Role of Type 2 Diabetes in Potentiating the Inflammatory Response Post Extracorporeal Circulation After Cardiac Surgery

NCT04432337 | Withdrawn DMC

• 1 other identifier: 19_RIPH2-15
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Adult cardiac surgery ensures the surgical treatment of valvular and coronary pathologies and of heart failure with the placement of ventricular assistance. Extracorporeal circulation (ECC) is one of the major technical advances associated with cardiac surgery to replace cardiac and pulmonary functions during surgery. ECC can nevertheless lead to postoperative complications, the origin of which is linked to the patient's initial contact with the circuit and membranes of the ECC. This contact triggers a series of humoral and cellular reactions that occur in the first few hours after the ECC and the inflammatory syndrome post ECC fades on its own and usually disappears between the 4th and 6th postoperative day. If the inflammatory response post ECC is most often transient, certain conditions will maintain and intensify this response at the origin of postoperative complications, possibly leading to the patient's death. Among these situations, the investigators find the notion of emergency cardiac surgery, a patient's age over 75 years and a preoperative history of decompensated heart failure, renal failure or type 2 diabetes (T2D). The inflammasome family of receptors of the nucleotide oligomerization domain (NOD) type, pyrin domain containing 3, NLRP3, is a multi-protein platform of recent discovery which plays a major role in the signaling pathways of the innate inflammatory response. The role of the activation of the NLRP3 inflammasome in cardiovascular pathologies is now well established and its metabolic priming by hyperglycemia could explain the greater seriousness of these pathologies in T2D patients due to an exacerbated inflammatory response. What is the effect of T2D status on the inflammatory response post ECC, mediated by the NLRP3 inflammasome, in patients after cardiac surgery?

Conditions

Inflammatory Response; Extracorporeal Circulation; Complications; Cardiac Surgery; Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Variation in the plasma concentration of cytokines IL-1β and IL18

  The variation in the plasma concentration of the two pro-inflammatory cytokines IL-1β and IL18, between a baseline level measured the day before the operating room (D-1) and 24 hours (D1) after cardiac surgery with ECC. The variation in their concentrations is measured between D-1 and D1 in order to assess the inflammatory response occurring in the first hours post ECC, and mediated by the NLRP3 inflammasome.

  48 hours

Secondary Outcomes (1)

• Compare the plasma levels of IL-1β and IL18

  Compare between Day-1 and Day 7

Other Outcomes (3)

• Compare the plasma concentration of mitochondrial (damage-associated molecular patterns) DAMPS

  Compare between Day-1 and Day 7

• Compare the level of activation of the NLRP3 inflammasome in circulating blood monocytes

  Compare between Day-1 and Day 7

• Compare the plasma concentration of reactive protein C (CRP) the level of activation of the NLRP3 inflammasome in circulating blood monocytes.

  Compare between Day-1 and Day 7

Study Arms (2)

Type 2 diabetes patients

EXPERIMENTAL

The variation in the plasma concentration of the two pro-inflammatory cytokines IL-1β and IL18, between a baseline level measured the day before the operating room (D-1) and 24 hours (D1) for TD2 patients after cardiac surgery with extracorporeal circulation .

Procedure: The role of the activation of the NLRP3 inflammasome after cardiac surgery

Non-diabetic type 2 patients

ACTIVE COMPARATOR

The variation in the plasma concentration of the two pro-inflammatory cytokines IL-1β and IL18, between a baseline level measured the day before the operating room (D-1) and 24 hours (D1) for non-diabetic type 2 patients after cardiac surgery with extracorporeal circulation

Procedure: The role of the activation of the NLRP3 inflammasome after cardiac surgery

Interventions

The role of the activation of the NLRP3 inflammasome after cardiac surgery PROCEDURE

Determine the effect on the inflammatory response post extracorporeal circulation mediated by the NLRP3 inflammasome, in patients after cardiac surgery

Non-diabetic type 2 patients; Type 2 diabetes patients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients between 18 and 75 years old
• Type 2 diabetic patients (WHO definition and American Diabetes Association) according to the following criteria: fasting blood glucose ≥ 7.0 mmol / L (fasting = no caloric proportion for at least 8 h) or glycosylated hemoglobin level HbA1c ≥ 6, 5% (in adults), or blood sugar 2 hours after ingestion of 75 g of glucose ≥ 11.1 mmol / L, or random blood sugar ≥ 11.1 mmol / L, either at any time of the day, without seeing at the time of the last meal.
• Patients undergoing aortocoronary bypass surgery or valve replacement with extracorporeal circulation at the university hospital of Martinique
• Patients able to receive and understand information related to research and blood samples taken during treatment
• Patients able to freely express informed and written consent
• Patients supported by french social security

You may not qualify if:

• Vulnerable people: people deprived of their liberty by a judicial or administrative decision, subjects admitted to a health or social protection establishment, major subjects under legal protection (guardianship or curatorship) or under the protection of justice, patients in situation emergency. Pregnant or lactating women, or women of childbearing potential without effective contraception. People with a state of health incompatible with the follow-up of the protocol (psychiatric disorders, uncontrolled disease), having cognitive disorders which do not allow the understanding of the study.
• Type 1 diabetic patient
• Patient who has a systemic inflammatory disease
• Patient who has an autoimmune disease
• Patient who has a cancer pathology
• Patient who has contraindications related to surgical operations in general such as general anesthesia

Sponsors & Collaborators

• University Hospital Center of Martinique: lead

Study Sites (1)

CHU de Martinique

Fort-de-France, 97261, Martinique

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Type 2 diabetics patients

Study Record Dates

• First Submitted: June 11, 2020
• First Posted: June 16, 2020
• Study Start: January 1, 2021
• Primary Completion: February 1, 2021
• Study Completion: March 1, 2021
• Last Updated: July 20, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1)