Journal of neurotrauma
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Journal of neurotrauma · Aug 2021
Randomized Controlled TrialA Randomized Controlled Trial of Local Delivery of a Rho-Inhibitor (VX-210) in Patients With Acute Traumatic Cervical Spinal Cord Injury.
Acute traumatic spinal cord injury (SCI) can result in severe, lifelong neurological deficits. After SCI, Rho activation contributes to collapse of axonal growth cones, failure of axonal regeneration, and neuronal loss. This randomized, double-blind, placebo-controlled phase 2b/3 study evaluated the efficacy and safety of Rho inhibitor VX-210 (9 mg) in patients after acute traumatic cervical SCI. ⋯ The pre-defined futility stopping rule was met, and the study was therefore ended prematurely. In the final analysis, the primary efficacy end-point was not met, with no statistically significant difference in change from baseline in upper-extremity motor score at 6 months after treatment between the VX-210 (9-mg) and placebo groups. This work opens the door to further improvements in the design and conduct of clinical trials in acute SCI.
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Journal of neurotrauma · Jul 2021
Randomized Controlled Trial Multicenter StudyProgesterone treatment does not decrease serum levels of biomarkers of glial and neuronal cell injury in moderate and severe TBI subjects: A secondary analysis of the Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment (ProTECT) III trial.
Early treatment of moderate/severe traumatic brain injury (TBI) with progesterone does not improve clinical outcomes. This is in contrast with findings from pre-clinical studies of progesterone in TBI. To understand the reasons for the negative clinical trial, we investigated whether progesterone treatment has the desired biological effect of decreasing brain cell death. ⋯ There was no statistically significant correlation between serum progesterone concentrations and biomarker values obtained at 24 and 48 h. When examined as a continuous variable, baseline biomarker levels did not modify the association between progesterone treatment and neurological outcome (p of interaction term >0.39 for all biomarkers). We conclude that progesterone treatment does not decrease levels of biomarkers of glial and neuronal cell death during the first 48 h post-injury.
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Journal of neurotrauma · Jul 2021
Randomized Controlled TrialSequential Expression of Chemokines in Chronic Subdural Hematoma Fluids after Trepanation Surgery.
Chronic subdural hematoma (CSDH) is considered an angiogenic and inflammatory disease. Chemokines attract leukocytes, and invading neutrophils and monocytes/macrophages play important roles in wound healing. However, no studies have been reported regarding changes in expression of chemokines in CSDH fluid after trepanation surgery. ⋯ Moreover, there were significant relationships among concentrations of IL-8, GRO-α, ENA-78, and MCP-1 during the surgery and on day 1. In CSDH fluids, chemokines that attract neutrophils, such as IL-8, GRO-α, ENA-78, and macrophage-attracting MCP-1, appear first after trepanation surgery, whereas lymphocyte-attracting IP-10 and eosinophil-attracting eotaxin-3 levels do not change within 1 day of surgery. These findings suggest that neutrophils and macrophages may play important roles in the healing process of CSDH at an early stage.
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Journal of neurotrauma · Jul 2021
Randomized Controlled Trial Multicenter StudyRivastigmine Transdermal Patch Treatment for Moderate to Severe Cognitive Impairment in Veterans with Traumatic Brain Injury (RiVET Study): A Randomized Clinical Trial.
Cognitive impairment is common in veterans with histories of traumatic brain injury (TBI). Cholinergic deficits have been hypothesized as contributors to this impairment. We report the effects of cholinesterase inhibitor rivastigmine transdermal patch treatment in veterans with TBI and post-traumatic memory impairment. ⋯ The most commonly observed adverse events were application site reactions. This trial provides the largest sample to date of veterans with TBI and post-traumatic memory deficits enrolled in a pharmacological trial. Trial Registration: clinicaltrials.gov Identifier: NCT01670526.
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Journal of neurotrauma · Jun 2021
Randomized Controlled Trial Multicenter StudyCerebrospinal fluid Sulfonylurea Receptor-1 is associated with intracranial pressure and outcome after pediatric TBI-an exploratory analysis of the Cool Kids Trial.
Sulfonylurea receptor-1 (SUR1) is recognized increasingly as a key contributor to cerebral edema, hemorrhage progression, and possibly neuronal death in multiple forms of acute brain injury. SUR1 inhibition may be protective and is actively undergoing evaluation in Phase-2/3 trials of traumatic brain injury (TBI) and stroke. In adult TBI, SUR1 expression is associated with intracranial hypertension and contusion expansion; its role in pediatric TBI remains unexplored. ⋯ Mean CSF SUR1 concentration was associated with ICP and outcome. These findings are distinct from our previous report in adults with severe TBI, where SUR1 was detected universally. SUR1 may be a viable therapeutic target in a subset of pediatric TBI, and further study is warranted.