PMID- 31354055 OWN - NLM STAT- MEDLINE DCOM- 20210412 LR - 20230427 IS - 1557-9042 (Electronic) IS - 0897-7151 (Print) IS - 0897-7151 (Linking) VI - 37 IP - 1 DP - 2020 Jan 1 TI - Magnetic Resonance Imaging Pilot Study of Intravenous Glyburide in Traumatic Brain Injury. PG - 185-193 LID - 10.1089/neu.2019.6538 [doi] AB - 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. 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. FAU - Eisenberg, Howard M AU - Eisenberg HM AD - Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland. FAU - Shenton, Martha E AU - Shenton ME AD - Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. AD - Department of Research and Development, VA Boston Healthcare System, Brockton Division, Brockton, Massachusetts. FAU - Pasternak, Ofer AU - Pasternak O AD - Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Simard, J Marc AU - Simard JM AD - Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland. FAU - Okonkwo, David O AU - Okonkwo DO AD - Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. FAU - Aldrich, Christina AU - Aldrich C AD - Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland. FAU - He, Feng AU - He F AD - Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California. FAU - Jain, Sonia AU - Jain S AD - Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California. FAU - Hayman, Erik G AU - Hayman EG AD - Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland. LA - eng GR - R01 HL082517/HL/NHLBI NIH HHS/United States GR - R01 NS102589/NS/NINDS NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20190827 PL - United States TA - J Neurotrauma JT - Journal of neurotrauma JID - 8811626 RN - 0 (Neuroprotective Agents) RN - SX6K58TVWC (Glyburide) SB - IM MH - Adult MH - Brain Edema/diagnostic imaging/etiology/prevention & control MH - Brain Injuries, Traumatic/complications/*diagnostic imaging/*drug therapy MH - Cerebral Hemorrhage/diagnostic imaging/etiology/prevention & control MH - Double-Blind Method MH - Female MH - Glyburide/*administration & dosage MH - Humans MH - Image Interpretation, Computer-Assisted/methods MH - Infusions, Intravenous MH - Magnetic Resonance Imaging/methods MH - Male MH - Middle Aged MH - Neuroprotective Agents/administration & dosage MH - Pilot Projects MH - Young Adult PMC - PMC6921286 OTO - NOTNLM OT - MRI OT - SUR1 OT - TBI OT - contusion OT - edema OT - glyburide COIS- JMS holds a U.S. patent (7,285,574), "A novel non-selective cation channel in neural cells and methods for treating brain swelling." JMS is a member of the Board of Directors and holds shares in Remedy Pharmaceuticals, Inc. and is a paid consultant for Biogen. For all other authors, no competing financial interests exist. EDAT- 2019/07/30 06:00 MHDA- 2021/04/13 06:00 PMCR- 2019/12/11 CRDT- 2019/07/30 06:00 PHST- 2019/07/30 06:00 [pubmed] PHST- 2021/04/13 06:00 [medline] PHST- 2019/07/30 06:00 [entrez] PHST- 2019/12/11 00:00 [pmc-release] AID - 10.1089/neu.2019.6538 [pii] AID - 10.1089/neu.2019.6538 [doi] PST - ppublish SO - J Neurotrauma. 2020 Jan 1;37(1):185-193. doi: 10.1089/neu.2019.6538. Epub 2019 Aug 27.