Citrulline and Arginase Activity in Severe Sepsis and Septic Shock

NCT03837730 | Completed

• 1 other identifier: P/2018/353
• Study Type: observational
• Target: 118
• Locations: 1 country
• Sites: 1

Brief Summary

Sepsis is an acute pathology defined as an inappropriate response of the host to infection, resulting in the onset of organ failure (Quick SOFA ≥2, or SOFA ≥2). Septic shock is a sepsis associated with an elevation of lactate ≥ 2 mmol / l and an arterial hypotension requiring vasoactive drugs. Several studies highlighted that sepsis is associated with a plasma L-arginine deficiency. This deficiency induces a lower availability of L-arginine for multiple metabolic pathways including those involved in the synthesis of nitric oxide (NO) in the vascular endothelium via NO synthase. NO is the main endogenous vasodilator mediator, a lower synthesis induces a vascular and endothelial dysfunction that can promote the occurrence of an organic dysfunction during sepsis. Decrease in available NO was confirmed in patients with sepsis and appears correlated with severity. L-arginine deficiency can have multiple origins:

• L-arginine deficiency resulting from a decrease in endogenous production from citrulline synthesized by the enterocytes. Such enterocyte dysfunction has been confirmed in patients with sepsis and is characterized biologically by elevated plasma levels of I-FABP (intestinal fatty acid binding protein - enterocyte-specific protein, cytolysis marker) and lower than that of citrulline (hypocitrullinemia, marker of lower activity).
• L-arginine deficiency may also result from a catabolism increase via arginase activity increased. This ubiquitous enzyme, having 2 isoforms (Arg1 and Arg2), allows the synthesis of urea and ornithine from L-arginine. An increase in arginase activity would decrease the available reserves of L-arginine for NO synthesis. The objectives of this work is to evaluate, in patients with severe sepsis or septic shock, the prognostic value of the plasma arginase activity and the plasma expression of 2 isoforms Arg1 and Arg2, their kinetics, and the link between activity / expression of arginase and enterocyte dysfunction.

Conditions

Intensive Care Units; Infection; Biomarkers; Sepsis; Septic Shock

Keywords

ICU, sepsis, septic shok, arginase, citrulline

Outcome Measures

Primary Outcomes (1)

• prognostic value of plasma arginase activity and expression at ICU admission in patients with severe sepsis or septic shock

  activity / expression of plasma arginase at ICU admission and 28-day mortality rate from admission to intensive care

  28 days

Secondary Outcomes (2)

• activity / expression kinetic of plasma arginase

  during the first 7 days of ICU admission

• prognostic value of enterocyte damage

  28 days

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

patients admitted to the ICU for severe sepsis or septic shock

You may qualify if:

• years old or older
• Patient admitted to ICU
• Diagnosis, suspected or confirmed, of severe sepsis or septic shock
• Expected ICU stay of at least 2 days
• Affiliation to a social security system or recipient of a such system
• Signed informed consent

You may not qualify if:

• Pregnancy
• Chronic intestinal pathology
• Chronic renal failure defined by creatinine clearance \<50 ml / min / 1.73m2 (CKD-EPI)
• Severe hepatic insufficiency (Child-Pugh stage C score)
• Legal incapacity or limited legal capacity
• Subject unlikely to cooperate with the study and / or weak cooperation anticipated by the investigator

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Besancon: lead

Study Sites (1)

CHU de BESANCON

Besançon, 25030, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood sample at ICU admission, day 3 and day 7 biomarkers analysis: arginase activity, citrulline and IFABP

MeSH Terms

Conditions

Infections; Sepsis; Shock, Septic

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Gaël PITON, MD

  CHU DE BESANCON

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2019
• First Posted: February 12, 2019
• Study Start: May 28, 2019
• Primary Completion: September 30, 2022
• Study Completion: October 30, 2022
• Last Updated: January 17, 2025

Record last verified: 2025-01

Locations

FR (1)