Low Oxygen Therapy for Spinal Cord Injury

(BO2ST-II Trial)

Recruiting at 1 trial location

Overseen By Randy Trumbower, PT, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Spaulding Rehabilitation Hospital

Must not be taking: Botulinum toxin

Disqualifiers: Severe illness, Hypertension, Pregnancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine how combining bouts of low oxygen, transcutaneous spinal cord stimulation, and walking training may improve walking function for people with chronic spinal cord injury of different age groups.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have an active implanted device or are receiving electrical stimulation, you may not be eligible to participate.

What data supports the effectiveness of the treatment Low Oxygen Therapy for Spinal Cord Injury?

Research shows that acute intermittent hypoxia (AIH), which involves brief episodes of low oxygen, can improve breathing and motor functions in both animal models and humans with spinal cord injury. Studies have demonstrated that AIH can enhance respiratory function and improve limb function when combined with task-specific training, suggesting its potential as a therapy for spinal cord injury recovery. ^{1 2 3 4 5}

Is Low Oxygen Therapy for Spinal Cord Injury safe for humans?

Research on acute intermittent hypoxia (AIH) suggests it is generally safe for humans, as studies have shown it can improve motor function in individuals with spinal cord injuries without significant adverse effects. However, individual responses can vary, and more research is needed to fully understand its safety profile. ^{1 2 5 6 7}

How does the treatment of acute intermittent hypoxia differ from other treatments for spinal cord injury?

Acute intermittent hypoxia (AIH) is unique because it involves brief, repeated exposure to low oxygen levels to promote neuroplasticity (the brain's ability to reorganize itself) and improve motor function after spinal cord injury. Unlike other treatments, AIH leverages the body's natural mechanisms to enhance recovery, potentially improving walking and breathing functions. ^{1 2 3 4 5}

Research Team

Randy Trumbower, PT, PhD

Principal Investigator

Harvard Medical School (HMS and HSDM)

Eligibility Criteria

This trial is for people aged 18-80 with chronic spinal cord injury who can walk a little without help. They should have some feeling or movement below the injury and be medically stable. It's not for those with severe pain, illness, heart or lung problems, pregnant women, or anyone using certain other treatments.

Inclusion Criteria

I can walk 10 meters on my own without help.

My injury is older than 12 months, reducing the chance of natural recovery.

Medically stable with medical clearance from study physician to participate

Exclusion Criteria

I do not have severe illness or pain, such as unhealed wounds, extreme nerve pain, serious infections, high blood pressure, heart or lung disease, very weak bones, bone growth in my legs, or intense inflammation.

My mental function score is below 24.

I am currently undergoing electrical stimulation therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo acute intermittent hypoxia (AIH) combined with transcutaneous spinal cord stimulation (tSTIM) and walking training

6 weeks

Multiple sessions per week

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Details

Interventions

• Daily acute intermittent hypoxia
• Walking + tSTIM

Trial Overview The study tests if low oxygen therapy (acute intermittent hypoxia), transcutaneous spinal cord stimulation (tSTIM), and walking training together can improve walking in people with long-term spinal injuries across different ages.

Participant Groups

Group I: AIH + Walking Training with transcutaneous spinal stimulation (WALKtSTIM) Experimental Treatment 2 Interventions

Acute Intermittent Hypoxia will be used as a pretreatment before walking training paired with transcutaneous spinal cord stimulation.

Group II: Sham + WALKtSTIM Placebo Group 1 Intervention

Sham acute intermittent hypoxia will be used as a pretreatment before walking training paired with transcutaneous spinal cord stimulation.

Daily acute intermittent hypoxia is already approved in United States for the following indications:

Approved in United States as Acute Intermittent Hypoxia for:

• Spinal Cord Injury Recovery
• Respiratory Function Improvement
• Walking Function Enhancement

Who Is Running the Clinical Trial?

Spaulding Rehabilitation Hospital

Lead Sponsor

Trials

143

Recruited

11,200+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Brooks Rehabilitation

Collaborator

Trials

16

Recruited

1,900+

Findings from Research

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]

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]

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) is a safe and effective therapy that can enhance strength, walking speed, endurance, and dynamic balance in individuals with chronic, incomplete spinal cord injury (SCI).

AIH shows promise for promoting walking recovery through neuroplasticity mechanisms, but more research is needed to determine its effectiveness across larger groups and to identify optimal treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute intermittent hypoxia as a potential adjuvant to improve walking following spinal cord injury: evidence, challenges, and future directions. Tan, AQ., Barth, S., Trumbower, RD.[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]

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]

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]

References

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

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

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

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

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

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

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

Acute intermittent hypoxia as a potential adjuvant to improve walking following spinal cord injury: evidence, challenges, and future directions. [2022]

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

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

7. 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]