Exogenous Sodium Lactate Infusion in Traumatic Brain Injury (ELI-TBI)

Summary

Metabolic crisis is a state of energy insufficiency due to impaired mitochondrial function as indicated by cerebral microdialysis lactate/pyruvate ratio (LPR). We have performed preliminary mechanistic analysis of alternative fuels in humans and have demonstrated proof of concept that exogenous fuels alter brain metabolism. We will conduct a multicenter, adaptive design-based, proof of concept phase 2 safety study of candidate supplemental fuels in patients with severe traumatic brain injury to determine safety and efficacy.

Timeline

Start

2020-09

Primary completion

2025-12

Completion

2026-06

Publications

• Background Glenn TC, Martin NA, Horning MA, McArthur DL, Hovda DA, Vespa P, Brooks GA. Lactate: brain fuel in human traumatic brain injury: a comparison with normal healthy control subjects. J Neurotrauma. 2015 Jun 1;32(11):820-32. doi: 10.1089/neu.2014.3483. Epub 2015 Mar 31.
• Background Glenn TC, Martin NA, McArthur DL, Hovda DA, Vespa P, Johnson ML, Horning MA, Brooks GA. Endogenous Nutritive Support after Traumatic Brain Injury: Peripheral Lactate Production for Glucose Supply via Gluconeogenesis. J Neurotrauma. 2015 Jun 1;32(11):811-9. doi: 10.1089/neu.2014.3482. Epub 2015 Mar 11.
• Background Vespa P, McArthur DL, Stein N, Huang SC, Shao W, Filippou M, Etchepare M, Glenn T, Hovda DA. Tight glycemic control increases metabolic distress in traumatic brain injury: a randomized controlled within-subjects trial. Crit Care Med. 2012 Jun;40(6):1923-9. doi: 10.1097/CCM.0b013e31824e0fcc.
• Background Vespa P, Bergsneider M, Hattori N, Wu HM, Huang SC, Martin NA, Glenn TC, McArthur DL, Hovda DA. Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. J Cereb Blood Flow Metab. 2005 Jun;25(6):763-74. doi: 10.1038/sj.jcbfm.9600073.
• Background Vespa P, Tubi M, Claassen J, Buitrago-Blanco M, McArthur D, Velazquez AG, Tu B, Prins M, Nuwer M. Metabolic crisis occurs with seizures and periodic discharges after brain trauma. Ann Neurol. 2016 Apr;79(4):579-90. doi: 10.1002/ana.24606. Epub 2016 Feb 28.
• Background Xu Y, McArthur DL, Alger JR, Etchepare M, Hovda DA, Glenn TC, Huang S, Dinov I, Vespa PM. Early nonischemic oxidative metabolic dysfunction leads to chronic brain atrophy in traumatic brain injury. J Cereb Blood Flow Metab. 2010 Apr;30(4):883-94. doi: 10.1038/jcbfm.2009.263. Epub 2009 Dec 23.
• Background Bouzat P, Magistretti PJ, Oddo M. Hypertonic lactate and the injured brain: facts and the potential for positive clinical implications. Intensive Care Med. 2014 Jun;40(6):920-1. doi: 10.1007/s00134-014-3312-x. Epub 2014 May 1. No abstract available.
• Background Bouzat P, Sala N, Suys T, Zerlauth JB, Marques-Vidal P, Feihl F, Bloch J, Messerer M, Levivier M, Meuli R, Magistretti PJ, Oddo M. Cerebral metabolic effects of exogenous lactate supplementation on the injured human brain. Intensive Care Med. 2014 Mar;40(3):412-21. doi: 10.1007/s00134-013-3203-6. Epub 2014 Jan 30.
• Vespa P, Wolahan S, Buitrago-Blanco M, Real C, Ruiz-Tejeda J, McArthur DL, Chiang JN, Agoston D, Glenn TC. Exogenous lactate infusion (ELI) in traumatic brain injury: higher dose is better? Crit Care. 2025 Apr 14;29(1):153. doi: 10.1186/s13054-025-05374-y.

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