L-citrulline Supplementation During Sepsis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Sepsis, Multiple Organ Failure

Intervention / Treatment
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* Dietary Supplement: L-citrulline supplementation
* Dietary Supplement: L-alanine


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To study stimulating effects of prolonged (8h) enteral L-citrulline supplementation on the normalisation of the arginine-NO metabolism |  | 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary study endpoints are the microcirculation, the vascular permeability and organ function scores. |  | within 8 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sepsis, microcirculation, nitric oxide, citrulline