Abstract
Study designRetrospective, longitudinal analysis of motor and sensory outcomes following thoracic (T2–T12) sensorimotor complete spinal cord injury (SCI) in selected patients enrolled into three SCI) registries.ObjectivesTo establish a modern-day international benchmark for neurological recovery following traumatic complete thoracic sensorimotor SCI in a population similar to those enrolled in acute clinical trials.SettingAffiliates of the North American Clinical Trial Network (NACTN), European Multicenter Study about Spinal Cord Injury (EMSCI), and the Spinal Cord Injury Model Systems (SCIMS).MethodsOnly traumatic thoracic injured patients between 2006 and 2016 meeting commonly used clinical trial inclusion/exclusion criteria such as: age 16–70, T2–T12 neurological level of injury (NLI), ASIA Impairment Scale (AIS) A, non-penetrating injury, acute neurological exam within 7 days of injury, and follow-up neurological exam at least ~ 6 months post injury, were included in this analysis. International Standards for Neurological Classification of Spinal Cord injury outcomes including AIS conversion rate, NLI, and sensory and motor scores/levels were compiled.ResultsA total of 170 patients were included from the three registries: 12 from NACTN, 64 from EMSCI, and 94 from SCIMS. AIS conversion rates at approximately 6 months post injury varied from 16.7% to 23.4% (21.1% weighted average). Improved conversion rates were observed in all registries for low thoracic (T10–T12) injuries when compared with high/mid thoracic (T2–T9) injuries. The NLI was generally stable and lower extremity motor score (LEMS) improvement was uncommon and usually limited to low thoracic injuries only.ConclusionsThis study presents the aggregation of selected multinational natural history recovery data in thoracic AIS A patients from three SCI registries and demonstrates comparable minimal improvement of ISNCSCI-scored motor and sensory function following these injuries, whereas conversions to higher AIS grades occur at a frequency of ~20%. These data inform the development of future clinical trial protocols in this important patient population for the interpretation of the safety and potential clinical benefit of new therapies, and the potential applicability in a multinational setting.SponsorshipInVivo Therapeutics.
Highlights
Traumatic spinal cord injury (SCI) affects ~ 17,000 individuals each year in the United States [1], often resulting in significant impairments of motor, sensory, and autonomic functions as well as substantial financial burden
Multiple therapies intended to neuroprotect or repair the damaged spinal cord have been evaluated in clinical trials [2], yet, none have achieved regulatory approval for use in this patient population
The overall weighed average conversion percentage was calculated as North American Clinical Trials Network (NACTN) conversion % (12) + European Multicenter Study about Spinal Cord Injury (EMSCI) conversion % (64) + Spinal Cord Injury Model Systems (SCIMS) conversion % (75)/170
Summary
Traumatic spinal cord injury (SCI) affects ~ 17,000 individuals each year in the United States [1], often resulting in significant impairments of motor, sensory, and autonomic functions as well as substantial financial burden. One of the challenges facing clinical development of promising treatments for acute SCI is execution of clinical trials and interpretation of the results. The rare incidence of SCI, paucity of validated biomarkers and further patient segmentation based on inclusion/exclusion criteria leads to substantial challenges for trial enrollment and completion [3, 4]. In light of these issues, early-phase open-label clinical trials are typically conducted to assess both safety and preliminary effectiveness, interpretability of the results is often difficult. Future acute SCI clinical trial efficiencies are needed to safely and expeditiously advance the clinical development lifecycle of investigational treatments. Reliable imaging [8] or injury biomarkers from serum are in development [9] to more accurately stratify spinal cordinjured persons
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