- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01775020
Dose-response Study of Arginine Supplementation in Severe Sepsis
January 28, 2013 updated by: Maastricht University Medical Center
Arginine and Nitric Oxide (NO) Metabolism in Sepsis; Dose-response Study on the Effect of L-arginine Supplementation on NO Metabolism and Gastric Perfusion in Severe Septic Patients.
Pilot data in patients and data from pig studies indicate that arginine-NO metabolism is impaired in sepsis with changes in splanchnic metabolism and function, and reduced survival at low nitrate levels.
Prolonged intravenous supplementation of L-arginine proved effective in pigs for increasing NO production, restoring gut function, and inhibiting an increase in pulmonary arterial pressure, without any deleterious systemic side effects.
Prolonged intravenous L-arginine supplementation could therefore be useful in septic ICU patients.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
8
Phase
- Early Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Written informed consent from close relative
- Age > 18 years
- Patient meets the general criteria for severe sepsis or septic shock, diagnosed less than 48 h prior to study inclusion (see appendix A; in Dutch).
- Patient must be relatively hemodynamically stable, defined as stable blood pressure (variation in mean arterial pressure <15 mm Hg) during 2 h without necessity of increasing the vasopressor dose, inotropic support or rate of fluid administration.
- Systemic and pulmonary arterial catheters in place with continuous pressure monitoring.
- Patients in whom the clinician is prepared to provide full life support during the duration of the study, including a life expectance of > 24 h.
Exclusion Criteria:
- Shock due to any cause other than sepsis (e.g. drug reaction or drug overdose, pulmonary embolus, burn injury etc.)
- Corticosteroid use (prolonged intake of > 1mg/kg daily or intake of > 70 mg/day for 7 consecutive days within 1 month preceding the study)
- Liver cirrhosis
- Chronic pancreatitis
- Diabetes mellitus type I
- Metastases, haematological malignancies or chemotherapy
- Patients on dialysis (CVVH or other)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: L-arginine
|
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Nitric oxide synthesis
Time Frame: 8 hours
|
Nitric oxide synthesis at step-wise increasing doses of L-arginine infusion.
Following a 2h baseline measurements, 3 stepwise increasing arginine doses each provided for 2h will be tested for the effect on NO synthesis.
|
8 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
hemodynamics
Time Frame: 8 hours
|
Mean arterial pressure (MAP), pulmonary arterial pressure (PAP), cardiac output (CO), cardiac index (CI), heart rate (HR)
|
8 hours
|
blood parameters
Time Frame: 8 hours
|
Blood gasses, electrolytes, glucose, insulin, amino acids, whole body protein and arginine metabolism
|
8 hours
|
gastric perfusion
Time Frame: 8 hours
|
Regional (gastric) CO2 production measured with tonometry (PrCO2)
|
8 hours
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Nicolaas E Deutz, MD PhD
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Luiking YC, Poeze M, Ramsay G, Deutz NE. Reduced citrulline production in sepsis is related to diminished de novo arginine and nitric oxide production. Am J Clin Nutr. 2009 Jan;89(1):142-52. doi: 10.3945/ajcn.2007.25765. Epub 2008 Dec 3.
- Poeze M, Bruins MJ, Kessels F, Luiking YC, Lamers WH, Deutz NE. Effects of L-arginine pretreatment on nitric oxide metabolism and hepatosplanchnic perfusion during porcine endotoxemia. Am J Clin Nutr. 2011 Jun;93(6):1237-47. doi: 10.3945/ajcn.110.007237. Epub 2011 Apr 20.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2003
Primary Completion (Actual)
May 1, 2004
Study Completion (Actual)
May 1, 2012
Study Registration Dates
First Submitted
January 21, 2013
First Submitted That Met QC Criteria
January 21, 2013
First Posted (Estimate)
January 24, 2013
Study Record Updates
Last Update Posted (Estimate)
January 29, 2013
Last Update Submitted That Met QC Criteria
January 28, 2013
Last Verified
January 1, 2013
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MEC03-139.5
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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