Impact of Vascular Calcification and CASR Expression by Monocytes in Septic Shock (CASRCHOC)

In septic shock, bacterial LPS is able to activate the CaSR of cardiomyocytes inducing their apoptosis in vitro. CaSR activation in monocytes is responsible for activation of the NLRP3 inflammasome and macropinocytosis. In front of this immune axis, a variation in the monocyte expression of the CaSR is expected in the state of shock. This is already observed in other pathologies such as renal failure or in animal models of severe burns. If this is considered as an overall reflection of CaSR expression in the body, it would be consistent with the phosphocalcic disturbances associated with septic shock. The phosphocalcic balance is often modified, and not treated during the acute episode, with in particular hypocalcaemia which could be consecutive to a hyperactivation or overexpression of the CaSR. This study proposes to explore for the first time the expression of monocytic CaSR in patients in a state of shock, with possible therapeutic perspectives by the existence of calcimimetics and calcilytics. In this study, the investigators propose to explore the CasR and its implication in septic shock in a three - part protocol : measurement by flow cytometry of monocyte expression of CASR (primary objective) and CD33, CD14, CD163, CD16 and HLA-DR), survey of clinical and biological parameters in patients with septic shock and healthy volunteers and acquisition of calcium score in patients with septic shock.

Study Overview

• Status: Recruiting
• Conditions: Inflammation; Septic Shock; Calcium Sensing Receptor; Calcium Phosphate Disorders; Monocyte
• Intervention / Treatment: Biological: blood sampling

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Quintana SOULIER; Phone Number: 33+322057870; Email: Soulier-Zaninka.Quintana@chu-amiens.fr

Study Locations

• France
  • Amiens, France, 80480
    • Recruiting
    • CHRU Amiens
    • Contact: Julien Maizel
    • Contact: Quintana SOULIER; Phone Number: 33+322057870; Email: Soulier-Zaninka.Quintana@chu-amiens.fr
    • Contact: Aurélien MARY
    • Contact: Romuald Mentaverri
    • Contact: Hervé Dupont, Pr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female patients over the age of 18,
• patients who have not participated in a study evaluating an investigational drug in the 30 days preceding the samples,
• intensive care patients in a state of septic shock within the first 24 hours of the introduction of pressor amines,
• French resident year-round,
• lactate > 2mmol/L,
• patients with social security coverage.

Exclusion Criteria:

• Patients in hemorrhagic shock,
• history of parathyroidectomy, patient with hypersecretion of PTHrp,
• sarcoidosis,
• genetic disturbance of CaSR including familial hypocalciuric hypercalcaemia,
• current immunosuppressant treatment (anticalcineurin, mTOR inhibitor, methotrexate, high-dose corticosteroids excluding hydrocortisone and fludrocortisone),
• chronic myelomonocytic leukemia,
• patients with febrile neutropenia,
• patients with acquired or constitutional immune system,
• pregnant or breastfeeding patient,
• patients under curators, guardianship or safeguard of justice.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: healthy volunteers
Experimental: patients in septic shock	Biological: blood sampling; Patients with septic shock will have three differents times of blood sampling and of clinical and biological statements. Healthy volunteers will have a unique visit to collect clinical data and blood samples.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monocyte CaSR expression in healthy patient	Monocyte CaSR expression in healthy patient	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monocyte CasR expression in patient with septic shock	Monocyte CasR expression in patient with septic shock	day 0
Monocyte CasR expression in patient with septic shock	Monocyte CasR expression in patient with septic shock	day 2
Monocyte CasR expression in patient with septic shock	Monocyte CasR expression in patient with septic shock	day 7

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire, Amiens

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2025
• Primary Completion (Actual): April 1, 2025
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: February 25, 2025
• First Submitted That Met QC Criteria: February 25, 2025
• First Posted (Actual): February 28, 2025

Study Record Updates

• Last Update Posted (Actual): April 25, 2025
• Last Update Submitted That Met QC Criteria: April 24, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Inflammation; Septic shock; Monocyte; Calcium Sensing Receptor; Calcium Phosphate disorders
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Calcium Metabolism Disorders; Calcinosis; Inflammation; Shock; Shock, Septic; Vascular Calcification
• Other Study ID Numbers: PI2023_843_0034

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