{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T14:07:11Z","timestamp":1784902031098,"version":"3.55.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Spinal cord injury (SCI) often results in permanent paralysis, leading to substantial long-term disability and loss of quality-adjusted life years. Strategies to preserve neural function in the hyperacute phase are needed. Transcutaneous spinal cord stimulation (tSCS) improves neurological function in chronic SCI. Earlier implementation in acute SCI may preserve or restore function and improve recovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>STEP-RAISE is a Phase 1\/2 prospective clinical trial evaluating the safety and preliminary efficacy of tSCS in acute moderate-to-severe traumatic SCI. Electrical current will be delivered to the lumbosacral spinal cord using the investigational ARC-Ex device (ONWARD Medical) via surface electrodes over the thoracolumbar region. Phase 2 is a randomized, triple-blinded, placebo-controlled trial designed to assess treatment effects. Safety outcomes include hemodynamics, spinal cord perfusion pressure, and skin reactions. Efficacy will be assessed using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination with electromyography at baseline, during stimulation, and at 6-month follow-up. Biomarkers include neuronal (UCH-L1) and glial (GFAP) markers and exploratory proteomics in blood and cerebrospinal fluid collected prior to stimulation and at discharge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The STEP-RAISE trial evaluates safety and preliminary efficacy of non-invasive tSCS initiated within 72\u202fh of SCI to improve sensorimotor recovery. Neurophysiological and patient-reported outcomes will characterize recovery and assess whether early tSCS augments functional recovery. This study is designed to estimate treatment effects and inform subsequent trials in acute SCI. Planned enrollment includes 5 participants in Phase 1 and 10 in Phase 2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrial.gov: NCT07090473; first posted on 07\/29\/2025, first open to enrollment 04\/2026.\n                      <jats:ext-link>https:\/\/clinicaltrials.gov\/study\/NCT07090473<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1875365","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:53:10Z","timestamp":1784699590000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety of transcutaneous electrical stimulation potentiating recovery in acute spinal cord injury syndromes: a trial protocol"],"prefix":"10.3389","volume":"20","author":[{"given":"Anastasia","family":"Keller","sequence":"first","affiliation":[{"name":"Brain and Spinal Injury Research Center, Department of Neurological Surgery, University of California, San Francisco","place":["San Francisco, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakruthi Amar","family":"Kumar","sequence":"additional","affiliation":[{"name":"Brain and Spinal Injury Research Center, Department of Neurological Surgery, University of California, San Francisco","place":["San Francisco, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Bradfield","sequence":"additional","affiliation":[{"name":"Brain and Spinal Injury Research Center, Department of Neurological Surgery, University of California, San Francisco","place":["San Francisco, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra","family":"Hemmerle","sequence":"additional","affiliation":[{"name":"Brain and Spinal Injury Research Center, Department of Neurological Surgery, University of California, San Francisco","place":["San Francisco, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Russell","family":"Huie","sequence":"additional","affiliation":[{"name":"Brain and Spinal Injury Research Center, Department of Neurological Surgery, University of California, San Francisco","place":["San Francisco, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. E.","family":"Hinson","sequence":"additional","affiliation":[{"name":"Brain and Spinal Injury Research Center, Department of Neurological Surgery, University of California, San Francisco","place":["San Francisco, CA, United States"]},{"name":"Department of Neurology, University of California, San Francisco","place":["San Francisco, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Saigal","sequence":"additional","affiliation":[{"name":"Brain and Spinal Injury Research Center, Department of Neurological Surgery, University of California, San Francisco","place":["San Francisco, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"817","DOI":"10.3390\/children12070817","article-title":"Cumulative transcutaneous spinal stimulation with locomotor training safely improves trunk control in children with spinal cord injury: pilot study","volume":"12","author":"Amirova","year":"2025","journal-title":"Child. 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