Lactate Therapy After Traumatic Brain Injury (LS_TCC)
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|ClinicalTrials.gov Identifier: NCT01573507|
Recruitment Status : Recruiting
First Posted : April 9, 2012
Last Update Posted : December 6, 2016
Background: Although glucose is essential to cerebral function, abundant experimental and clinical evidence demonstrates that endogenously released lactate, rather than glucose, is the preferential energy substrate for the brain in conditions of stress and acute injury. In patients with severe Traumatic Brain Injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH) monitored with cerebral microdialysis and brain tissue oxygen (PbtO2), our preliminary data show that increased brain extracellular lactate is frequently observed. Our findings indicate that elevated brain lactate more often occurs in the absence of brain hypoxia/ischemia and is mainly the consequence of increased cerebral glycolysis, i.e. it occurs in association with high extracellular pyruvate. These data suggest that the primary source of elevated lactate is activated glycolysis and strongly support the concept that endogenously released lactate can be utilized by the injured human brain as energy substrate. They prompt further investigation to examine whether exogenous lactate supplementation can be a valuable neuroprotective strategy after TBI or SAH. Indeed, in animal models of brain injury, administration of exogenous lactate improves neuronal and cognitive recovery.
Hypothesis: The investigators test the hypothesis that lactate therapy, administered during the acute phase of TBI or SAH, might exercise neuroprotective actions by restoring brain energetics and improving brain tissue PO2 and cerebral blood flow (CBF).
Aim of the study: The aim of this single-center study is to examine the effect of sodium lactate infusion on cerebral extracellular metabolites, brain tissue PO2 and cerebral blood flow, measured with CT perfusion and transcranial doppler (TCD).
Design: Prospective phase II interventional study examining the effect of a continuous 3-6 hours infusion of sodium lactate (20-40 µmol/kg/min), administered within 48 hours from TBI or SAH, on cerebral extracellular glucose, pyruvate, glutamate, glycerol, PbtO2 and CBF.
|Condition or disease||Intervention/treatment||Phase|
|Traumatic Brain Injury Subarachnoid Hemorrhage||Other: sodium lactate infusion||Phase 2|
Study: Prospective, single-centre phase II interventional study. The study will take place at the Department of Intensive Care Medicine, Lausanne University Medical Center (Centre Hospitalier Universitaire Vaudois, CHUV), Lausanne, Switzerland.
Patients will be monitored with an intra-parenchymal monitoring system, consisting of ICP (Codman®, Integra Neurosciences), PbtO2 (Licox®, Integra Neurosciences) and cerebral microdialysis (CMA Microdialysis®) catheters, based on the protocol for management of TBI presently in use at our center.
Each patient will receive a continuous infusion of sodium lactate (composition: lactate 1'000 mmol/L, Na 1'000 mmol/L: concentration 20-40 µmol/kg/min) for 3-6 hours. Sodium lactate will be prepared locally by the Pharmacie Centrale, CHUV, Lausanne.
Each patient will serve as his/her internal control, and the effect of sodium lactate on all brain physiological variables measured will be anayzed before, during and at the end of sodium lactate infusion.
The main parameters of efficacy are increases of MD glucose, MD pyruvate, PbtO2, and CBF, during sodium lactate perfusion.
For both MD glucose and MD pyruvate, we fixed as the minimal detectable effect of sodium lactate infusion a 30% increase of glucose and pyruvate at the end of the study. To obtain a power of 0.8 with an alpha of 0.05, the number of patients required to complete the study is 33. We therefore plan to include 35 patients.
Statistical analysis: At each time-point (baseline, during perfusion, end of sodium lactate infusion), differences of mean MD glucose, lactate, pyruvate, PbtO2, CBF, Mean transit time, ICP, CPP will be analyzed. We will also examine the percentage time spent with abnormal values (MD glucose < 1 mmol/L, PbtO2 < 20 mm Hg, ICP > 20 mm Hg). Differences will be compared using ANOVA for repeated measures.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Neuroprotective Role of Lactate Therapy in Humans With Traumatic Brain Injury|
|Study Start Date :||March 2012|
|Estimated Primary Completion Date :||November 2017|
|Estimated Study Completion Date :||March 2018|
Experimental: sodium lactate infusion
Continuous i.v. infusion of Sodium Lactate (2'400 mOsmol/L) over 3 hours
Other: sodium lactate infusion
3-6 hours continuous infusion of sodium lactate (20-40 mcg/kg/min)
- Increase from baseline in brain extracellular lactate, pyruvate and glucose [ Time Frame: 6 hours ]Increase from baseline in brain extracellular lactate, pyruvate and glucose measured with intra-parenchymal cerebral microdialysis catheter
- Increase from baseline in brain tissue PO2 [ Time Frame: 6 hours ]Brain tissue PO2 will be measured with intra-parenchymal probes
- Increase from baseline in cerebral perfusion pressure [ Time Frame: 6 hours ]
- Decrease from baseline in intracranial pressure [ Time Frame: 6 hours ]
- plasma sodium [ Time Frame: 6 hours ]
- plasma osmolality [ Time Frame: 6 hours ]
- mean CBF, measured by transcranial doppler [ Time Frame: 6 hours ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01573507
|Contact: Mauro Oddo, MD||(+41)firstname.lastname@example.org|
|CHUV, Lausanne University Hospital||Recruiting|
|Lausanne, Switzerland, 1011|
|Contact: Mauro Oddo, MD (+41)795561246 email@example.com|
|Principal Investigator: Mauro Oddo, MD|
|Principal Investigator:||Mauro Oddo, MD||CHUV, Lausanne University Hospital, Switzerland|