Lactate Therapy After Traumatic Brain Injury (LS_TCC)
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Purpose
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 severe Traumatic Brain Injury (TBI) patients 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. 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, 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.
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, on cerebral extracellular glucose, pyruvate, glutamate, glycerol, PbtO2 and CBF. A total of 35 patients will be required to complete the study.
| Condition | Intervention | Phase |
|---|---|---|
|
Traumatic Brain Injury |
Other: sodium lactate infusion |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Neuroprotective Role of Lactate Therapy in Humans With Traumatic Brain Injury |
- Increase from baseline in brain extracellular lactate, pyruvate and glucose [ Time Frame: 6 hours ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]Brain tissue PO2 will be measured with intra-parenchymal probes
- Increase from baseline in cerebral perfusion pressure [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
- Decrease from baseline in intracranial pressure [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
- Increase from baseline in mean transit time (MTT) [ Time Frame: 12 hours ] [ Designated as safety issue: No ]MTT will be calculated using brain CT perfusion
- plasma sodium [ Time Frame: 6 hours ] [ Designated as safety issue: Yes ]
- plasma osmolality [ Time Frame: 6 hours ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 30 |
| Study Start Date: | March 2012 |
| Estimated Study Completion Date: | March 2015 |
| Estimated Primary Completion Date: | March 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: sodium lactate infusion |
Other: sodium lactate infusion
3-6 hours continuous infusion of sodium lactate (20-40 mcg/kg/min)
|
Detailed Description:
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.
Patient population:
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.
Eligibility| Ages Eligible for Study: | 18 Years to 60 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients admitted to our intensive care unit (ICU) after severe TBI, defined by a post-resuscitation Glasgow Coma Scale (GCS) < 9
- Age 18-60 years
- Abnormal head CT-scan (Marshall grade ≥ 2)
- Intracranial pressure (ICP), PbtO2 and cerebral MD monitoring as part of standard care
Exclusion Criteria:
- Penetrating TBI
- Age < 18 or > 60 years,
- More than 1 extra-cranial injury with sustained hemodynamic instability and sustained blood lactate elevation > 4 mmol/L
- Cognitive handicap due to previous neurological or neurosurgical history
- Non-survivable injury, brain death or expected death within 48 hours
- Pregnancy
Contacts and Locations| Contact: Mauro Oddo, MD | (+41)795561246 | mauro.oddo@chuv.ch |
| Switzerland | |
| CHUV, Lausanne University Hospital | Recruiting |
| Lausanne, Switzerland, 1011 | |
| Contact: Mauro Oddo, MD (+41)795561246 mauro.oddo@chuv.ch | |
| Principal Investigator: Mauro Oddo, MD | |
| Principal Investigator: | Mauro Oddo, MD | CHUV, Lausanne University Hospital, Switzerland |
More Information
No publications provided
| Responsible Party: | Mauro ODDO, médecin adjoint, PD-MER I, Centre Hospitalier Universitaire Vaudois |
| ClinicalTrials.gov Identifier: | NCT01573507 History of Changes |
| Other Study ID Numbers: | 237/10 |
| Study First Received: | April 1, 2012 |
| Last Updated: | September 10, 2012 |
| Health Authority: | Switzerland: Swissmedic |
Keywords provided by Centre Hospitalier Universitaire Vaudois:
|
traumatic brain injury lactate brain metabolism cerebral microdialysis |
Additional relevant MeSH terms:
|
Brain Injuries Brain Diseases Central Nervous System Diseases Nervous System Diseases |
Craniocerebral Trauma Trauma, Nervous System Wounds and Injuries |
ClinicalTrials.gov processed this record on May 23, 2013