L-citrulline Supplementation During Sepsis

Sepsis Clinical Trial

Official title:

Arginine and Nitric Oxide (NO) Metabolism in Sepsis; L-citrulline Enteral Supplementation for the Normalisation of the Arginine-NO Metabolism

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT00628381
• Other study ID #: MEC-08
• Secondary ID: ZON/NW 40-00806-
• Status: Not yet recruiting
• Phase: Phase 3
• First received: February 26, 2008
• Last updated: September 2, 2010
• Start date: January 2011
• Est. completion date: January 2013

Study information

• Verified date: September 2010
• Source: Maastricht University Medical Center
• Contact: Nina Wijnands, MD, PhD-student
• Phone: +31-43-3884502
• Email: n.wijnands[@]ah.unimaas.nl
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to study the stimulating effects of prolonged (8h) enteral L-citrulline supplementation on the normalisation of the plasma citrulline concentrations and the Arginine-NO metabolism, the microcirculation, the systemic hemodynamics, vascular permeability, and organ function and disease severity scores.

Description:

NO synthesis is compromised during sepsis through lack of arginine de novo synthesis and may thereby contribute to impaired microcirculation and organ dysfunction. Supplementation of L-citrulline in septic patients will increase NO production without increased arginase activity and these effects will be studied on arginine-NO metabolism,improved organ function, vascular permeability and microcirculation.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 48
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• 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.

• Patient must be relatively hemodynamically stable, defined as stable blood pressure (variation in mean arterial pressure <15 mm Hg) during 2h without necessity of increasing the vasopressor dose, inotropic support or rate of fluid administration.

• Systemic arterial catheter in place with continuous pressure monitoring.

• Patients in whom the clinician is prepared to provide full life support during the duration of the study

Exclusion Criteria:

• Shock due to any cause other than sepsis (e.g. drug reaction or drug overdose, pulmonary embolus, burn injury etc.)

• Prolonged or high dose corticosteroid use

• Liver cirrhosis

• Chronic pancreatitis

• Insulin-dependent diabetes mellitus

• Metastases, haematological malignancies or chemotherapy

• Patients on dialysis (CVVH or other)

• Pre-existent renal failure (on dialysis)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Organ Failure
• Sepsis
• Toxemia

Intervention

Dietary Supplement:
• L-citrulline supplementation
L-citrulline, 1.8micromol/kg/min, during 8 hours continuously supplemented
• L-alanine
L-alanine enteral infusion, isocaloric dosage (3.6 micromol/kg/min), during 8 hours, continuously supplemented

Locations

Country	Name	City	State
Netherlands	University Hospital Maastricht	Maastricht	Limburg

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

References & Publications (5)

Barr FE, Tirona RG, Taylor MB, Rice G, Arnold J, Cunningham G, Smith HA, Campbell A, Canter JA, Christian KG, Drinkwater DC, Scholl F, Kavanaugh-McHugh A, Summar ML. Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: potential therapy for postoperative pulmonary hypertension. J Thorac Cardiovasc Surg. 2007 Aug;134(2):319-26. — View Citation

Hallemeesch MM, Lamers WH, Deutz NE. Reduced arginine availability and nitric oxide production. Clin Nutr. 2002 Aug;21(4):273-9. Review. — View Citation

Lehr HA, Bittinger F, Kirkpatrick CJ. Microcirculatory dysfunction in sepsis: a pathogenetic basis for therapy? J Pathol. 2000 Feb;190(3):373-86. Review. — View Citation

Rougé C, Des Robert C, Robins A, Le Bacquer O, Volteau C, De La Cochetière MF, Darmaun D. Manipulation of citrulline availability in humans. Am J Physiol Gastrointest Liver Physiol. 2007 Nov;293(5):G1061-7. Epub 2007 Sep 27. — View Citation

Wu G, Morris SM Jr. Arginine metabolism: nitric oxide and beyond. Biochem J. 1998 Nov 15;336 ( Pt 1):1-17. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To study stimulating effects of prolonged (8h) enteral L-citrulline supplementation on the normalisation of the arginine-NO metabolism		8 hours	No
Secondary	Secondary study endpoints are the microcirculation, the vascular permeability and organ function scores.		within 8 hours	No