Repetitive Acute Intermittent Hypoxia for Spinal Cord Injury

Overseen By Monica Perez, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Shirley Ryan AbilityLab

Must not be taking: Antipsychotics, Tricyclic antidepressants

Disqualifiers: Pulmonary, Cardiovascular, Orthopedic, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a treatment called acute intermittent hypoxia (rAIH) can help individuals with long-term spinal cord injuries improve arm and leg movement. Participants will receive either the real rAIH treatment or a sham version, along with training. The trial is open to those who have had a spinal cord injury for at least six months and can move their wrists or grip with one hand. Individuals with ongoing heart or lung issues or other conditions may not qualify. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could enhance rehabilitation options for spinal cord injury patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking drugs that affect the central nervous system and lower the seizure threshold, like certain antipsychotics or tricyclic antidepressants.

What prior data suggests that this protocol is safe for spinal cord injury recovery?

Research has shown that repeated exposure to short periods of low oxygen (rAIH) is generally safe for people. Studies have found that rAIH can improve movement and strength in individuals with long-term spinal cord injuries.

One study found that rAIH can cause changes in the nervous system that support recovery. Although considered safe, researchers continue to study its effects on the heart and blood vessels. Overall, rAIH appears to be a promising method to enhance function after a spinal cord injury, with manageable safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of repetitive acute intermittent hypoxia (rAIH) for spinal cord injury because it offers a novel approach that differs from the typical physical therapy and medication regimens currently used. rAIH involves short bursts of low oxygen exposure, which can stimulate the body's natural repair mechanisms and potentially enhance nerve function. This technique could lead to improved outcomes by promoting neural plasticity and recovery in ways that current treatments don't address. Unlike traditional methods that primarily focus on symptom management, rAIH targets the underlying neural pathways, offering a promising complementary strategy for rehabilitation.

What evidence suggests that repeated exposure to acute Intermittent Hypoxia (rAIH) could be effective for spinal cord injury?

Research has shown that repeated exposure to short periods of low oxygen, known as acute intermittent hypoxia (rAIH), can improve limb function after a spinal cord injury. Studies indicate that rAIH increases endurance and strength, particularly in the affected limbs. This method involves brief periods of reduced oxygen, which helps the nervous system adjust and improve. In this trial, participants will receive either rAIH combined with training or a sham version of rAIH with training. For people with spinal cord injuries, this approach has shown promise in restoring movement in both arms and legs. Overall, rAIH appears to be a safe and effective way to aid recovery in those with long-term spinal cord injuries. ^{3 4 5 6 7}

Who Is on the Research Team?

Monica Perez, PhD

Principal Investigator

Shirley Ryan AbilityLab

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 with chronic spinal cord injury at or above L2, who can grip with one hand or move their wrist and ankle slightly. It's not for those with uncontrolled medical issues, recent heart problems, pregnancy, seizure history, certain medication use, previous brain injuries or conditions affecting the spine other than SCI.

Inclusion Criteria

My spinal cord injury is at or above the L2 level.

I can slightly move my toes upwards and bend my hip.

Right-handed (Only right-handed individuals will be accepted into this group because of the potential differences in the organization of the brain in right handed and left handed individuals)

Exclusion Criteria

You have a history of severe depression or psychosis, or ongoing problems with thinking clearly.

I do not have unmanaged lung, heart, or bone problems.

Your heart beats more than 120 times per minute when you are resting.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive repeated exposure to acute Intermittent Hypoxia (rAIH) and training by research staff

6-8 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Repeated exposure to acute Intermittent Hypoxia (rAIH)

Trial Overview The study tests whether repeated sessions of acute intermittent hypoxia (brief periods of low oxygen) combined with upper and lower limb training can improve limb function in people with long-term spinal cord injuries.

How Is the Trial Designed?

Group I: rAIH + training by research staff Active Control 3 Interventions

Participants will receive repeated exposure to acute Intermittent Hypoxia (rAIH) and training by research staff.

Group II: sham rAIH + training Placebo Group 3 Interventions

Participants will sham receive repeated exposure to acute Intermittent Hypoxia (rAIH) and training by the research staff.

Who Is Running the Clinical Trial?

Shirley Ryan AbilityLab

Lead Sponsor

Trials

212

Recruited

17,900+

U.S. Department of Education

Collaborator

Trials

87

Recruited

54,500+

Published Research Related to This Trial

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]

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]

A 4-week treatment combining intermittent hypoxia (IH) with body weight-supported treadmill training (BWSTT) significantly improved walking speed and endurance in individuals with incomplete spinal cord injuries (iSCI), as shown by better performance on the 10-meter walk test and 6-minute walk test.

The benefits of daily IH were maintained with a reduced frequency of treatment (3 times a week), suggesting that IH could be a safe and effective long-term therapy to enhance recovery in individuals with iSCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Intermittent Hypoxia and Locomotor Training Enhances Walking Function in Incomplete Spinal Cord Injury Subjects: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial. Navarrete-Opazo, A., Alcayaga, J., Sepúlveda, O., et al.[2022]

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]

Acute intermittent hypoxia (AIH) can enhance traditional therapies for neurological dysfunction by promoting neuroplasticity and functional recovery, particularly in breathing and limb function after spinal cord injuries.

Carefully controlled repeated AIH (rAIH) is considered a safe and noninvasive treatment that can be effectively combined with physical therapy and other neurorehabilitative strategies, without causing harmful side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent hypoxia and neurorehabilitation. Gonzalez-Rothi, EJ., Lee, KZ., Dale, EA., et al.[2018]

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]

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]

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/PMC4475712/

Efficacy of Acute Intermittent Hypoxia on Physical Function ... Preliminary data from our facility have demonstrated a marked increase in aerobic endurance in response to IH administered immediately prior to completion of ...

2. 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 ...

3. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.124.046620

Acute Intermittent Hypoxia in People Living With Chronic ... AIH is potentially safe and effective for improving strength in the more-affected limb in people living with hemiparetic stroke.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT07002437

Hypoxia Pathways for Early Recovery After Spinal Cord Injury Acute intermittent hypoxia (AIH) - repetitive exposure to brief episodes of low inspired oxygen - is a promising strategy to restore ...

5. neurology.org neurology.org/doi/10.1212/01.WNL.0000437416.34298.43

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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4605870/

Repetitive Acute Intermittent Hypoxia Does Not Promote ... Modest protocols of repetitive acute intermittent hypoxia (rAIH) enhance motor function in patients with chronic incomplete spinal injury.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03433599

Repetitive Acute Intermittent Hypoxia for Spinal Cord ... Our goal is to enhance repeated exposure to acute intermittent hypoxia (rAIH)/training-induced aftereffects on upper and lower limb function recovery in humans ...