Dose-response Study of Arginine Supplementation in Severe Sepsis

Sepsis Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01775020
• Other study ID #: MEC03-139.5
• Status: Completed
• Phase: Phase 0
• First received: January 21, 2013
• Last updated: January 28, 2013
• Start date: October 2003
• Est. completion date: May 2012

Study information

• Verified date: January 2013
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: May 2012
• Est. primary completion date: May 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Sepsis
• Septic Shock

Intervention

Dietary Supplement:
• L-arginine

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Novartis Medical Nutrition

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nitric oxide synthesis	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	No
Secondary	hemodynamics	Mean arterial pressure (MAP), pulmonary arterial pressure (PAP), cardiac output (CO), cardiac index (CI), heart rate (HR)	8 hours	Yes
Secondary	blood parameters	Blood gasses, electrolytes, glucose, insulin, amino acids, whole body protein and arginine metabolism	8 hours	No
Secondary	gastric perfusion	Regional (gastric) CO2 production measured with tonometry (PrCO2)	8 hours	No