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
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 (SC...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Mary Ann Liebert
2023-11-01
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| Series: | Neurotrauma Reports |
| Subjects: | |
| Online Access: | https://www.liebertpub.com/doi/full/10.1089/NEUR.2023.0036 |
| _version_ | 1797346140150038528 |
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| author | William M. Muter Linda Mansson Christopher Tuthill Shreya Aalla Stella Barth Emily Evans Kelly McKenzie Sara Prokup Chen Yang Milap Sandhu W. Zev Rymer Victor R. Edgerton Parag Gad Gordon S. Mitchell Samuel S. Wu Guogen Shan Arun Jayaraman Randy D. Trumbower |
| author_facet | William M. Muter Linda Mansson Christopher Tuthill Shreya Aalla Stella Barth Emily Evans Kelly McKenzie Sara Prokup Chen Yang Milap Sandhu W. Zev Rymer Victor R. Edgerton Parag Gad Gordon S. Mitchell Samuel S. Wu Guogen Shan Arun Jayaraman Randy D. Trumbower |
| author_sort | William M. Muter |
| collection | DOAJ |
| description | 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.
Trial Registration: ClinicalTrials.gov, NCT05563103. |
| first_indexed | 2024-03-08T11:27:29Z |
| format | Article |
| id | doaj.art-0a3f11401c194636a3d7f372f6f8fbe7 |
| institution | Directory Open Access Journal |
| issn | 2689-288X |
| language | English |
| last_indexed | 2024-03-08T11:27:29Z |
| publishDate | 2023-11-01 |
| publisher | Mary Ann Liebert |
| record_format | Article |
| series | Neurotrauma Reports |
| spelling | doaj.art-0a3f11401c194636a3d7f372f6f8fbe72024-01-26T04:44:34ZengMary Ann LiebertNeurotrauma Reports2689-288X2023-11-014173675010.1089/NEUR.2023.0036A 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 TrialWilliam M. MuterLinda ManssonChristopher TuthillShreya AallaStella BarthEmily EvansKelly McKenzieSara ProkupChen YangMilap SandhuW. Zev RymerVictor R. EdgertonParag GadGordon S. MitchellSamuel S. WuGuogen ShanArun JayaramanRandy D. TrumbowerBrief 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. Trial Registration: ClinicalTrials.gov, NCT05563103.https://www.liebertpub.com/doi/full/10.1089/NEUR.2023.0036electrical stimulationhypoxianeurological rehabilitationneuromodulationplasticityspinal cord trauma |
| spellingShingle | William M. Muter Linda Mansson Christopher Tuthill Shreya Aalla Stella Barth Emily Evans Kelly McKenzie Sara Prokup Chen Yang Milap Sandhu W. Zev Rymer Victor R. Edgerton Parag Gad Gordon S. Mitchell Samuel S. Wu Guogen Shan Arun Jayaraman Randy D. Trumbower 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 Neurotrauma Reports electrical stimulation hypoxia neurological rehabilitation neuromodulation plasticity spinal cord trauma |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | electrical stimulation hypoxia neurological rehabilitation neuromodulation plasticity spinal cord trauma |
| url | https://www.liebertpub.com/doi/full/10.1089/NEUR.2023.0036 |
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