Directed Immuno Nutrition by L-arginine for Critically Ill Patients (Immunolarg)
Recruitment status was Recruiting
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First Received Date ICMJE | December 22, 2009 | ||||||||
Last Updated Date | December 23, 2009 | ||||||||
Start Date ICMJE | November 2009 | ||||||||
Estimated Primary Completion Date | November 2010 (final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
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 ] | ||||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | Complete list of historical versions of study NCT01038622 on ClinicalTrials.gov Archive Site | ||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Outcome Measures ICMJE | |||||||||
Original Other Outcome Measures ICMJE | |||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Directed Immuno Nutrition by L-arginine for Critically Ill Patients | ||||||||
Official Title ICMJE | Randomized Directed Immuno Nutrition by L-arginine for Critically Ill Patients | ||||||||
Brief Summary | 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. |
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Detailed Description | 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. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase | Phase 4 | ||||||||
Study Design ICMJE | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
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Condition ICMJE | Critically Ill | ||||||||
Intervention ICMJE |
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Study Arm (s) |
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Publications * | Marik PE, Zaloga GP. Immunonutrition in critically ill patients: a systematic review and analysis of the literature. Intensive Care Med. 2008 Nov;34(11):1980-90. Epub 2008 Jul 15. Review. | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE | 50 | ||||||||
Estimated Completion Date | January 2011 | ||||||||
Estimated Primary Completion Date | November 2010 (final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE | Inclusion criteria :
Exclusion criteria :
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Gender | Both | ||||||||
Ages | 18 Years and older | ||||||||
Accepts Healthy Volunteers | No | ||||||||
Contacts ICMJE |
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Location Countries ICMJE | France | ||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT01038622 | ||||||||
Other Study ID Numbers ICMJE | P090203 | ||||||||
Has Data Monitoring Committee | No | ||||||||
Responsible Party | Yannick Vacher, Department Clinical Research of developpement | ||||||||
Study Sponsor ICMJE | Assistance Publique - Hôpitaux de Paris | ||||||||
Collaborators ICMJE | |||||||||
Investigators ICMJE |
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Information Provided By | Assistance Publique - Hôpitaux de Paris | ||||||||
Verification Date | December 2009 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |