Journal of neurotrauma
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Journal of neurotrauma · Jan 2020
Randomized Controlled Trial Multicenter StudyAn MRI Pilot Study of Intravenous Glyburide in Traumatic Brain Injury.
Pre-clinical studies of traumatic brain injury (TBI) show that glyburide reduces edema and hemorrhagic progression of contusions. We conducted a small Phase II, three-institution, randomized placebo-controlled trial of subjects with TBI to assess the safety and efficacy of intravenous (IV) glyburide. Twenty-eight subjects were randomized and underwent a 72-h infusion of IV glyburide or placebo, beginning within 10 h of trauma. ⋯ For placebo, the percent change in lesions for all three measures was significantly different compared with uninjured white matter (analysis of variance [ANOVA], p < 0.02), consistent with worsening of edema in untreated contusions. In contrast, for glyburide, the percent change in lesions for all three measures was not significantly different compared with uninjured white matter. Further study of IV glyburide in contusion TBI is warranted.
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Journal of neurotrauma · Dec 2019
Randomized Controlled TrialCopenhagen Head Injury Ciclosporin (CHIC) study: A phase IIa safety, pharmacokinetics and biomarker study of ciclosporin in severe head injury patients.
Traumatic brain injury (TBI) contributes to almost one third of all trauma-related deaths, and those that survive often suffer from long-term physical and cognitive deficits. Ciclosporin (cyclosporine, cyclosporin A) has shown promising neuroprotective properties in pre-clinical TBI models. The Copenhagen Head Injury Ciclosporin (CHIC) study was initiated to establish the safety profile and pharmacokinetics of ciclosporin in patients with severe TBI, using a novel parenteral lipid emulsion formulation. ⋯ The four biomarkers, glial fibrillary acidic protein, neurofilament light, tau, and ubiquitin carboxy-terminal hydrolase L1, showed consistent trends to decrease during the 5-day treatment period, whereas the samples taken on the days after the treatment period showed higher values in the majority of patients. In conclusion, ciclosporin, as administered in this study, is safe and well tolerated. The study confirmed that ciclosporin is able to pass the blood-brain barrier in a TBI population and provided an initial biomarker-based signal of efficacy.
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Journal of neurotrauma · Oct 2019
Randomized Controlled Trial Multicenter StudyAssociation of Very Early Serum Levels of S100B, Glial Fibrillary Acidic Protein, Ubiquitin C-terminal Hydrolase-L1, and Spectrin Breakdown Product with Outcome in ProTECT III.
Rapid risk-stratification of patients with acute traumatic brain injury (TBI) would inform management decisions and prognostication. The objective of this serum biomarker study (Biomarkers of Injury and Outcome [BIO]-Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment [ProTECT]) was to test the hypothesis that serum biomarkers of structural brain injury, measured at a single, very early time-point, add value beyond relevant clinical covariates when predicting unfavorable outcome 6 months after moderate-to-severe acute TBI. BIO-ProTECT utilized prospectively collected samples obtained from subjects with moderate-to-severe TBI enrolled in the ProTECT III clinical trial of progesterone. ⋯ Compared with a model containing baseline patient variables/characteristics, inclusion of S100B and GFAP significantly improved prognostic capacity (p ≤ 0.05 both comparisons); conversely, UCH-L1 and SBDP did not. A final predictive model incorporating baseline patient variables/characteristics and biomarker data (S100B and GFAP) had the best prognostic capability (area under the curve [AUC] = 0.85, 95% confidence interval [CI]: CI 0.81-0.89). Very early measurements of brain-specific biomarkers are independently associated with 6-month outcome after moderate-to-severe TBI and enhance outcome prediction.
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Journal of neurotrauma · Sep 2019
Randomized Controlled TrialLow-Dose Testosterone and Evoked Resistance Exercise after Spinal Cord Injury on Cardio-Metabolic Risk Factors: An Open-Label Randomized Clinical Trial.
The purpose of the work is to investigate the effects of low-dose testosterone replacement therapy (TRT) and evoked resistance training (RT) on body composition and metabolic variables after spinal cord injury (SCI). Twenty-two individuals with chronic motor complete SCI (ages 18-50 years) were randomly assigned to either TRT+RT (n = 11) or TRT (n = 11) for 16 weeks following a 4 -week delayed entry period. TRT+RT men underwent twice weekly progressive RT using electrical stimulation with ankle weights. ⋯ IGFBP-3 increased (p = 0.0001) while IL-6 decreased (p = 0.039) following both interventions, and TRT+RT suppressed adiponectin (p = 0.024). TRT+RT resulted in an increase in LM and whole thigh and knee extensor muscle CSAs, with an increase in BMR and suppressed adiponectin. Low-dose TRT may mediate modest effects on visceral adipose tissue, Sg, IGFBP-3, and IL-6, independent of changes in LM.
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Journal of neurotrauma · Sep 2019
Randomized Controlled TrialExercise-induced alterations in sympathetic-somatomotor coupling in incomplete spinal cord injury.
The aim of this study was to understand how high- and low-intensity locomotor training (LT) affects sympathetic-somatomotor (SS) coupling in people with incomplete spinal cord injury (SCI). Proper coupling between sympathetic and somatomotor systems allows controlled regulation of cardiovascular responses to exercise. In people with SCI, altered connectivity between descending pathways and spinal segments impairs sympathetic and somatomotor coordination, which may have deleterious effects during exercise and limit rehabilitation outcomes. ⋯ Participants who completed high- versus low-LT exhibited significant decreases in reflex torques during triggered sympathetic activity (cold: -83 vs. 13%, p < 0.01; pain: -65 vs. 54%, p < 0.05; mental math: -43 vs. 41%; p < 0.05). Mean arterial pressure responses to sympathetic stimuli were slightly higher following high- versus low-LT (cold: 30 vs. -1.5%; pain: 6 vs. -12%; mental math: 5 vs. 7%), although differences were not statistically significant. These results suggest that high-LT may be advantageous to low-LT to improve SS coupling in people with incomplete SCI.