Track topics on Twitter Track topics that are important to you
The main objective of this proof-of-concept study is to demonstrate that the only administration of L-arginine, based on a suspected deficit monitored by nasal nitric oxide measurement, can improve immune functions in critically ill patients at high risk of nosocomial infection.
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.
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Medical Intensive Care Unit, Pompidou Hospital
Assistance Publique - Hôpitaux de Paris
Published on BioPortfolio: 2014-08-27T03:17:05-0400
This study evaluates the addition of L-Arginine to the usual regimen in the treatment of schizophrenia in adults. As a requisite of crossover design, half of the participants started with...
The goal of this clinical research study is to learn if L-arginine can help control side effects of anti-cancer drugs such as high blood pressure, protein in the urine, and kidney problems...
The objective of this trial is to determine the safety and effect on pulmonary function of 14 days of inhaled L-arginine versus placebo administered over a period of 14 days in a cohort of...
The purpose of this study is to determine whether adjunctive L-arginine and vitamin D can improve response to standard short course TB therapy in people with newly diagnosed pulmonary TB.
This is a study of ADI-PEG 20 (pegylated arginine deiminase), an arginine degrading enzyme versus placebo in patients with malignant pleural mesothelioma with low argininosuccinate synthet...
Camicinal is a novel, nonmacrolide, motilin receptor agonist that accelerates gastric emptying in critically ill patients with established feed intolerance. The primary question was whether the preemp...
Corynebacterium glutamicum SNK 118 was metabolically engineered with improved L-arginine titer. Considering the crucial role of NADPH level in L-arginine production, pntAB (membrane-bound transhydroge...
Placebo beverage conditions remain a key element in the methodological toolkit for alcohol researchers interested in evaluating pharmacological and nonpharmacological factors influencing the effects o...
Methods are described for determination of arginine-specific mono-ADP-ribosyltransferase activity of purified proteins and intact cells by monitoring the transfer of ADP-ribose from NAD to a model sub...
Different to spirituality, the placebo-effect is well operationalized. Against this background, an attempt is made to look at a possible phenomenological relationship between the therapeutic effective...
An enzyme that activates arginine with its specific transfer RNA. EC 188.8.131.52.
A family of ENZYMES that, in the presence of calcium ion, converts ARGININE to CITRULLINE in proteins.
An enzyme that catalyzes the phosphorylation of the guanidine nitrogen of arginine in the presence of ATP and a divalent cation with formation of phosphorylarginine and ADP. EC 184.108.40.206.
Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.
Enzymes that catalyze the methylation of arginine residues of proteins to yield N-mono- and N,N-dimethylarginine. This enzyme is found in many organs, primarily brain and spleen.
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...
Alternative Medicine Cleft Palate Complementary & Alternative Medicine Congenital Diseases Dentistry Ear Nose & Throat Food Safety Geriatrics Healthcare Hearing Medical Devices MRSA Muscular Dyst...
Surgery is a technology consisting of a physical intervention on tissues. All forms of surgery are considered invasive procedures; so-called "noninvasive surgery" usually refers to an excision that does not penetrate the structure being exci...