Trial record 14 of 161 for:    Cerebral Hypoxia

Lactate Therapy After Traumatic Brain Injury (LS_TCC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by Centre Hospitalier Universitaire Vaudois
Sponsor:
Collaborators:
Swiss National Science Foundation
European Society of Intensive Care Medicine
Information provided by (Responsible Party):
Mauro ODDO, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier:
NCT01573507
First received: April 1, 2012
Last updated: September 10, 2012
Last verified: September 2012
  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

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire Vaudois:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01573507

Contacts
Contact: Mauro Oddo, MD (+41)795561246 mauro.oddo@chuv.ch

Locations
Switzerland
CHUV, Lausanne University Hospital Recruiting
Lausanne, Switzerland, 1011
Contact: Mauro Oddo, MD    (+41)795561246    mauro.oddo@chuv.ch   
Principal Investigator: Mauro Oddo, MD         
Sponsors and Collaborators
Centre Hospitalier Universitaire Vaudois
Swiss National Science Foundation
European Society of Intensive Care Medicine
Investigators
Principal Investigator: Mauro Oddo, MD CHUV, Lausanne University Hospital, Switzerland
  More Information

No publications provided by Centre Hospitalier Universitaire Vaudois

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 September 16, 2014