L-citrulline Supplementation During Sepsis

Sponsor

Maastricht University Medical Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT00628381

Collaborator

ZonMw: The Netherlands Organisation for Health Research and Development (Other)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Sepsis Multiple Organ Failure	Dietary Supplement: L-citrulline supplementation Dietary Supplement: L-alanine	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2011

Anticipated Primary Completion Date :

Jan 1, 2013

Anticipated Study Completion Date :

Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AA 24 ICU patients with severe sepsis will get a L-citrulline 8 h enteral supplementation.	Dietary Supplement: L-citrulline supplementation L-citrulline, 1.8micromol/kg/min, during 8 hours continuously supplemented
Active Comparator: AB 24 ICU patients with severe sepsis will get an alternative isocaloric amino acid supplementation (L-alanine) during 8 hours	Dietary Supplement: L-alanine L-alanine enteral infusion, isocaloric dosage (3.6 micromol/kg/min), during 8 hours, continuously supplemented

Arm

Intervention/Treatment

Experimental: AA

24 ICU patients with severe sepsis will get a L-citrulline 8 h enteral supplementation.

Dietary Supplement: L-citrulline supplementation

L-citrulline, 1.8micromol/kg/min, during 8 hours continuously supplemented

Active Comparator: AB

24 ICU patients with severe sepsis will get an alternative isocaloric amino acid supplementation (L-alanine) during 8 hours

Dietary Supplement: L-alanine

L-alanine enteral infusion, isocaloric dosage (3.6 micromol/kg/min), during 8 hours, continuously supplemented

Outcome Measures

Primary Outcome Measures

To study stimulating effects of prolonged (8h) enteral L-citrulline supplementation on the normalisation of the arginine-NO metabolism [8 hours]

Secondary Outcome Measures

Secondary study endpoints are the microcirculation, the vascular permeability and organ function scores. [within 8 hours]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)