Clinical trial NCT02130674: Optimized Therapy in Severe Traumatic Brain Injured Patients
Official title: Improvement of Therapy in Patients With Severe Traumatic Brain Injury: Differential Impact of Local and Systemic Changes and Routinely Applied Drugs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Traumatic Brain Injury
Coma
Keywords: traumatic brain injury
glutamine
microdialysis
metabolism
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
name: Fresenius Kabi
name: University Hospital, Zürich
First posted: 2014-05-05
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: plasma glutamine levels
timeFrame: 2 to 7 days
measure: cerebral glutamine
timeFrame: 2 to 7 days
Secondary outcomes:
measure: cerebral lactate
timeFrame: 2 to 7 days
measure: cerebral lactate to pyruvate ratio
timeFrame: 2 to 7 days
measure: cerebral glutamate
timeFrame: 2 to 7 days
measure: intracranial pressure
timeFrame: 2 to 7 days
measure: bispectral index electroencephalography
timeFrame: 2 to 7 days
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: University of Zurich
name: John F Stover, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nageli M, Fasshauer M, Sommerfeld J, Fendel A, Brandi G, Stover JF. Prolonged continuous intravenous infusion of the dipeptide L-alanine- L-glutamine significantly increases plasma glutamine and alanine without elevating brain glutamate in patients with severe traumatic brain injury. Crit Care. 2014 Jul 2;18(4):R139. doi: 10.1186/cc13962.