Brain Injuries, Traumatic
Conditions
Keywords
brain trauma, metabolic therapy
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.
Interventions
DRUGSodium Lactate
Infusion of exogenous sodium lactate
DRUGPlacebo
Infusion of normal saline
Sponsors
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Dose ranging and then RCT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality within 30 days | 30 days | Percentage mortality within 30 days |
Countries
United States
Outcome results
None listed