Intermittent Hypoxia + Upper Limb Training for Spinal Cord Injury

Overseen By Alexander Barrry

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Shirley Ryan AbilityLab

Disqualifiers: Congestive heart failure, Uncontrolled diabetes, Severe asthma, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

58 Participants Needed

Trial Summary

What is the purpose of this trial?

Currently, there are a variety of approaches utilized in attempts to improve upper extremity function, including: traditional therapy, neuroprostheses, botulinum toxin injections, or surgical interventions. In addition, regenerative and restorative therapies, such as: epidural stimulation, functional electrical stimulation, and stem cell therapies, show promise in animal models, but are not ready for clinical translation. Subsequently, there is a clear need to develop new strategies that can stimulate spinal plasticity and strengthen existing synaptic connections in order to maximize the benefits of training paradigms. This study proposes the examine the effects of Acute Intermittent Hypoxia (AIH) in combination with upper extremity training, over the course of a month, to evaluate changes in upper extremity function, dexterity, and ability to complete activities of daily living. The use of acute intermittent hypoxia (AIH) has been demonstrated, through human and animal studies, to be an effective way of increasing spinal motor excitability and strengthening residual synaptic connectivity. AIH utilizes short duration (\<2 min) exposures to reduced oxygen levels (\~10% inspired oxygen), with alternating exposures to air with normal oxygen levels (\~21% inspired oxygen). Previous publications demonstrate that AIH is a safe and effective intervention to modify motor function in individual with chronic incomplete spinal cord injuries. The use of AIH has been shown to influence the activation in musculature, within 60-120 minutes of administration. In addition, when coupling AIH with overground gait training, an increase in functional endurance, as evaluated through the 6 minute walk test, and gait speed, as evaluated through the 10 meter walk test, were demonstrated. In addition, the use of hypoxic training has been studied in healthy individuals and athletes; however, literature examining the effect of a single bout of AIH on performance is limited.

Will I have to stop taking my current medications?

Participants do not have to stop taking antispasticity medications to join the study. The protocol does not specify about other medications, so it's best to discuss with the study team.

What data supports the effectiveness of the treatment Intermittent Hypoxia + Upper Limb Training for Spinal Cord Injury?

Research shows that acute intermittent hypoxia (AIH), which involves brief exposure to low oxygen levels, can improve hand strength and function in people with chronic spinal cord injuries. A study found that a single AIH session enhanced grip and pinch strength, suggesting potential benefits for upper-extremity function. ^{1 2 3 4 5}

Is intermittent hypoxia safe for humans?

Research on intermittent hypoxia, often combined with specific training, shows it can improve motor function in people with spinal cord injuries. While these studies focus on effectiveness, they do not report significant safety concerns, suggesting it is generally safe for human use. ^{1 2 4 6 7}

How does the treatment of Intermittent Hypoxia + Upper Limb Training for Spinal Cord Injury differ from other treatments?

This treatment is unique because it combines intermittent hypoxia (brief exposure to low oxygen levels) with upper limb training to enhance neuroplasticity (the brain's ability to reorganize itself) and improve motor function in people with spinal cord injuries. Unlike other treatments, this approach specifically targets the enhancement of neural pathways to improve hand and arm function, which is not commonly addressed by standard therapies. ^{1 2 3 4 6}

Eligibility Criteria

This trial is for individuals with non-progressive spinal cord injuries at levels C1-T1, who have some hand muscle activation or can use a tenodesis grasp. They must be over 6 months post-injury, not severely anemic (hemoglobin ≥10g/dl), and have stable blood pressure. It's not suitable for those with certain medical conditions like uncontrolled hypertension or diabetes, severe respiratory issues, heart problems, pregnant women, or those on mechanical ventilation.

Inclusion Criteria

I can move my hand muscles or use my wrist to grasp.

I do not experience symptoms like dizziness or lightheadedness.

I can continue my antispasticity medications while in the study.

Exclusion Criteria

Concurrent participation in another research study or therapy services

I have a brain injury affecting my thinking or memory.

I do not have severe heart, lung, blood pressure, or diabetes issues.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo Acute Intermittent Hypoxia (AIH) in combination with upper extremity training to evaluate changes in upper extremity function, dexterity, and ability to complete activities of daily living

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Acute Intermittent Hypoxia
• Upper extremity training/Armeo Spring

Trial Overview The study tests the effect of Acute Intermittent Hypoxia (AIH) combined with upper limb training to improve arm function in spinal cord injury patients. AIH involves short exposures to low oxygen followed by normal air and has shown promise in enhancing motor function when paired with physical training.

Participant Groups

Group I: Acute Intermittent Hypoxia (AIH) treatment Active Control 1 Intervention

The mask will first provide a normoxic air (room air) mixture (FiO2 = 0.21) via the mask. The mask is designed to couple with a universal mask circuit connecting to the air mixture system. The purpose of the mask will be to minimize room air entrainment.

Group II: AIH in combination with upper extremity training Active Control 1 Intervention

The mask will first provide a normoxic air (room air) mixture (FiO2 = 0.21) via the mask. The mask is designed to couple with a universal mask circuit connecting to the air mixture system. The purpose of the mask will be to minimize room air entrainment. In addition to this upper extremity training will be given using an upper-limb robotic rehabilitation device.

Group III: Sham AIH therapy in combination with upper extremity training Active Control 1 Intervention

Sham hypoxia followed by upper extremity training will be given using an upper-limb robotic rehabilitation device (Armeo Spring®, Hocoma AG, Switzerland). Armeo Spring is a gravity support system based on an ergonomic arm exoskeleton with integrated springs.

Group IV: Sham AIH therapy Active Control 1 Intervention

Sham hypoxia

Who Is Running the Clinical Trial?

Shirley Ryan AbilityLab

Lead Sponsor

Trials

212

Recruited

17,900+

Findings from Research

Daily acute intermittent hypoxia (AIH) combined with hand opening practice significantly improved hand dexterity and function in all six participants with chronic cervical spinal cord injury, as evidenced by better scores on the Box and Block Test and reduced times on the Jebsen-Taylor Hand Function Test.

The study suggests that AIH may enhance the effectiveness of rehabilitation by promoting neural plasticity, but further research is needed to determine the optimal dosage, safety, and long-term effects of this intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of acute intermittent hypoxia on hand use after spinal cord trauma: A preliminary study. Trumbower, RD., Hayes, HB., Mitchell, GS., et al.[2022]

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 involved 35 participants with incomplete spinal cord injury, testing the effects of combined intermittent hypoxia and body weight-supported treadmill training over 4 weeks.

Results showed that while standing balance did not improve significantly, participants receiving intermittent hypoxia demonstrated significantly faster dynamic balance measures, indicating potential benefits for mobility in individuals with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Hypoxia and Locomotor Training Enhances Dynamic but Not Standing Balance in Patients With Incomplete Spinal Cord Injury. Navarrete-Opazo, A., Alcayaga, JJ., Sepúlveda, O., et al.[2018]

Inspiratory muscle training (IMT) was found to be feasible and safe for seven adult patients with acute complete cervical or thoracic spinal cord injuries, with all planned sessions successfully delivered without any adverse events.

Some participants showed improvements in lung function, with increases in maximal inspiratory pressure for four individuals and forced vital capacity for three, suggesting potential efficacy of IMT in enhancing respiratory function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inspiratory muscle training is feasible and safe for patients with acute spinal cord injury. McDonald, T., Stiller, K.[2020]

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) treatment, when combined with specific motor training, can enhance motor recovery in rats with incomplete spinal cord injuries, as evidenced by improved performance on a ladder-crossing task after 7 days of treatment starting 4 weeks post-injury.

However, AIH alone or in combination with non-specific training did not lead to improvements in other motor tasks, highlighting the importance of task-specific training for maximizing the benefits of AIH in promoting neural plasticity and recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed Intervention with Intermittent Hypoxia and Task Training Improves Forelimb Function in a Rat Model of Cervical Spinal Injury. Prosser-Loose, EJ., Hassan, A., Mitchell, GS., et al.[2015]

References

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

Effects of acute intermittent hypoxia on hand use after spinal cord trauma: A preliminary study. [2022]

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

Efficacy and time course of acute intermittent hypoxia effects in the upper extremities of people with cervical spinal cord injury. [2022]

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

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

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

Intermittent Hypoxia and Locomotor Training Enhances Dynamic but Not Standing Balance in Patients With Incomplete Spinal Cord Injury. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Inspiratory muscle training is feasible and safe for patients with acute spinal cord injury. [2020]

6. 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]

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

Delayed Intervention with Intermittent Hypoxia and Task Training Improves Forelimb Function in a Rat Model of Cervical Spinal Injury. [2015]