Citrullinemia for the Prediction of Enteral Nutrition Tolerance Among Critically Ill Patients (PREDICT)

The French intensive care societies (SRLF and SFAR), in agreement with the European and American societies for enteral and parenteral nutrition, recommend to quickly administer an artificial nutrition to patients admitted to ICU and for which it is expected that they will not be able to eat normally in the three days of admission.

Enteral nutrition should be used in priority if the gut is functioning. However, intolerance to enteral nutrition, such as vomiting, regurgitation, increased residual gastric volume, or diarrhea, occurs in 40% of patients hospitalized in ICU receiving enteral nutrition. Intolerance to enteral nutrition leads to the risk of not receiving enough nutrition. Feeding intolerance also exposes to the risk of acute mesenteric ischemia, especially in the most severe patients under catecholamine for shock. Currently, it is not possible to predict intolerance to enteral nutrition in ICU patients. Thus, the diagnosis of intolerance is made a posteriori while enteral nutrition is in progress.

Citrullinemia (normal concentration of 20 to 60 μmol / L), could be a good biomarker of the function of enterocytes involved in the absorption of food.

The aim of this study is to evaluate the interest of citrullinemia to predict tolerance to enteral nutrition in ICU patients.

Study Overview

• Status: Unknown
• Conditions: Biomarkers; Enteral Nutrition; Intensive Care Unit
• Intervention / Treatment: Drug: N2-L-Alanyl-L-Glutamine (Substance)

Detailed Description

Citrulline is an amino acid mainly produced by enterocytes from glutamine.

Citrullinemia ≤ 20μmol/L is a biomarker of enterocyte mass reduction, secondary to the reduction of small bowel length or secondary to villous atrophy diseases. A patient with low citrullinemia is probably at risk of enteral nutrition malabsorption.

Citrulline generation test consists of measuring the course of citrullinemia after an oral or intravenous administration of glutamine, the main precursor of citrulline. When the small bowel is functional, administration of glutamine is followed by the elevation of citrullinemia. On the contrary, when there is enterocyte dysfunction or reduction, citrullinemia does not vary after glutamine administration. Peeters et al have shown the feasibility of carrying out the citrulline generation test in patients hospitalized in the ICU. In this context, intravenous administration of glutamine (20 gr of 10% N2-L-Alanyl-L-Glutamine, dilution in 200 ml of water for injection, IV infusion over 30 minutes) followed by monitoring of citrullinemia (basal time and then after 90 minutes, on arterial sampling) is feasible and reproducible.

There is currently no data available on the relationship between citrullinemia measured at ICU admission and tolerance to enteral nutrition in the days following ICU admission. Similarly, the value of the citrulline generation test for evaluating enteral nutrition tolerance is unknown.

The investigators hypothesize that patients with low citrullinemia at ICU admission, as well as those with a decreased citrullinemia elevation after Dipeptiven bolus, will have less tolerance to enteral nutrition than patients with normal citrullinemia.

PREDICT is the first study evaluating the interest of citrullinemia and the citrulline generation test to predict feeding tolerance among critically ill patients.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gaël PITON, MD; Phone Number: +33 381668127; Email: gpiton@chu-besancon.fr
• Study Contact Backup: Name: Lucie VETTORETTI, PhD; Phone Number: +33381218378; Email: lvettoretti@chu-besancon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years old or older
• patient admited to ICU
• expected hospital stay of at least 3 days
• indication of enteral nutrition.
• presence of an arterial catheter
• signed informed consent

Exclusion Criteria:

• contraindication to enteral nutrition (e.g. non-functional digestive tract, mesenteric ischemia, occlusion, digestive fistula, active gastrointestinal bleeding)
• pregnancy ;
• chronic renal failure;
• chronic intestinal pathology

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: All patients; Citrulline genration test before starting enteral nutrition At ICU admission, a blood sample is collected (i) before and (ii) 90 minutes after N2-L-Alanyl-L-Glutamine administration	Drug: N2-L-Alanyl-L-Glutamine (Substance); 20 gr of 10% N2-L-Alanyl-L-Glutamine, dilution in 200 ml of water for injection, intravenous perfusion over 30 minutes; Other Names: Dipeptiven

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feeding intolerance at day-3 and citrulline generation test	Feeding intolerance evaluated at day-3 of enteral nutrition Citrulline generation test: variation of citrullinemia/90 minutes	Day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feeding intolerance at dat 3 and basal plasma citrulline	Feeding intolerance at day-3 of enteral nutrition Citrullinemia measured the first day just before initiation of enteral nutrition	Day 3
Citrullinemia and cumulative amount of enteral nutrition	Link between citrullinemia and cumulative amount of enteral nutrition administred during the first three days of ICU stay	Day 3
Citrullinemia and enteral nutrition complications occurrence	Link between citrullinemia levels and occurrence of acute mesenteric ischemia and inhalation pneumopathy during the first week of enteral nutrition	First week

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon
• Investigators: Principal Investigator: Gaël PITON, MD, CHU de Besancon

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 15, 2019
• Primary Completion (ANTICIPATED): June 15, 2020
• Study Completion (ANTICIPATED): November 15, 2020

Study Registration Dates

• First Submitted: May 27, 2019
• First Submitted That Met QC Criteria: May 29, 2019
• First Posted (ACTUAL): May 30, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 4, 2019
• Last Update Submitted That Met QC Criteria: June 3, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: ICU; prediction; tolerance; enteral nutrition
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Urea Cycle Disorders, Inborn; Citrullinemia
• Other Study ID Numbers: API/2018/93

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No