Traumatic Brain InjuryPhase 4NCT02130674
Optimized Therapy in Severe Traumatic Brain Injured Patients
A Phase 4 study testing Dipeptiven in people with Traumatic Brain Injury and Coma, run by University of Zurich at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Traumatic Brain Injury, Coma
- What is being tested?
- Dipeptiven
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jan 2005to Feb 2011
- Phase
- Phase 4
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- severe traumatic brain injury
- prolonged pharmacologic coma
- multimodal neuromonitoring (microdialysis, ptiO2)
- enteral nutrition
Who cannot join
- patients anticipated to decease within 48 hours
- abdominal injury
- mass transfusion
- renal impairment
- hepatic impairment
- barbiturate coma
Show all 9Show fewer
- parenteral nutrition
- weight below 50 kg
- weight above 100 kg
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Improvement of Therapy in Patients With Severe Traumatic Brain Injury: Differential Impact of Local and Systemic Changes and Routinely Applied Drugs
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.
Read the 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
- Conditions
- Traumatic Brain Injury, Coma
- Being tested
- Dipeptiven
- Keywords
- traumatic brain injury, glutamine, microdialysis, metabolism
- Medical subject headings
- Brain Injuries, Traumatic, Coma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DipeptivenDrug
Also called Dipeptamin
two groups: group 1: continuous infusion for 24 hours group 2: continuous infusion for 5 days
| Study group | Role | What they receive |
|---|---|---|
| Dipeptiven | Experimental | 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 Receives: Drug: Dipeptiven |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 2 to 7 days
Secondary outcomes (5)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 2 to 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2014 (estimated)
- Study startJan 2005
- Primary completionFeb 2011
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation, Fresenius Kabi, University Hospital, Zürich
- Responsible party
- Principal investigator, John Stover, University of Zurich
- Investigators
- John F Stover, MD, Principal investigator, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02130674
- Sponsor's protocol ID
- SNF 111782
- Other IDs
- SNF 111782
- Status last verified
- May 2014
- First submitted
- 26 Apr 2014
- Last updated
- 6 May 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 24992948
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improvement of Therapy in Patients With Severe Traumatic Brain Injury: Differential Impact of Local and Systemic Changes and Routinely Applied Drugs
- ClinicalTrials.gov ID
- NCT02130674
- Acronym / sponsor ID
- SNF 111782
- Conditions
- Traumatic Brain Injury, Coma
- Keywords
- traumatic brain injury, glutamine, microdialysis, metabolism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Collaborators
- Swiss National Science Foundation, Fresenius Kabi, University Hospital, Zürich
- Study start
- Jan 2005
- Primary completion
- Feb 2011 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 5 May 2014 (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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dipeptiven | Experimental | Drug: Dipeptiven0.75 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- severe traumatic brain injury
- prolonged pharmacologic coma
- multimodal neuromonitoring (microdialysis, ptiO2)
- enteral nutrition
Key exclusion criteria (9 listed)
- patients anticipated to decease within 48 hours
- abdominal injury
- mass transfusion
- renal impairment
- hepatic impairment
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 |
|---|---|---|
| DipeptivenAlso: Dipeptamintwo groups: group 1: continuous infusion for 24 hours group 2: continuous infusion for 5 days | Drug | Dipeptiven |
Primary outcome
plasma glutamine levels
Time frame: 2 to 7 days
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
cerebral glutamine
Time frame: 2 to 7 days
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
5 secondary outcomes
cerebral lactate
Time frame: 2 to 7 days
cerebral lactate to pyruvate ratio
Time frame: 2 to 7 days
cerebral glutamate
Time frame: 2 to 7 days
intracranial pressure
Time frame: 2 to 7 days
bispectral index electroencephalography
Time frame: 2 to 7 days
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 6 May 2014.
- Derived from this study: PubMed 24992948Nageli 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.
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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.
John F Stover, MD principal investigator
University of Zurich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dipeptiven in people with Traumatic Brain Injury and Coma, run by University of Zurich 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 9 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 6 May 2014. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
plasma glutamine levels (time frame: 2 to 7 days). The study lists 2 primary outcomes in all. 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 NCT02130674, which also lists 1 linked publication.
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 6 May 2014.