Combination Therapy for Spinal Cord Injury

(BO2ST Trial)

Recruiting at 1 trial location

Overseen By Arun Jayaraman, 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)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 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.

Do I need to stop my current medications for the trial?

The trial information 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 Combination Therapy for Spinal Cord Injury?

Research shows that brief episodes of low oxygen breathing, known as acute intermittent hypoxia (AIH), can enhance walking recovery in people with spinal cord injuries by promoting changes in the spinal cord that improve walking speed and endurance. Combining AIH with walking therapy and transcutaneous spinal stimulation (tSTIM) may lead to faster and more lasting improvements in walking ability. ^{1 2 3 4 5}

Is the combination therapy for spinal cord injury safe for humans?

The combination therapy involving intermittent hypoxia and walking training has been studied in humans with spinal cord injuries, and safety measures such as monitoring pain, spasticity, sleep behavior, cognition, and blood pressure were included in the trials. Repetitive intermittent hypoxia is considered a potentially safe therapeutic alternative for improving walking function in individuals with incomplete spinal cord injuries. ^{1 3 4 6 7}

How is the treatment for spinal cord injury using daily acute intermittent hypoxia and walking with tSTIM different from other treatments?

This treatment is unique because it combines brief episodes of low-oxygen breathing (acute intermittent hypoxia) with transcutaneous spinal stimulation and walking training to enhance walking recovery in people with spinal cord injuries. This combination aims to promote neuroplasticity (the brain's ability to reorganize itself) and improve walking function more effectively than either treatment alone. ^{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 adults aged 18-70 with chronic spinal cord injury (SCI) that's non-progressive and occurred over a year ago. Participants must be able to walk 10 meters without help, have some preserved sensory or motor function below the injury level, and score C-D on the ASIA scale. Pregnant individuals, those with active implants like baclofen pumps, recent botulinum toxin injections in legs, severe concurrent illnesses or certain surgeries are excluded.

Inclusion Criteria

I can walk 10 meters on my own without help.

You have experienced a brain or spinal cord injury more than a year ago, so that any natural recovery has already occurred.

My doctor has approved my participation in this study.

Exclusion Criteria

I experience severe and repeated episodes of autonomic dysreflexia.

I do not have severe illness or pain that would interfere with the study.

I have had serious heart or lung problems, including high blood pressure over 150.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a combination of acute intermittent hypoxia, transcutaneous spinal cord stimulation, and walking training to improve walking function

12 weeks

Regular visits for treatment sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Daily acute intermittent hypoxia
• Room air (SHAM)
• Walking + Sham transcutaneous spinal stimulation (tSHAM)
• Walking + tSTIM

Trial Overview The study tests if combining low oxygen levels (acute intermittent hypoxia), transcutaneous spinal stimulation (tSTIM), and walking training can improve walking in people with chronic SCI. It compares this combination therapy against sham interventions plus walking to see which is more effective.

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: AIH + Walking Training with sham transcutaneous spinal stimulation (WALKtSHAM) Placebo Group 2 Interventions

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

Group III: Sham + WALKtSTIM Placebo Group 2 Interventions

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+

Shirley Ryan AbilityLab

Collaborator

Trials

212

Recruited

17,900+

Findings from Research

Daily acute intermittent hypoxia (dAIH) significantly improved walking speed and endurance in individuals with chronic incomplete spinal cord injury, as shown by measurable improvements in the 10-Meter and 6-Minute Walk Tests after just one day of treatment.

Combining dAIH with overground walking further enhanced these benefits, indicating that this combination therapy could be a more effective approach for improving mobility in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. Hayes, HB., Jayaraman, A., Herrmann, M., 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]

A clinical trial is being conducted with 60 participants who have chronic spinal cord injuries to test the combined effects of therapeutic acute intermittent hypoxia (tAIH) and transcutaneous spinal stimulation (WALKtSTIM) on walking recovery, hypothesizing that this combination will lead to faster and more lasting improvements than either treatment alone.

The study will assess various outcomes related to walking ability, endurance, and balance, while also monitoring safety measures such as pain and spasticity, highlighting the need for effective combinatorial treatments for individuals with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Research Protocol to Study the Priming Effects of Breathing Low Oxygen on Enhancing Training-Related Gains in Walking Function for Persons With Spinal Cord Injury: The BO2ST Trial. Muter, WM., Mansson, L., Tuthill, C., 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]

This clinical trial will investigate the effects of daily acute intermittent hypoxia (AIH) on walking recovery in 85 participants with sub-acute spinal cord injury (SCI), aiming to determine if AIH can enhance recovery when combined with walking practice.

The study will assess various outcomes, including walking speed and endurance, while also monitoring safety measures like pain and spasticity, to evaluate the potential of AIH as a treatment to improve mobility in individuals with SCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily acute intermittent hypoxia to improve walking function in persons with subacute spinal cord injury: a randomized clinical trial study protocol. Naidu, A., Peters, DM., Tan, AQ., et al.[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]

Therapeutic acute intermittent hypoxia (tAIH) shows promise in improving both respiratory and non-respiratory motor functions in individuals with neuromuscular disorders, particularly those with chronic spinal cord injuries, as highlighted in recent workshops aimed at clinical translation.

Key recommendations for advancing tAIH include enhancing our understanding of its mechanisms, optimizing treatment protocols, identifying effective combinatorial therapies, and ensuring long-term safety, which are essential for its potential routine clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic acute intermittent hypoxia: A translational roadmap for spinal cord injury and neuromuscular disease. Vose, AK., Welch, JF., Nair, J., et al.[2023]

References

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

Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. [2022]

2. 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]

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

A Research Protocol to Study the Priming Effects of Breathing Low Oxygen on Enhancing Training-Related Gains in Walking Function for Persons With Spinal Cord Injury: The BO2ST Trial. [2023]

4. United States 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. [2022]

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

Daily acute intermittent hypoxia to improve walking function in persons with subacute spinal cord injury: a randomized clinical trial study protocol. [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

Therapeutic acute intermittent hypoxia: A translational roadmap for spinal cord injury and neuromuscular disease. [2023]