Magnetic resonance imaging pilot study of intravenous glyburide in traumatic brain injury
JournalJournal of Neurotrauma
PublisherMary Ann Liebert Inc.
MetadataShow full item record
AbstractPre-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. Of the 28 subjects, 25 had Glasgow Coma Scale (GCS) scores of 6-10, and 14 had contusions. There were no differences in adverse events (AEs) or severe adverse events (ASEs) between groups. The magnetic resonance imaging (MRI) percent change at 72-168 h from screening/baseline was compared between the glyburide and placebo groups. Analysis of contusions (7 per group) showed that lesion volumes (hemorrhage plus edema) increased 1036% with placebo versus 136% with glyburide (p = 0.15), and that hemorrhage volumes increased 11.6% with placebo but decreased 29.6% with glyburide (p = 0.62). Three diffusion MRI measures of edema were quantified: mean diffusivity (MD), free water (FW), and tissue MD (MDt), corresponding to overall, extracellular, and intracellular water, respectively. The percent change with time for each measure was compared in lesions (n = 14) versus uninjured white matter (n = 24) in subjects receiving placebo (n = 20) or glyburide (n = 18). 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. Copyright Howard M. Eisenberg et al., 2019.
SponsorsThis study was funded by a grant to HME from the Department of Defense U.S. Army Medical Research and Materiel Command (W81XWH-08-2-0159), INTRuST, and by Remedy Pharmaceuticals, Inc.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85076953339&doi=10.1089%2fneu.2019.6538&partnerID=40&md5=f0068230593bdae2df5689cfc44f342c; http://hdl.handle.net/10713/11564
- Traumatic hemorrhagic brain injury: impact of location and resorption on cognitive outcome.
- Authors: Martin RM, Wright MJ, Lutkenhoff ES, Ellingson BM, Van Horn JD, Tubi M, Alger JR, McArthur DL, Vespa PM
- Issue date: 2017 Mar
- Glibenclamide Produces Region-Dependent Effects on Cerebral Edema in a Combined Injury Model of Traumatic Brain Injury and Hemorrhagic Shock in Mice.
- Authors: Jha RM, Molyneaux BJ, Jackson TC, Wallisch JS, Park SY, Poloyac S, Vagni VA, Janesko-Feldman KL, Hoshitsuki K, Minnigh MB, Kochanek PM
- Issue date: 2018 Sep 1
- Effects of Oral Glibenclamide on Brain Contusion Volume and Functional Outcome of Patients with Moderate and Severe Traumatic Brain Injuries: A Randomized Double-Blind Placebo-Controlled Clinical Trial.
- Authors: Khalili H, Derakhshan N, Niakan A, Ghaffarpasand F, Salehi M, Eshraghian H, Shakibafard A, Zahabi B
- Issue date: 2017 May
- Safety and efficacy of intravenous glyburide on brain swelling after large hemispheric infarction (GAMES-RP): a randomised, double-blind, placebo-controlled phase 2 trial.
- Authors: Sheth KN, Elm JJ, Molyneaux BJ, Hinson H, Beslow LA, Sze GK, Ostwaldt AC, Del Zoppo GJ, Simard JM, Jacobson S, Kimberly WT
- Issue date: 2016 Oct
- Glyburide is associated with attenuated vasogenic edema in stroke patients.
- Authors: Kimberly WT, Battey TW, Pham L, Wu O, Yoo AJ, Furie KL, Singhal AB, Elm JJ, Stern BJ, Sheth KN
- Issue date: 2014 Apr