Exogenous Sodium Lactate Infusion in Traumatic Brain Injury (ELI-TBI) (ELI-TBI)
Primary Purpose
Brain Injuries, Traumatic
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sodium Lactate
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Brain Injuries, Traumatic focused on measuring brain trauma, metabolic therapy
Eligibility Criteria
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
Sites / Locations
- David Geffen School of Medicine at UCLA
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ELI Arm
Placebo
Arm Description
Infusion of exogenous sodium lactate as supplemental fuel within 48 hours of TBI
Placebo infusion of normal saline in Part 2 RCT
Outcomes
Primary Outcome Measures
Mortality within 30 days
Percentage mortality within 30 days
Secondary Outcome Measures
Full Information
NCT ID
NCT02776488
First Posted
May 13, 2016
Last Updated
November 5, 2021
Sponsor
University of California, Los Angeles
1. Study Identification
Unique Protocol Identification Number
NCT02776488
Brief Title
Exogenous Sodium Lactate Infusion in Traumatic Brain Injury (ELI-TBI)
Acronym
ELI-TBI
Official Title
Exogenous Sodium Lactate Infusion in Traumatic Brain Injury (ELI-TBI)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Withdrawn
Why Stopped
The manufacturer of sodium lactate has stopped making the medication
Study Start Date
September 2020 (Anticipated)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
June 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Los Angeles
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Injuries, Traumatic
Keywords
brain trauma, metabolic therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Dose ranging and then RCT
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ELI Arm
Arm Type
Experimental
Arm Description
Infusion of exogenous sodium lactate as supplemental fuel within 48 hours of TBI
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo infusion of normal saline in Part 2 RCT
Intervention Type
Drug
Intervention Name(s)
Sodium Lactate
Intervention Description
Infusion of exogenous sodium lactate
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Normal saline
Intervention Description
Infusion of normal saline
Primary Outcome Measure Information:
Title
Mortality within 30 days
Description
Percentage mortality within 30 days
Time Frame
30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Vespa, MD
Organizational Affiliation
University of California Los Angeles, Department of Neurosurgery
Official's Role
Principal Investigator
Facility Information:
Facility Name
David Geffen School of Medicine at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
All protected health information (PHI) will be expunged from records before any sharing occurs
Citations:
PubMed Identifier
25594628
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.
Results Reference
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PubMed Identifier
25279664
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.
Results Reference
background
PubMed Identifier
22610193
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.
Results Reference
background
PubMed Identifier
15716852
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. doi: 10.1038/sj.jcbfm.9600073.
Results Reference
background
PubMed Identifier
26814699
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.
Results Reference
background
PubMed Identifier
20029449
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.
Results Reference
background
PubMed Identifier
24789621
Citation
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.
Results Reference
background
PubMed Identifier
24477453
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.
Results Reference
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Exogenous Sodium Lactate Infusion in Traumatic Brain Injury (ELI-TBI)
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