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

100 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to clarify mechanisms of acute intermittent hypoxia and to examine the effect on lower limb function in persons with chronic, incomplete spinal cord injury.

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 data supports the effectiveness of the treatment Acute Intermittent Hypoxia for Spinal Cord Injury?

Research shows that Acute Intermittent Hypoxia (AIH) can improve motor function in individuals with chronic spinal cord injury by enhancing spinal plasticity, which is the ability of the spinal cord to adapt and recover. Studies in animal models and humans have demonstrated that AIH can lead to sustained improvements in both respiratory and non-respiratory motor functions. ^{1 2 3 4 5}

Is acute intermittent hypoxia generally safe for humans?

Research on acute intermittent hypoxia (AIH) in humans, particularly those with spinal cord injuries, suggests it is generally safe, though individual responses can vary. Studies have shown AIH can enhance motor function and breathing, but more research is needed to fully understand its safety and effectiveness. ^{1 2 6 7 8}

How does the treatment Acute Intermittent Hypoxia differ from other treatments for spinal cord injury?

Acute Intermittent Hypoxia (AIH) is unique because it involves brief, repeated exposures to low oxygen levels, which can trigger neuroplasticity (the brain's ability to reorganize itself) and improve breathing function in people with spinal cord injuries. Unlike traditional exercise-based rehabilitation, AIH is a time-efficient and potentially more accessible approach to enhance physical function and respiratory capacity. ^{1 6 7 9 10}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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 (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]

References

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

Intermittent hypoxia and respiratory recovery in pre-clinical rodent models of incomplete cervical spinal cord injury. [2021]

2. England 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. [2018]

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

Tetraplegia is associated with increased hypoxic ventilatory response during nonrapid eye movement sleep. [2023]

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

Therapeutic acute intermittent hypoxia: A translational roadmap for spinal cord injury and neuromuscular disease. [2023]

5. United States 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. [2021]

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

Tetraplegia is associated with enhanced peripheral chemoreflex sensitivity and ventilatory long-term facilitation. [2022]

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

APOE4, Age & Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia. [2023]

8. England pubmed.ncbi.nlm.nih.gov

APOE4, Age, and Sex Regulate Respiratory Plasticity Elicited by Acute Intermittent Hypercapnic-Hypoxia. [2023]

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

Single-session effects of acute intermittent hypoxia on breathing function after human spinal cord injury. [2022]

10. United States 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. [2018]