Immuno Nutrition by L-citrulline for Critically Ill Patients

Study Overview
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Brief Summary
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The main objective of this study is to demonstrate that the only administration of L-citrulline, can improve immune functions in critically ill patients at high risk of nosocomial infection.

Detailed Description
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This is a multicentric therapeutic trial, randomized and double blind: standard enteral nutrition plus L-citrulline (5 grams/12 Hours for 5 days from the admission in Intensive Care Unit (ICU)) versus standard enteral nutrition plus placebo. Methods-Patients: Non-surgical patients admitted in medical intensive care unit, under mechanical ventilation for an expected duration > 2 days, without severe sepsis or septic shock, will be enrolled. Symptoms leading for ICU admission ongoing for five days maximum. On admission (before treatment), the severity will be evaluated with the Sepsis-related Organ Failure Assessment (SOFA) score together with an assessment of plasmatic arginine, cytokines (InterLeukin-6 (IL6) ), and expression of Human Leukocyte Antigen - antigen D Related (HLA-DR) by monocytes. The same evaluation will be repeated on day 3 (during treatment) and on day 7 (after treatment). The enrolment of 100 patients is statistically enough to demonstrate a decreased SOFA scores in the L-citrulline group as compared to the placebo group on day 7.

Official Title
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Immuno Nutrition by L-citrulline for Critically Ill Patients

Conditions
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Intubation, Pulmonary Ventilation

Intervention / Treatment
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* Procedure: Enteral nutrition
* Dietary Supplement: L-Citrulline
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age > 18 years medical patient (absence of recent surgery or trauma) initial aggression < 5 days mechanically ventilated with expected duration of mechanical ventilation > 2 days exclusive enteral nutrition absence of previous immunosuppression Exclusion Criteria: severe sepsis septic shock obesity defined as BMI above 40 pregnancy

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-Citrulline group<br>Enteral nutrition 5-day L-citrulline treatment (10 grams/day) | Procedure: Enteral nutrition<br> <br> Dietary Supplement: L-Citrulline<br> <br> |
| Placebo Comparator: Control group<br>Enteral nutrition 5-day placebo treatment | Procedure: Enteral nutrition<br> <br> Dietary Supplement: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Organ failure score comparison D7 | Organ failure score (SOFA score) on day 7 in the L-citrulline group as compared to the placebo group | At day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Organ failure score comparison D3 | Organ failure score (SOFA score) on day 3 in the L-citrulline group as compared to the placebo group | At day 3 | 
| SOFA score evolution between randomisation and D7 | Binary criterion of success or failure : - Success is defined by: an improved SOFA score of at least 2 points from randomization to Day 7 or an improvement in the general condition yielding the release of the unit; - Failure is defined by an improved SOFA score but less than 2 points, no improvement or worsening of the SOFA score from randomization to Day 7 or the patient's death before J7; | up to 7 days | 
| Expression of HLA-DR | Expression of HLA-DR in the L-citrulline group as compared to the placebo group | At day 7 | 
| Plasmatic concentration of IL6 | Comparison of the plasmatic concentration of interleukin-6 between the L-citrulline group and the placebo group | At day 7 | 
| HLA-DR | Comparison of the percentage of expression of monocytic HLA-DR between the L-citrulline group and the placebo group | At day 7 | 
| Plasmatic concentration of L-arginine | Comparison of the plasmatic concentration of L-arginine and its metabolites between the L-citrulline group and the placebo group | At day 7 | 
| Incidence of nosocomial infections | Comparison between the L-citrulline group and the placebo group | during the stay in the ICU, an average of 7 days | 
| Length of stay | Length of stay in ICU and hospital: Comparison between the L-citrulline group and the placebo group | during the stay in hospital, up to 28 days | 
| Mortality | Mortality in intensive care and in hospital : Comparison between the L-citrulline group and the placebo group Duration of mechanical ventilation. | during the stay in hospital, up to 28 days | 
| Duration of mechanical ventilation | Duration of mechanical ventilation: Comparison between the L-citrulline group and the placebo group | during the stay in ICU, an average of 7 days |