Directed Immuno Nutrition by L-arginine for Critically Ill Patients (Immunolarg)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01038622
First received: December 22, 2009
Last updated: September 17, 2013
Last verified: December 2009
  Purpose

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.


Condition Intervention Phase
Critically Ill
Drug: L-arginine
Drug: placebo
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 30
Study Start Date: November 2009
Study Completion Date: January 2011
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: L-arginine
5-day L-arginine treatment (200 mg/kg)
Drug: L-arginine
5-day L-arginine treatment
Placebo Comparator: placebo
5-day placebo treatment
Drug: placebo
5-day placebo treatment

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  • enteral nutrition
  • absence of previous immunosuppression
  • nasal NO on day 1 of ICU stay < 60 ppb

Exclusion criteria :

  • severe sepsis
  • septic shock
  • condition associated with a decreased nasal NO concentration (cystic fibrosis, nasal polyposis, primary ciliary dyskinesia
  • pregnancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01038622

Locations
France
Medical Intensive Care Unit, Pompidou Hospital
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Jean Marc TADIE, MD Assistance Publique - Hôpitaux de Paris
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01038622     History of Changes
Other Study ID Numbers: P090203
Study First Received: December 22, 2009
Last Updated: September 17, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
L-arginine
Nasal NO
Nosocomial infection
Immune function
HLA-DR expression
Critically ill
Medical ICU patients

Additional relevant MeSH terms:
Critical Illness
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on April 17, 2014