Optimized Therapy in Severe Traumatic Brain Injured Patients

Study Overview
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Brief Summary
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Severe traumatic brain injury is associated with life-threatening and incapacitating secondary injury. Contemporary therapeutic interventions are aimed at preventing and treating secondary damage. In this context, improved cerebral metabolism is an important target in modern neurointensive care. The main hypothesis is that continuous intravenous infusion of glutamyl-alanyl dipeptide restores disturbed brain metabolism following severe traumatic brain injury.

Detailed Description
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Patients suffering from severe traumatic brain injury and requiring multimodal neuromonitoring during pharmacological coma will receive alanyl-glutamine dipeptide (Dipeptiven) as part of standard clinical nutrition. In two groups of patients the influence of different duration of infusion (group 1: 24 hours; group 2: 5 days) will be investigated. For this, pharmacokinetic and pharmacodynamic parameters in plasma and brain are determined. Increased plasma glutamine and alanine in arterial and jugular venous plasma and in cerebral microdialysates are to reflect efficacy of Dipeptiven infusion. Plasma glutamate levels as well as changes in cerebral glutamate, lactate, lactate/pyruvate ratio, intracranial pressure, bispectral index electroencephalography will be measured to exclude potential adverse effects

Official Title
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Improvement of Therapy in Patients With Severe Traumatic Brain Injury: Differential Impact of Local and Systemic Changes and Routinely Applied Drugs

Conditions
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Traumatic Brain Injury, Coma

Intervention / Treatment
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* Drug: Dipeptiven


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: severe traumatic brain injury prolonged pharmacologic coma multimodal neuromonitoring (microdialysis, ptiO2) enteral nutrition Exclusion Criteria: patients anticipated to decease within 48 hours abdominal injury mass transfusion renal impairment hepatic impairment barbiturate coma parenteral nutrition weight below 50 kg weight above 100 kg

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dipeptiven<br>0.75 g/ kg/ d Dipeptiven ( L- alanine- L- glutamine; 82 mg/ ml L- alanine, 134.6 mg/ ml L- glutamine; Fresenius Kabi, Switzerland) continuous intravenous infusion | Drug: Dipeptiven<br>* two groups: group 1: continuous infusion for 24 hours group 2: continuous infusion for 5 days<br>* Other names: Dipeptamin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma glutamine levels | changes in plasma glutamine levels during and after infusion of alanyl-glutamine compared to baseline and intra-infusion values expressed in absolute (micromole/ liter) or relative (%) values | 2 to 7 days | 
| cerebral glutamine | changes in cerebral glutamine levels during and after infusion of alanyl-glutamine compared to baseline and intra-infusion values expressed in absolute (micromole/ liter) or relative (%) values | 2 to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cerebral lactate | changes in cerebral lactate and lactate/pyruvate ratio reflecting cerebral energetic deficit during and after infusion of alanyl-glutamine compared to baseline and intra-infusion values expressed in absolute (millimole/ liter) or relative (%) values | 2 to 7 days | 
| cerebral lactate to pyruvate ratio | changes in lactate/pyruvate ratio reflecting cerebral energetic deficit during and after infusion of alanyl-glutamine compared to baseline and intra-infusion values expressed in absolute (millimole/ liter) or relative (%) values | 2 to 7 days | 
| cerebral glutamate | changes in cerebral glutamate reflecting cerebral energetic deficit during and after infusion of alanyl-glutamine compared to baseline and intra-infusion values expressed in absolute (micromole/ liter) or relative (%) values | 2 to 7 days | 
| intracranial pressure | changes in intracranial pressure reflecting brain edema during and after infusion of alanyl-glutamine compared to baseline and intra-infusion values expressed in absolute (mm Hg) or relative (%) values | 2 to 7 days | 
| bispectral index electroencephalography | changes in bispectral index EEG reflecting neuronal activation during and after infusion of alanyl-glutamine compared to baseline and intra-infusion values expressed in absolute or relative (%) values | 2 to 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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traumatic brain injury, glutamine, microdialysis, metabolism