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Pre-clinical studies in rodents with SCI show that tAIH and WALK\n                    <jats:sub>tSTIM<\/jats:sub>\n                    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 + WALK\n                    <jats:sub>tSTIM<\/jats:sub>\n                    on walking recovery in persons with chronic SCI. We hypothesize that daily (eight sessions, 2 weeks) tAIH + WALK\n                    <jats:sub>tSTIM<\/jats:sub>\n                    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 + WALK\n                    <jats:sub>tSTIM<\/jats:sub>\n                    ; Placebo + WALK\n                    <jats:sub>tSTIM<\/jats:sub>\n                    ; and tAIH + WALK\n                    <jats:sub>tSHAM<\/jats:sub>\n                    . Participants receive daily tAIH (fifteen 90-sec episodes at 10% O\n                    <jats:sub>2<\/jats:sub>\n                    with 60-sec intervals at 21% O\n                    <jats:sub>2<\/jats:sub>\n                    ) or daily placebo (fifteen 90-sec episodes at 21% O\n                    <jats:sub>2<\/jats:sub>\n                    with 60-sec intervals at 21% O\n                    <jats:sub>2<\/jats:sub>\n                    ) before a 45-min session of WALK\n                    <jats:sub>tSTIM<\/jats:sub>\n                    or WALK\n                    <jats:sub>tSHAM<\/jats:sub>\n                    . 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.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>Trial Registration:<\/jats:title>\n                    <jats:p>ClinicalTrials.gov, NCT05563103.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/neur.2023.0036","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T10:29:29Z","timestamp":1699266569000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"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 BO\n                    <sub>2<\/sub>\n                    ST Trial"],"prefix":"10.1177","volume":"4","author":[{"given":"William M.","family":"Muter","sequence":"first","affiliation":[{"name":"Spaulding Rehabilitation Hospital, Charlestown, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Mansson","sequence":"additional","affiliation":[{"name":"Spaulding Rehabilitation Hospital, Charlestown, Massachusetts, USA."},{"name":"Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Tuthill","sequence":"additional","affiliation":[{"name":"Spaulding Rehabilitation Hospital, Charlestown, Massachusetts, USA."},{"name":"Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreya","family":"Aalla","sequence":"additional","affiliation":[{"name":"Shirley Ryan AbilityLab, Max Nader Center for Rehabilitation Technologies and Outcomes Research, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Barth","sequence":"additional","affiliation":[{"name":"Spaulding Rehabilitation Hospital, Charlestown, Massachusetts, USA."},{"name":"UMass Chan Medical School, University of Massachusetts, Worcester, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Boston University, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"McKenzie","sequence":"additional","affiliation":[{"name":"Shirley Ryan AbilityLab, Max Nader Center for Rehabilitation Technologies and Outcomes Research, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Prokup","sequence":"additional","affiliation":[{"name":"Shirley Ryan AbilityLab, Max Nader Center for Rehabilitation Technologies and Outcomes Research, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"Shirley Ryan AbilityLab, Max Nader Center for Rehabilitation Technologies and Outcomes Research, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milap","family":"Sandhu","sequence":"additional","affiliation":[{"name":"Shirley Ryan AbilityLab, Max Nader Center for Rehabilitation Technologies and Outcomes Research, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Zev","family":"Rymer","sequence":"additional","affiliation":[{"name":"Shirley Ryan AbilityLab, Max Nader Center for Rehabilitation Technologies and Outcomes Research, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor R.","family":"Edgerton","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of California\u2013Los Angeles, Los Angeles, California, USA."},{"name":"SpineX Inc., Northridge, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parag","family":"Gad","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of California\u2013Los Angeles, Los Angeles, California, USA."},{"name":"SpineX Inc., Northridge, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon S.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel S.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Florida, Gainesville, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guogen","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Florida, Gainesville, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Jayaraman","sequence":"additional","affiliation":[{"name":"Shirley Ryan AbilityLab, Max Nader Center for Rehabilitation Technologies and Outcomes Research, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy D.","family":"Trumbower","sequence":"additional","affiliation":[{"name":"Spaulding Rehabilitation Hospital, Charlestown, Massachusetts, USA."},{"name":"Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,11,6]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.sc.3102172"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1166"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0148-05.2005"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2021.113891"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2908-11.2012"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000437416.34298.43"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2016.4478"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2021.113669"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0192013"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu038"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0649-2"},{"key":"e_1_3_6_13_2","doi-asserted-by":"crossref","unstructured":"Gad P Gerasimenko Y Edgerton VR. 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