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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of low oxygen sessions (daily acute intermittent hypoxia), spinal cord stimulation, and walking training can improve walking in individuals with long-term spinal cord injuries. Participants will receive either a real or sham (placebo) low oxygen treatment before their walking sessions. Ideal candidates have a stable, non-progressive spinal cord injury and can walk independently, even if slowly. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could enhance mobility for individuals with spinal cord injuries.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that short periods of low oxygen each day are generally safe and can improve nerve function. Monitoring heart health during this treatment remains important.

Studies on combining walking with electrical currents to stimulate the spinal cord suggest it can help people with spinal cord injuries walk better. This method has not reported major safety issues.

These treatments appear well-tolerated, but further research is needed to ensure safety for everyone. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the trial for low oxygen therapy in spinal cord injury because it explores a new way to enhance recovery using acute intermittent hypoxia (AIH). Unlike traditional therapies such as physical rehabilitation and medications that focus on minimizing symptoms, AIH aims to boost nerve plasticity, potentially improving motor function. This approach is unique because it pairs AIH with walking training and transcutaneous spinal cord stimulation, possibly accelerating recovery more effectively than current methods. By investigating these combined techniques, researchers hope to unlock new possibilities for enhancing mobility in individuals with spinal cord injuries.

What evidence suggests that this trial's treatments could be effective for improving walking function in people with chronic spinal cord injury?

Research has shown that a daily treatment called acute intermittent hypoxia (AIH), which participants in this trial may receive, can help people with spinal cord injuries (SCI) improve their walking ability. Studies have found that AIH strengthens muscles, especially in those who retain some movement. In this trial, AIH is combined with walking exercises and a technique called transcutaneous spinal cord stimulation (tSTIM) in one of the treatment arms, potentially enhancing walking skills further. Recent evidence suggests that this combination can lead to quicker improvements in walking speed. Overall, these treatments hold promise for helping people with long-term SCI recover. ^{2 6 7 8 9}

Who Is on the Research Team?

Randy Trumbower, PT, PhD

Principal Investigator

Harvard Medical School (HMS and HSDM)

Are You a Good Fit for This Trial?

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 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) 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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) 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]

Citations

1. bmcneurol.biomedcentral.com bmcneurol.biomedcentral.com/articles/10.1186/s12883-020-01851-9

Daily acute intermittent hypoxia to improve walking function in ... Our overarching hypothesis is that daily exposure (10 sessions, 2 weeks) to AIH will enhance walking recovery in ambulatory and non-ambulatory persons with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32641012/

Daily acute intermittent hypoxia to improve walking function ... Our overarching hypothesis is that daily exposure (10 sessions, 2 weeks) to AIH will enhance walking recovery in ambulatory and non-ambulatory persons with ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0020138325000713

Effects of acute intermittent hypoxia on muscle strength in ... AIH is a promising therapeutic modality for enhancing muscle strength post-SCI, specifically in patients with motor-incomplete injuries.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02632422

AIH-induced Walking Recovery After Subacute SCI The purpose of this study is to determine how mild breathing bouts of low oxygen may restore walking and leg strength in persons who have sustained a spinal ...

5. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.124.047261

Acute Intermittent Hypoxia With High-Intensity Gait Training ... The goal of this study was to evaluate the safety and efficacy of AIH+HIT versus HIT alone in individuals with chronic stroke.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7341658/

Daily acute intermittent hypoxia to improve walking function ... Outcomes from this study may provide new insight into ways to enhance walking recovery in persons with SCI. Trial registration. ClinicalTrials.

7. 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 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT07002437

Hypoxia Pathways for Early Recovery After Spinal Cord Injury The long-term objective of this line of work is to test the hypothesis that an acute intermittent hypoxia protocol (3, 5 min episodes, 9-13% ...

9. 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 ...