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

Brain Injuries, Traumatic Clinical Trial

— ELI-TBI  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02776488
• Other study ID #: ELI TBI 1
• Status: Withdrawn
• Phase: Phase 2
• Start date: September 2020
• Est. completion date: June 2026

Study information

• Verified date: November 2021
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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 safety analysis of exogenous sodium lactate infusions in humans and have demonstrated proof of concept that these fuels alter brain metabolism. Animal TBI studies have demonstrated proof of concept for exogenous lactate and pyruvate. We will conduct a multicenter, adaptive design-based, proof of concept biomarker mechanistic safety study of exogenous sodium lactate. The preliminary goal is to determine if exogenous lactate infusion is safe and has a demonstrated effect on selected biomarkers.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Wounds and Injuries

Intervention

Drug:
• Sodium Lactate
Infusion of exogenous sodium lactate
• Placebo
Infusion of normal saline

Locations

Country	Name	City	State
United States	David Geffen School of Medicine at UCLA	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality within 30 days	Percentage mortality within 30 days	30 days