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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a combination of low oxygen sessions (daily acute intermittent hypoxia), spinal cord stimulation, and walking training might help individuals with chronic spinal cord injuries improve their walking ability. Participants will be divided into groups to test different combinations of these treatments. The trial seeks participants who have had a spinal cord injury for over a year, retain some movement or sensation below the injury, and can walk short distances unassisted. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance rehabilitation strategies for spinal cord injuries.

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.

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

Studies have shown that short periods of low oxygen levels, known as acute intermittent hypoxia, are generally safe and well-tolerated. Participants in previous studies experienced only minor side effects like muscle pain, dizziness, or shortness of breath. These side effects were not severe and did not cause many participants to leave the studies.

Research also shows that combining walking exercises with transcutaneous spinal cord stimulation, a type of electrical therapy, is safe for people with spinal cord injuries. This combination has been tested in adults and found to be safe and practical. Participants usually manage the treatment well, and it has helped improve movement in some cases.

Overall, both treatments have safety records suggesting they are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the combination therapy for spinal cord injury because it explores innovative ways to enhance recovery. Unlike traditional rehabilitation methods like physical therapy and medications, this approach uses acute intermittent hypoxia (AIH) as a pretreatment to potentially boost the effectiveness of walking training. Additionally, the incorporation of transcutaneous spinal cord stimulation (tSTIM) offers a non-invasive way to stimulate the spinal cord, which might improve motor function more effectively than current treatments. By combining these novel elements, the treatment could provide significant improvements in mobility for 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 shows that daily sessions of acute intermittent hypoxia, which involves short periods of low oxygen, can help people with spinal cord injuries walk better. Studies have found that it can increase muscle strength and improve nerve pathways that aid in walking recovery. In this trial, some participants will receive acute intermittent hypoxia combined with walking training and sham transcutaneous spinal stimulation.

Additionally, combining walking exercises with transcutaneous spinal cord stimulation (tSTIM) has effectively improved walking speed and motor skills. This method uses small electrical signals sent through the skin to stimulate the spinal cord and has shown promising results for people with long-term spinal cord injuries. In this trial, other participants will receive walking training with actual tSTIM. Both treatments offer hope for better mobility for those affected. ^{5 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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

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: 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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

Citations

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

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 ...

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

Effects of acute intermittent hypoxia on muscle strength in ... AHI has a potential benefit in improving muscle strength post-SCI. •. Motor incomplete SCIs are more likely to benefit from the AIH intervention.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03071393

Intermittent Hypoxia to Enhance Motor Function After ... Recent evidence has shown that acute intermittent hypoxia can strengthen motor pathways after spinal cord injury, and enhance walking outcomes after walking ...

4. 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 ...

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

Acute Intermittent Hypoxia With High-Intensity Gait Training ... Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. Neurology. 2014;82:104–113. doi: 10.1212 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41117316/

Effect of acute intermittent hypoxia to enhance motor ... The review indicates that acute intermittent hypoxia is safe and has good treatment adherence, with low drop-out rates for acute intermittent ...

7. medrxiv.org medrxiv.org/content/10.1101/2025.09.24.25336487v1

Safety and potential benefits of acute intermittent hypoxia ... Safety and potential benefits of acute intermittent hypoxia ... spinal cord injury, stroke, multiple sclerosis and mild cognitive impairment.

8. 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 ...

9. 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% ...