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

NCT02776488 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: ELI TBI 1
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Brain Injuries, Traumatic

Keywords

brain trauma, metabolic therapy

Outcome Measures

Primary Outcomes (1)

• Mortality within 30 days

  Percentage mortality within 30 days

  30 days

Study Arms (2)

ELI Arm

EXPERIMENTAL

Infusion of exogenous sodium lactate as supplemental fuel within 48 hours of TBI

Drug: Sodium Lactate

Placebo

PLACEBO COMPARATOR

Placebo infusion of normal saline in Part 2 RCT

Drug: Placebo

Interventions

Sodium Lactate DRUG

Infusion of exogenous sodium lactate

ELI Arm

Placebo DRUG

Infusion of normal saline

Also known as: Normal saline

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients seen in the Medical Center Emergency Department
• Adult patients transferred to the Neurocritical Intensive Care Unit with a physician's diagnosis of brain injury.
• GCS 3-12

You may not qualify if:

• Pregnancy at time of injury
• History of diabetes mellitus
• History of hemodynamic instability
• Known terminal illness which alters brain functioning
• Diagnosed AIDS progressed to AIDS dementia
• Known history of chronic severe neurological disturbance
• Severe retardation
• Previous severe diminished mental capacity
• No command of either English or Spanish
• Arrest for a felony
• Active neurologic condition such as stroke, recent TBI
• metabolic disorder
• preexisting hyperlactatemia
• instability precluding experimental intervention

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

Related Publications (9)

• 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.

  PMID: 25594628 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.

  PMID: 25279664 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.

  PMID: 22610193 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.

  PMID: 15716852 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.

  PMID: 26814699 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.

  PMID: 20029449 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.

  PMID: 24789621 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.

  PMID: 24477453 BACKGROUND

• 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.

  PMID: 40229764 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Sodium Lactate; Saline Solution

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Lactates; Hydroxy Acids; Carboxylic Acids; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Paul Vespa, MD

  University of California Los Angeles, Department of Neurosurgery

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Dose ranging and then RCT

Study Record Dates

• First Submitted: May 13, 2016
• First Posted: May 18, 2016
• Study Start: September 1, 2020
• Primary Completion: December 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: November 15, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)