L-Citrulline Supplementation During Sepsis - Full Text View

Sponsors and Collaborators:	Maastricht University Medical Center ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by:	Maastricht University Medical Center
ClinicalTrials.gov Identifier:	NCT00628381

Purpose

The purpose of this study is to study the stimulating effects of prolonged (72h) intravenous L-citrulline supplementation on the microcirculation, on the Arginine-NO metabolism, systemic hemodynamics, vascular permeability, and organ function and disease severity scores.

Condition	Intervention	Phase
Sepsis Multiple Organ Failure	Drug: L-citrulline infusion Drug: L-alanine	Phase II

MedlinePlus related topics: Sepsis

Drug Information available for: Nitric oxide Arginine Arginine hydrochloride Citrulline Alanine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Arginine and Nitric Oxide (NO) Metabolism in Sepsis; Effects of 72h L-Citrulline Supplementation on Whole Body and Splanchnic Microcirculation in Severely Septic Patients

Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:

To study stimulating effects of prolonged (72h) intravenous L-citrulline supplementation on the microcirculation, by gastric tonometry, sublingual orthogonal polarization spectral imaging (OPS), skin vascular blood flow by Laser-Doppler fluxmetry [ Time Frame: 72 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Secondary study endpoints are the arginine-NO metabolism using stable isotope infusion, vascular permeability assessed by the skin fluorescence of intravenously injected fluorescein, and organ function scores. [ Time Frame: within 72 hours ] [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	March 2009
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
AA: Experimental 16 ICU patients with severe sepsis will get a L-citrulline 72 h intravenous supplementation. 8 patients will be conducted in a PILOT phase to examine the dose-response of L-citrulline. The other 8 patients will be enrolled later in this study, together with the patients in the placebo group.	Drug: L-citrulline infusion L-citrulline, dosage will be determined in a PILOT study, during 72 hours continuously infused.
AB: Active Comparator 8 ICU patients with severe sepsis will get a placebo infusion (L-alanine) during 72 hours	Drug: L-alanine L-alanine intravenous infusion, isocaloric doses (determined in PILOT phase of this study), during 72 hours, continuously infused

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00628381

Contacts

Contact: Nina Wijnands, MD, PhD-student	+31-43-3884502	n.wijnands@ah.unimaas.nl
Contact: Martijn Poeze, MD, PhD	+31-43-3874425	m.poeze@ah.unimaas.nl

Locations

Netherlands, Limburg
University Hospital Maastricht
Maastricht, Limburg, Netherlands, 6202 AZ

Sponsors and Collaborators

Maastricht University Medical Center

ZonMw: The Netherlands Organisation for Health Research and Development

Investigators

Principal Investigator:

Martijn Poeze, MD, PhD

Department of surgery

More Information

Publications:

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.

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.

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

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

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

Responsible Party:	Department of surgery, University hospital Maastricht ( M.Poeze, MD, PhD, )
Study ID Numbers:	MEC-08, ZON/NW 40-00806-98-114
Study First Received:	February 26, 2008
Last Updated:	January 14, 2009
ClinicalTrials.gov Identifier:	NCT00628381
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht University Medical Center:

sepsis
microcirculation
nitric oxide
citrulline

Study placed in the following topic categories:

Nitric Oxide
Systemic Inflammatory Response Syndrome
Sepsis

Shock
Multiple Organ Failure
Inflammation

Additional relevant MeSH terms:

Pathologic Processes
Infection

ClinicalTrials.gov processed this record on January 16, 2009