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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help individuals with spinal cord injuries improve arm and hand function. It combines a breathing technique called Acute Intermittent Hypoxia (AIH), which involves short bursts of low oxygen, with upper limb training using the Armeo Spring device to enhance dexterity and daily living activities. Participants will be divided into groups to test AIH alone, AIH with training, sham (fake) AIH with training, or sham AIH alone. Suitable candidates have had a stable spinal cord injury for at least six months and can move their hands slightly or use a wrist extension grip. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative approach.

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 prior data suggests that this protocol is safe for improving upper extremity function in spinal cord injury?

Previous studies have shown that Acute Intermittent Hypoxia (AIH) is generally safe and effective for individuals with spinal cord injuries. AIH involves short periods of breathing air with reduced oxygen, which can improve movement abilities. Research indicates that AIH can enhance hand use and walking in these individuals. Importantly, studies on AIH for conditions like stroke and multiple sclerosis also support its safety.

When combined with arm exercises, AIH has shown promise in improving hand strength and skill. One study found that a single AIH session can boost grip and pinch strength, with the best effects appearing a few hours after treatment. While these results are promising, they come from early research stages focused on assessing safety and tolerance. This means the treatment has passed initial safety tests but requires further study to fully confirm its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for spinal cord injury because they explore the potential of combining intermittent hypoxia with upper limb robotic training. Unlike current treatment options, which often focus on physical therapy alone, this approach uses short bursts of low oxygen (intermittent hypoxia) to potentially stimulate nerve regeneration and enhance recovery. The Armeo Spring robotic device provides targeted, repetitive arm movements, which are crucial for rehabilitation. By combining these two methods, the treatments aim to maximize the recovery of arm function, offering a promising new direction for improving outcomes in spinal cord injury patients.

What evidence suggests that this trial's treatments could be effective for improving upper extremity function in spinal cord injury?

Research has shown that Acute Intermittent Hypoxia (AIH), a treatment in this trial, can improve movement in people with spinal cord injuries. Studies have found that a single AIH session can enhance grip and pinch strength, with optimal results appearing about 3 hours afterward. AIH temporarily reduces oxygen levels, which appears to activate the spinal cord and strengthen nerve connections. In this trial, some participants will receive AIH combined with upper extremity training, potentially boosting recovery further. This combination has shown promise in improving muscle strength and movement for people with spinal cord injuries. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 (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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03643770

Effect of a Novel Intervention Using Daily Intermittent ... 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 ...

2. withpower.com withpower.com/trial/intermittent-hypoxia-upper-limb-training-for-spinal-cord-injury-15a6f

Intermittent Hypoxia + Upper Limb Training for Spinal Cord ... 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8530358/

Efficacy and time course of acute intermittent hypoxia effects in ... We found that a single AIH session enhanced bilateral grip and pinch strength, and that this effect peaked ~3 hours post-intervention.

4. sralab.org sralab.org/clinical-trials/spinal-cord-injury/effect-novel-intervention-using-daily-intermittent-hypoxia-and-high-intensity-training-upper-limb

Effect of a Novel Intervention Using Daily Intermittent ... The use of acute intermittent hypoxia (AIH) has been demonstrated, to be an effective way of increasing spinal motor excitability and strengthening residual ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03644277

A Multi-Center Clinical Trial in Individuals With Spinal Cord ... The overall objective of this project is to investigate the effectiveness of daily acute intermittent hypoxia therapy (dAIH), coupled with massed practice ...

6. cdmrp.health.mil cdmrp.health.mil/scirp/research_highlights/20hypoxia_highlight

2020 Spinal Cord Injury Highlight - Acute Intermittent ... Acute intermittent hypoxia (AIH) holds tremendous promise in promoting walking, upper limb, bladder, and respiratory recovery in persons with SCI.

7. sralab.org sralab.org/clinical-trials/spinal-cord-injury/repetitive-acute-intermittent-hypoxia-spinal-cord-repair

Repetitive Acute Intermittent Hypoxia for Spinal Cord Repair This research is being conducted to study the effects of breathing low oxygen air (hypoxia) and exercise training on recovery of upper limb (arms and hands) ...