Directed Immuno Nutrition by L-arginine for Critically Ill Patients (Immunolarg)
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Randomized Directed Immuno Nutrition by L-arginine for Critically Ill Patients|
- Expression of HLA-DR in the L-arginine group as compared to the placebo group [ Time Frame: on day 3 ] [ Designated as safety issue: No ]
- HLA-DR on day 7, IL-10 and IL-17 on day 3 and 7, MDSC on day 3 and 7 [ Time Frame: on day 3 and on day 7 ] [ Designated as safety issue: No ]
- Nosocomial infections [ Time Frame: in the first 15 days ] [ Designated as safety issue: No ]
- Safety issue: organ failure score (SOFA score) on day 3 and 7; issue from ICU [ Time Frame: on day 3 and 7 ] [ Designated as safety issue: Yes ]
|Study Start Date:||November 2009|
|Study Completion Date:||January 2011|
|Primary Completion Date:||November 2010 (Final data collection date for primary outcome measure)|
Active Comparator: L-arginine
5-day L-arginine treatment (200 mg/kg)
5-day L-arginine treatment
Placebo Comparator: placebo
5-day placebo treatment
5-day placebo treatment
Background : A meta-analysis has demonstrated the beneficial effect of immuno nutrition in surgical patients, leading to half reduction of incidence of nosocomial infections (HEYLAND DK, JAMA ; 2001). This beneficial effect seems to be related to L-arginine content of formula. In medical intensive care, such an improvement has not been shown, in spite of similar impairment of immune response, which could be due to a more heterogenous population. Our hypothesis is that this beneficial effect could be observed in selected patients of medical intensive care units. L-arginine is a semi-essential amino acid that is the precursor of nitric oxide (NO) synthesis. NO is involved in immune response regulation and has antimicrobial properties, notably into airways where it can be measured in exhaled gas. A decrease in exhaled and nasal NO has been demonstrated in critically ill patients, which may suggest an impairment of its production.
Objectives : The aim of this study is to evaluate the immune effects of enteral L-arginine administration in non surgical critically ill patients. These patients will be selected based on the decrease in nasal NO: directed immuno nutrition. The main objective is to demonstrate that L-arginine administration, as compared to placebo administration, increases nasal NO and enhances immune functions (increase in HLA-DR expression on monocytes, modification of circulating Myeloid-Derived Suppressor Cells (MDSC), decrease in IL-6, IL-17 plasmatic concentrations): stimulation of immune response. The secondary objective is to demonstrate the safety of L-arginine administration on organ failure and on the incidence of nosocomial infections.
This is a monocentric therapeutic trial, randomized and double blind: standard enteral nutrition plus L-arginine (200 mg/kg/d for 5 days from the admission in ICU) versus standard enteral nutrition plus placebo.
Methods-Patients: Non surgical patients admitted in a single medical intensive care unit, under mechanical ventilation for an expected duration > 2 days, with decreased concentrations of nasal NO (< 60 ppb), without severe sepsis or septic shock, will be enrolled. On admission (before treatment), the severity will be evaluated (SAPS II and SOFA score) together with an assessment of plasmatic L-arginine, cytokines (IL-6, IL-17), MDSC, and expression of HLA-DR by monocytes. The same evaluation will be repeated on day 4 (during treatment) and on day 7 (after treatment). The enrolment of 50 patients is statistically enough to demonstrate an increased expression of HLA-DR in the L-arginine group as compared to the placebo group on day 4.
Expected results and perspectives: The aim of this study is to demonstrate the validity of the concept of directed immune stimulation by the sole L-arginine in medical intensive care unit, the patients being selected based on their decrease in exhaled and nasal NO concentrations. This pathophysiological study is the necessary first step before conducting a large clinical trial aimed at demonstrating a reduction of nosocomial infection incidence by L-arginine.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01038622
|Medical Intensive Care Unit, Pompidou Hospital|
|Paris, France, 75015|
|Principal Investigator:||Jean Marc TADIE, MD||Assistance Publique - Hôpitaux de Paris|