Combination Therapy for Spinal Cord Injury (BO2ST Trial)
Palo Alto (17 mi)Overseen byRandy Trumbower, PT, PhD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: N/A
Recruiting
Sponsor: Spaulding Rehabilitation Hospital
No Placebo Group
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.
Is the treatment Daily acute intermittent hypoxia, Walking + tSTIM a promising treatment for spinal cord injury?Yes, the treatment is promising because it combines low-oxygen breathing and spinal stimulation to improve walking speed, endurance, and balance in people with spinal cord injuries. Studies show that this combination can lead to faster and more lasting improvements in walking ability compared to using each method alone.12357
What safety data exists for combination therapy for spinal cord injury?The safety data for combination therapy involving acute intermittent hypoxia (AIH) and transcutaneous spinal stimulation (tSTIM) in spinal cord injury (SCI) patients includes monitoring of pain levels, spasticity, sleep behavior, cognition, and rates of systemic hypertension and autonomic dysreflexia. Clinical trials have shown that AIH, when combined with walking training, enhances walking recovery in SCI patients and is considered a safe therapeutic alternative. Ongoing research emphasizes the need for long-term safety assessments and optimization of AIH protocols to maximize benefits while ensuring safety.12467
What data supports the idea that Combination Therapy for Spinal Cord Injury is an effective treatment?The available research shows that Combination Therapy, which includes breathing low oxygen (intermittent hypoxia) and walking training, can improve walking speed and endurance in people with spinal cord injuries. For example, one study found that participants who received this therapy walked faster and longer distances compared to those who did not. Another study confirmed these findings, showing that the therapy helped maintain and even enhance walking improvements over several weeks. This suggests that the therapy is effective in helping people with spinal cord injuries regain better walking abilities.12357
Do I need to stop my current medications for the trial?The trial protocol does not specify if you need to stop taking your current medications. However, if you have an active implanted device or are receiving concurrent electrical stimulation, you may not be eligible to participate.
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 am between 18 and 70 years old.
My spinal cord injury is between my neck and upper back, but I can still feel or move parts of my body below the injury.
My spinal injury is not getting worse.
I have some feeling or movement below my spinal cord injury.
My spinal injury is not getting worse.
I can walk 10 meters on my own without help.
I am between 18 and 70 years old.
My spinal cord injury is between my neck and upper back, but I can still feel or move parts of my body below the injury.
My spinal injury is not getting worse.
I can walk 10 meters without help.
My injury occurred over a year ago, minimizing chances of natural recovery.
Exclusion Criteria
I do not have severe illness or pain that would interfere with the study.
My mental function test score is below 24.
I experience severe and repeated episodes of autonomic dysreflexia.
I have had serious heart or lung problems, including high blood pressure over 150.
I have had botulinum toxin injections in my leg muscles in the last 6 months.
I have had surgery to move tendons or nerves in my leg.
I am currently undergoing electrical stimulation therapy.
Treatment Details
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.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: AIH + Walking Training with transcutaneous spinal stimulation (WALKtSTIM)Experimental Treatment2 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 Group2 Interventions
Acute Intermittent Hypoxia will be used as a pretreatment before walking training paired with sham transcutaneous spinal cord stimulation.
Group III: Sham + WALKtSTIMPlacebo Group2 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
Spaulding Rehabilitation HospitalCambridge, MA
Shirley Ryan AbilityLabChicago, IL
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Who is running the clinical trial?
Spaulding Rehabilitation HospitalLead Sponsor
United States Department of DefenseCollaborator
Shirley Ryan AbilityLabCollaborator
References
Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. [2022]To test the hypothesis that daily acute intermittent hypoxia (dAIH) and dAIH combined with overground walking improve walking speed and endurance in persons with chronic incomplete spinal cord injury (iSCI).
Repetitive Intermittent Hypoxia and Locomotor Training Enhances Walking Function in Incomplete Spinal Cord Injury Subjects: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial. [2022]Incomplete spinal cord injuries (iSCI) leave spared synaptic pathways below the level of injury. Intermittent hypoxia (IH) elicits plasticity in the spinal cord and strengthens spared synaptic pathways, expressed as respiratory and somatic functional recovery in experimental animals and humans with iSCI. This study is a randomized, triple-blind, two-arm parallel clinical trial performed in Santiago, Chile. We compared the effects of a 4-week protocol of IH combined with body weight-supported treadmill training (BWSTT), with continuous normoxia (Nx) and BWSTT on 10-meter walk test (10MWT), 6-minute walk test (6MWT), and timed up and go (TUG) test in American Spinal Injury Association C and D individuals with iSCI. Subjects received daily IH (cycling 9%/21% O2 every 1.5 min, 15 cycles/day) or continuous Nx (21% O2) combined with 45 min BWSTT for 5 consecutive days, followed by IH/Nx 3 × per week (3 × wIH/Nx) for 3 additional weeks. Subjects were assessed at day 5, weekly from weeks 2-4, and at a 2-week follow-up. Daily IH plus BWSTT enhanced walking speed, expressed as decreased 10MWT time at day 5 versus baseline (IH: -10.2 ± 3.0 vs. Nx: -1.7 ± 1.7 sec, p = 0.006), and walking endurance expressed as increased 6MWT distance at day 5 versus baseline (IH: 43.0 ± 10.7 vs. Nx: 6.1 ± 3.4 m, p = 0.012), but not TUG time. Further, 3 × wIH maintained the daily IH-induced walking speed, and enhanced the daily IH-induced walking endurance, which is maintained up to the 2-week follow-up. We conclude that daily IH enhances walking recovery in subjects with iSCI, confirming previous findings. Moreover, 3 × wIH prolonged or enhanced daily IH-induced walking speed and endurance improvements, respectively, up to 5 weeks post-daily IH. Repetitive IH may be a safe and effective therapeutic alternative for persons with iSCI.
Daily acute intermittent hypoxia to improve walking function in persons with subacute spinal cord injury: a randomized clinical trial study protocol. [2020]Restoring community walking remains a highly valued goal for persons recovering from traumatic incomplete spinal cord injury (SCI). Recently, studies report that brief episodes of low-oxygen breathing (acute intermittent hypoxia, AIH) may serve as an effective plasticity-inducing primer that enhances the effects of walking therapy in persons with chronic (> 1 year) SCI. More persistent walking recovery may occur following repetitive (weeks) AIH treatment involving persons with more acute SCI, but this possibility remains unknown. Here we present our clinical trial protocol, designed to examine the distinct influences of repetitive AIH, with and without walking practice, on walking recovery in persons with sub-acute SCI (
Prolonged acute intermittent hypoxia improves forelimb reach-to-grasp function in a rat model of chronic cervical spinal cord injury. [2021]Repetitive acute intermittent hypoxia (AIH - brief, episodes of low inspired oxygen) elicits spinal motor plasticity, resulting in sustained improvements of respiratory and non-respiratory motor function in both animal models and humans with chronic spinal cord injury (SCI). We previously demonstrated that 7 days of AIH combined with task-specific training improves performance on a skilled locomotor task for at least 3 weeks post-treatment in rats with incomplete SCI. Here we investigated the effect of repetitive AIH administered for 12 wks on a forelimb reach-to-grasp task in a rat model of chronic, incomplete cervical SCI. In a replicated, sham-controlled, randomized and blinded study, male Spraque-Dawley rats were subject to partial hemisection at the 3rd cervical spinal segment, and exposed to daily AIH (10, 5 min episodes of 11% inspired O2; 5 min intervals of 21% O2) or sham normoxia (continuous 21% O2) for 7 days beginning 8 weeks post-injury. Treatments were then reduced to 4 daily treatments per week, and continued for 11 weeks. Performance on 2 pre-conditioned motor tasks, single pellet reaching and horizontal ladder walking, was recorded each week for up to 12 weeks after initiating treatment; performance on spontaneous adhesive removal was also tested. SCI significantly impaired reach-to-grasp task performance 8 weeks post-injury (pre-treatment). Daily AIH improved reaching success by the first week of treatment versus sham controls, and this difference was maintained at 12 weeks (p < 0.0001). Daily AIH did not affect step asymmetry or stride length during ladder walking or adhesive removal time. Thus, prolonged AIH combined with task-specific training improved forelimb reach-to-grasp function in rats with a chronic cervical hemisection, but not off-target motor tasks. This study further supports the idea that daily AIH improves limb function when combined with task-specific training.
Acute intermittent hypoxia as a potential adjuvant to improve walking following spinal cord injury: evidence, challenges, and future directions. [2022]The reacquisition and preservation of walking ability are highly valued goals in spinal cord injury (SCI) rehabilitation. Recurrent episodes of breathing low oxygen (i.e., acute intermittent hypoxia, AIH) is a potential therapy to promote walking recovery after incomplete SCI via endogenous mechanisms of neuroplasticity. Here, we report on the progress of AIH, alone or paired with other treatments, on walking recovery in persons with incomplete SCI. We evaluate the evidence of AIH as a therapy ready for clinical and home use and the real and perceived challenges that may interfere with this possibility.
Therapeutic acute intermittent hypoxia: A translational roadmap for spinal cord injury and neuromuscular disease. [2023]We review progress towards greater mechanistic understanding and clinical translation of a strategy to improve respiratory and non-respiratory motor function in people with neuromuscular disorders, therapeutic acute intermittent hypoxia (tAIH). In 2016 and 2020, workshops to create and update a "road map to clinical translation" were held to help guide future research and development of tAIH to restore movement in people living with chronic, incomplete spinal cord injuries. After briefly discussing the pioneering, non-targeted basic research inspiring this novel therapeutic approach, we then summarize workshop recommendations, emphasizing critical knowledge gaps, priorities for future research effort, and steps needed to accelerate progress as we evaluate the potential of tAIH for routine clinical use. Highlighted areas include: 1) greater mechanistic understanding, particularly in non-respiratory motor systems; 2) optimization of tAIH protocols to maximize benefits; 3) identification of combinatorial treatments that amplify plasticity or remove plasticity constraints, including task-specific training; 4) identification of biomarkers for individuals most/least likely to benefit from tAIH; 5) assessment of long-term tAIH safety; and 6) development of a simple, safe and effective device to administer tAIH in clinical and home settings. Finally, we update ongoing clinical trials and recent investigations of tAIH in SCI and other clinical disorders that compromise motor function, including ALS, multiple sclerosis, and stroke.
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]Brief episodes of low oxygen breathing (therapeutic acute intermittent hypoxia; tAIH) may serve as an effective plasticity-promoting primer to enhance the effects of transcutaneous spinal stimulation-enhanced walking therapy (WALKtSTIM) in persons with chronic (>1 year) spinal cord injury (SCI). Pre-clinical studies in rodents with SCI show that tAIH and WALKtSTIM therapies harness complementary mechanisms of plasticity to maximize walking recovery. Here, we present a multi-site clinical trial protocol designed to examine the influence of tAIH + WALKtSTIM on walking recovery in persons with chronic SCI. We hypothesize that daily (eight sessions, 2 weeks) tAIH + WALKtSTIM will elicit faster, more persistent improvements in walking recovery than either treatment alone. To test our hypothesis, we are conducting a placebo-controlled clinical trial on 60 SCI participants who randomly receive one of three interventions: tAIH + WALKtSTIM; Placebo + WALKtSTIM; and tAIH + WALKtSHAM. Participants receive daily tAIH (fifteen 90-sec episodes at 10% O2 with 60-sec intervals at 21% O2) or daily placebo (fifteen 90-sec episodes at 21% O2 with 60-sec intervals at 21% O2) before a 45-min session of WALKtSTIM or WALKtSHAM. Our primary outcome measures assess walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up and Go Test). For safety, we also measure pain levels, spasticity, sleep behavior, cognition, and rates of systemic hypertension and autonomic dysreflexia. Assessments occur before, during, and after sessions, as well as at 1, 4, and 8 weeks post-intervention. Results from this study extend our understanding of the functional benefits of tAIH priming by investigating its capacity to boost the neuromodulatory effects of transcutaneous spinal stimulation on restoring walking after SCI. Given that there is no known cure for SCI and no single treatment is sufficient to overcome walking deficits, there is a critical need for combinatorial treatments that accelerate and anchor walking gains in persons with lifelong SCI.