Traumatic Brain InjuryLS_TCCNCT01573507
Lactate Therapy After Traumatic Brain Injury
A study testing sodium lactate infusion in people with Traumatic Brain Injury and Subarachnoid Hemorrhage, run by Centre Hospitalier Universitaire Vaudois at 1 site in Switzerland.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Traumatic Brain Injury, Subarachnoid Hemorrhage
- What is being tested?
- sodium lactate infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteSwitzerland
- Study dates
- Mar 2012to 18 Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients admitted to our intensive care unit (ICU) after severe TBI or poor-grade aneurysmal subarachnoid hemorrhage (SAH), defined by a post-resuscitation Glasgow Coma Scale (GCS) < 9
- Age 18-75 years
- Abnormal head CT-scan (Marshall grade ≥ 2 or Fisher >2)
- Intracranial pressure (ICP), PbtO2 and cerebral MD monitoring as part of standard care
Who cannot join
- Penetrating TBI
- non aneurysmal SAH
- Age < 18 or > 75 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Neuroprotective Role of Lactate Therapy in Humans With Traumatic Brain Injury
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).
Read more
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.
Read the 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.
- Conditions
- Traumatic Brain Injury, Subarachnoid Hemorrhage
- Being tested
- sodium lactate infusion
- Keywords
- traumatic brain injury, lactate, brain metabolism, cerebral microdialysis, subarachnoid hemorrhage, transcranial doppler
- Medical subject headings
- Brain Injuries, Traumatic, Subarachnoid Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sodium lactate infusionOther
3-6 hours continuous infusion of sodium lactate (20-40 mcg/kg/min)
| Study group | Role | What they receive |
|---|---|---|
| sodium lactate infusion | Experimental | Continuous i.v. infusion of Sodium Lactate (2'400 mOsmol/L) over 3 hours Receives: Other: sodium lactate infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Increase from baseline in brain extracellular lactate, pyruvate and glucose
Increase from baseline in brain extracellular lactate, pyruvate and glucose measured with intra-parenchymal cerebral microdialysis catheter
Measured: 6 hours
Secondary outcomes (6)
Increase from baseline in brain tissue PO2
Brain tissue PO2 will be measured with intra-parenchymal probes
Measured: 6 hours
Increase from baseline in cerebral perfusion pressure
Measured: 6 hours
Decrease from baseline in intracranial pressure
Measured: 6 hours
plasma sodium
Measured: 6 hours
plasma osmolality
Measured: 6 hours
mean CBF, measured by transcranial doppler
Measured: 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2012 (estimated)
- Study startMar 2012
- Primary completion18 Dec 2017
- Study completion18 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Hypertonic lactate
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire Vaudois
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation, European Society of Intensive Care Medicine
- Responsible party
- Principal investigator, Mauro ODDO, Centre Hospitalier Universitaire Vaudois
- Investigators
- Mauro Oddo, MD, Principal investigator, CHUV, Lausanne University Hospital, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01573507
- Sponsor's protocol ID
- 237/10
- Acronym
- LS_TCC
- Status last verified
- Sep 2021
- First submitted
- 1 Apr 2012
- Last updated
- 9 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Carteron L, Solari D, Patet C, Quintard H, Miroz JP, Bloch J, Daniel RT, Hirt L, Eckert P, Magistretti PJ, Oddo M. Hypertonic Lactate to Improve Cerebral Perfusion and Glucose Availability After Acute Brain Injury. Crit Care Med. 2018 Oct;46(10):1649-1655. doi: 10.1097/CCM.0000000000003274.
PubMed 29923931Bouzat 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.
PubMed 24477453
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuroprotective Role of Lactate Therapy in Humans With Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT01573507
- Acronym / sponsor ID
- LS_TCC / 237/10
- Conditions
- Traumatic Brain Injury, Subarachnoid Hemorrhage
- Keywords
- traumatic brain injury, lactate, brain metabolism, cerebral microdialysis, subarachnoid hemorrhage, transcranial doppler
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire VaudoisUniversity, hospital or other
- Collaborators
- Swiss National Science Foundation, European Society of Intensive Care Medicine
- Study start
- Mar 2012 (actual)
- Primary completion
- 18 Dec 2017 (actual)
- Study completion
- 18 Dec 2017 (actual)
- First posted
- 9 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Hypertonic lactate
| Arm | Type | Receives |
|---|---|---|
| sodium lactate infusion | Experimental | Other: sodium lactate infusionContinuous i.v. infusion of Sodium Lactate (2'400 mOsmol/L) over 3 hours |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients admitted to our intensive care unit (ICU) after severe TBI or poor-grade aneurysmal subarachnoid hemorrhage (SAH), defined by a post-resuscitation Glasgow Coma Scale (GCS) < 9
- Age 18-75 years
- Abnormal head CT-scan (Marshall grade ≥ 2 or Fisher >2)
- Intracranial pressure (ICP), PbtO2 and cerebral MD monitoring as part of standard care
Key exclusion criteria (7 listed)
- Penetrating TBI
- non aneurysmal SAH
- Age < 18 or > 75 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sodium lactate infusion3-6 hours continuous infusion of sodium lactate (20-40 mcg/kg/min) | Other | sodium lactate infusion |
Primary outcome
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
6 secondary outcomes
Increase from baseline in brain tissue PO2
Time frame: 6 hours
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2021.
- Derived from this study: PubMed 29923931Carteron L, Solari D, Patet C, Quintard H, Miroz JP, Bloch J, Daniel RT, Hirt L, Eckert P, Magistretti PJ, Oddo M. Hypertonic Lactate to Improve Cerebral Perfusion and Glucose Availability After Acute Brain Injury. Crit Care Med. 2018 Oct;46(10):1649-1655. doi: 10.1097/CCM.0000000000003274.
- Derived from this study: PubMed 24477453Bouzat 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mauro Oddo, MD principal investigator
CHUV, Lausanne University Hospital, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing sodium lactate infusion in people with Traumatic Brain Injury and Subarachnoid Hemorrhage, run by Centre Hospitalier Universitaire Vaudois at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Increase from baseline in brain extracellular lactate, pyruvate and glucose (time frame: 6 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01573507, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2021.