate neural plasticity and help the damaged spinal cord recover some function. This method could potentially enhance the body's natural repair mechanisms, offering a complementary or alternative strategy to existing treatments. Unlike conventional therapies that often require prolonged periods to show improvement, AIH might deliver noticeable results in a shorter timeframe, making it a promising area of research.

What evidence suggests that acute intermittent hypoxia is effective for spinal cord injury?

This trial will compare the effects of acute intermittent hypoxia (AIH) with a sham treatment. Studies have shown that short periods of low oxygen, known as AIH, can improve muscle strength in people with partial spinal cord injuries. Research also suggests that AIH might enhance arm and hand function and improve breathing in those with long-term spinal injuries. AIH briefly reduces oxygen levels, helping the body adapt and strengthen muscles. Although more research is needed, early findings are promising for aiding recovery in spinal cord injury patients. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for people aged 18-75 with chronic, incomplete spinal cord injuries between C2 and L5 levels or non-traumatic disorders like MS. They must be medically stable, over a year post-injury, and able to take one step unaided or with devices. Excluded are those with recent concussions, metal head implants/pacemakers, needle aversion, pregnancy plans, severe illnesses/pain, cardiovascular issues, untreated musculoskeletal problems or mental health conditions.

Inclusion Criteria

Medically stable with medical clearance from physician to participate

My spinal cord injury allows some movement and is between my neck and lower back.

My spinal cord injury is classified as AIS A-D or is due to a non-traumatic disorder.

Exclusion Criteria

Concussion within the last six months

Metal implants in the head, or pacemaker

Aversion to needles

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Baseline Assessment

Baseline measurements including MRI, 6-Minute Walk Test, and 10-Meter Walk Test are conducted

1 week

1 visit (in-person)

Treatment

Participants undergo 4 consecutive days of acute intermittent hypoxia or normoxia exposure

1 week

4 visits (in-person)

Follow-up

Participants are monitored for changes in biomarkers and functional tests after treatment

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Acute Intermittent Hypoxia

Trial Overview

The study investigates the effects of Acute Intermittent Hypoxia (AIH) on serum blood proteins and lower limb function in individuals with incomplete spinal cord injury. It aims to understand how AIH influences recovery mechanisms and physical capabilities in affected limbs.

How Is the Trial Designed?

Group I: AIH Group Experimental Treatment 1 Intervention

Participants will be exposed to 4 consecutive days of acute intermittent hypoxia (AIH): 15, 1.5 min episodes at 9% O2 alternating with 21% O2 at 1 min intervals.

Group II: SHAM Group Active Control 1 Intervention

Participants will be exposed to 4 consecutive days of normoxia: 15, 1.5 min episodes at 21% O2 alternating with 21% O2 at 1 min intervals.

Who Is Running the Clinical Trial?

University of Colorado, Boulder

Lead Sponsor

Trials

128

Recruited

29,600+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

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]

Acute intermittent hypoxia (AIH) significantly improved lower extremity muscle strength in adults with chronic incomplete spinal cord injury, with torque increasing by approximately 20% at 30 minutes and 30% at 60 minutes post-AIH.

Pretreatment with ibuprofen did not enhance the effects of AIH on muscle strength, indicating that while AIH is effective for improving leg strength, systemic inflammation management with ibuprofen may not be necessary for its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of acute intermittent hypoxia on motor function in individuals with chronic spinal cord injury following ibuprofen pretreatment: A pilot study. Lynch, M., Duffell, L., Sandhu, M., et al.[2018]

Repetitive acute intermittent hypoxia (AIH) for 12 weeks significantly improved forelimb reach-to-grasp performance in rats with chronic cervical spinal cord injury, showing sustained benefits even 12 weeks post-treatment.

While AIH enhanced specific motor functions related to reaching tasks, it did not impact other motor tasks like ladder walking or adhesive removal, indicating that the benefits of AIH are task-specific when combined with targeted training.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged acute intermittent hypoxia improves forelimb reach-to-grasp function in a rat model of chronic cervical spinal cord injury. Arnold, BM., Toosi, BM., Caine, S., et al.[2021]

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]

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]

Therapeutic acute intermittent hypoxia (tAIH) shows promise in improving both respiratory and non-respiratory motor functions in individuals with neuromuscular disorders, particularly those with chronic spinal cord injuries, as highlighted in recent workshops aimed at clinical translation.

Key recommendations for advancing tAIH include enhancing our understanding of its mechanisms, optimizing treatment protocols, identifying effective combinatorial therapies, and ensuring long-term safety, which are essential for its potential routine clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic acute intermittent hypoxia: A translational roadmap for spinal cord injury and neuromuscular disease. Vose, AK., Welch, JF., Nair, J., et al.[2023]

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]

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 (IH) is a promising and safe method to improve physical function in individuals with chronic spinal cord injury (SCI), offering a time-efficient alternative to traditional exercise rehabilitation.

IH involves brief sessions of low oxygen exposure followed by normal breathing, which has shown efficacy in enhancing health and physical function without the need for extensive resources or specialized training.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Acute Intermittent Hypoxia on Physical Function and Health Status in Humans with Spinal Cord Injury: A Brief Review. Astorino, TA., Harness, ET., White, AC.[2018]

Acute intermittent hypoxia has shown promise as a therapeutic strategy to improve respiratory function in individuals with cervical spinal cord injuries, based on studies that demonstrate its potential to induce neuroplasticity and functional recovery.

Research in animal models has laid the groundwork for exploring the effects of acute intermittent hypoxia in human clinical studies, highlighting its potential to restore breathing function after spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent hypoxia and respiratory recovery in pre-clinical rodent models of incomplete cervical spinal cord injury. Gonzalez-Rothi, EJ., Lee, KZ.[2021]

Citations

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Efficacy and time course of acute intermittent hypoxia effects in ...

These findings demonstrate the potential of AIH to improve upper-extremity function in persons with chronic SCI, although follow-up studies are needed to ...

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sciencedirect.com

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Effects of acute intermittent hypoxia on muscle strength in ...

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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 ...

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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% ...

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Daily intermittent hypoxia enhances walking after chronic ...

Spinal synaptic enhancement with acute intermittent hypoxia improves respiratory function after chronic cervical spinal cord injury. J Neurosci 2005;25:2925 ...

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The review indicates that acute intermittent hypoxia is safe and has good treatment adherence, with low drop-out rates for acute intermittent ...

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Safety and potential benefits of acute intermittent hypoxia ...

Conclusions AIH dosage as low as 9% O2 appears safe to use in chronic TBI, but its potential benefits remain to be investigated. Competing ...

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clinicaltrials.gov

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Acute Intermittent Hypoxia on Leg Function Following ...

Acute intermittent hypoxia (AIH) exposure will increase maximum voluntary leg strength in persons with incomplete cervical spinal cord injury (SCI); AIH ...

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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 ...