Measurement of Intestinal Permeability in Intensive Care Patients With Single or Multiple Organ Failure (BLUE-REA)

Multivisceral failure syndrome (MVFS) in humans is associated with a very high risk of mortality, ranging between 30 and 50%. This syndrome is associated with significant systemic inflammation and a high risk of bacteremia, the origin of which is not always identified. Among the possible causes of bacteremia, digestive translocation is the most probable but has not been formally proven to date. This translocation is made possible by the numerous cellular and metabolic alterations secondary to MVFS, which can lead to increased intestinal barrier permeability. Intestinal permeability is currently not systematically evaluated in clinical practice in humans.

This increased intestinal permeability, associated with the presence of inflammatory markers and a septic state, has been studied in several animal models ranging from the fruit fly (Drosophila) to the mouse. These studies have shown a high risk of mortality associated with increased intestinal permeability.

We propose to use this methodology in intensive care patients with at least one organ failure to investigate the link between increased intestinal permeability and survival chances.

Study Overview

• Status: Recruiting
• Conditions: Infection in ICU; Multivisceral Failure Syndrome; Monovisceral Failure
• Intervention / Treatment: Dietary supplement: enteric dyed solution

• Study Type: Observational
• Enrollment (Estimated): 126

Contacts and Locations

• Study Contact: Name: Michael RERA, PhD; Phone Number: +33781945974; Email: michael.rera@cnrs.fr
• Study Contact Backup: Name: Rachel HAUS, PhD; Email: evdg-dpar.contact.fct@intradef.gouv.fr

Study Locations

• France
  • Vincennes, France
    • Recruiting
    • Hopital Bégin
    • Contact: Clément Dubost, MD, PhD; Phone Number: +331 43 98 50 48; Email: clement.dubost@ens-paris-saclay.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

hosptalized adults in ICU, France.

Description

Inclusion Criteria:

Patient with single organ failure, secondary to sepsis, hospitalized in intensive care for a foreseeable duration of > 48 hours

• SAPS2 between 20 and 40 at the sixth hour after the diagnosis of organ failure.
• Consent from the patient or their trusted person.
• Affiliation to a social security system.
• Functional digestive tract and possible feeding (per os or via a nasogastric tube whose indication was determined independently of the study's needs).

Second group of patients with multi-organ failure:

• Multi-organ failure syndrome with at least 2 organ failures, secondary to sepsis.
• SAPS2 between 60 and 80 at the sixth hour after the diagnosis of organ failure.
• Consent from the patient or their trusted person.
• Affiliation to a social security system.
• Functional digestive tract and possible feeding (conscious patient able to swallow or with a nasogastric tube whose indication was determined independently of the study's needs).

Exclusion Criteria:

• Pregnant and breastfeeding women;
• Minors;
• Persons under administrative and judicial supervision;
• Absence of a functional digestive tract (patient unable to swallow and absence of a nasogastric tube, contraindication to enteral feeding);
• Patients with gastroparesis;
• Refusal of the patient or their trusted person;
• Patient with a SAPS2 at the sixth hour after the diagnosis of organ failure < 20 or between 40 and 60 or > 80.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
patients with mono-organ failure; 20 < SAPS2 < 40	Dietary supplement: enteric dyed solution; Oral administration of 0.5 mg/kg of body weight of food coloring dye
patients with multi-visceral failure; 60 < SAPS2 < 80	Dietary supplement: enteric dyed solution; Oral administration of 0.5 mg/kg of body weight of food coloring dye

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intestinal failure and survival 90 days post inclusion	Evaluation of the impact of changes in permeability (classified into 3 categories: absent, moderately increased, and highly increased) on patient survival at day 90	2024-2027

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intestinal permeability as a function of organ failure	Comparison of average intestinal permeability between patients with a single organ failure versus multiple organ failures on day 1 in the blood (plasma)	2024-2027

Collaborators and Investigators

• Sponsor: Direction Centrale du Service de Santé des Armées
• Collaborators: Centre Borelli UMR 9010
• Investigators: Principal Investigator: Clément DUBOST, MD, PhD, National teaching army hospital BEGIN (Hôpital National d'Instruction des Armées BEGIN)

Publications and helpful links

General Publications

• Angarita SAK, Duarte S, Russell TA, Ruchala P, Elliott IA, Whitelegge JP, Zarrinpar A. Quantitative Measure of Intestinal Permeability Using Blue Food Coloring. J Surg Res. 2019 Jan;233:20-25. doi: 10.1016/j.jss.2018.07.005. Epub 2018 Jul 27.
• Dambroise E, Monnier L, Ruisheng L, Aguilaniu H, Joly JS, Tricoire H, Rera M. Two phases of aging separated by the Smurf transition as a public path to death. Sci Rep. 2016 Mar 22;6:23523. doi: 10.1038/srep23523.
• Doig CJ, Sutherland LR, Sandham JD, Fick GH, Verhoef M, Meddings JB. Increased intestinal permeability is associated with the development of multiple organ dysfunction syndrome in critically ill ICU patients. Am J Respir Crit Care Med. 1998 Aug;158(2):444-51. doi: 10.1164/ajrccm.158.2.9710092.
• Gayat E, Cariou A, Deye N, Vieillard-Baron A, Jaber S, Damoisel C, Lu Q, Monnet X, Rennuit I, Azoulay E, Leone M, Oueslati H, Guidet B, Friedman D, Tesniere A, Sonneville R, Montravers P, Pili-Floury S, Lefrant JY, Duranteau J, Laterre PF, Brechot N, Chevreul K, Michel M, Cholley B, Legrand M, Launay JM, Vicaut E, Singer M, Resche-Rigon M, Mebazaa A. Determinants of long-term outcome in ICU survivors: results from the FROG-ICU study. Crit Care. 2018 Jan 18;22(1):8. doi: 10.1186/s13054-017-1922-8.
• Harris CE, Griffiths RD, Freestone N, Billington D, Atherton ST, Macmillan RR. Intestinal permeability in the critically ill. Intensive Care Med. 1992;18(1):38-41. doi: 10.1007/BF01706424.

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2025
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: February 11, 2025
• First Submitted That Met QC Criteria: February 20, 2025
• First Posted (Actual): February 25, 2025

Study Record Updates

• Last Update Posted (Actual): August 31, 2026
• Last Update Submitted That Met QC Criteria: August 27, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Shock; Multiple Organ Failure
• Other Study ID Numbers: 2021PPRC02; 2023-A02005-40 (Other Identifier: Comité de protection des personnes Ouest IV)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No