Characterisation of Endothelial Cells in Different Inflammatory Pathologies (JEDI-2)

The goal of this observational study is to characterise changes in gene expression in endothelial cells in patients with either sepsis or post major abdominal surgery.

The main question we plan to answer is: 'What molecular pathways are differentially expressed during inflammatory pathologies?'

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Vasoplegia
• Intervention / Treatment: Other: Endothelial cell biopsy

Detailed Description

The immune system is a complex network of cells and molecules that protects the body from infection and injury. When the immune system is activated, it produces inflammation, which is a natural response to help heal the body. However, too much inflammation can be harmful and lead to serious complications, such as sepsis, low blood pressure, organ failure and death.

The interaction of cells that line the blood vessels (endothelial cells, EC) with the immune system, is believed to be the root cause of these symptoms. When exposed to inflammation, the instructional molecules (RNA) inside the EC change. This leads to a change of operation promoting the severe symptoms previously mentioned.

Researchers have developed new safe techniques to collect these cells from the blood vessels of patients to study disorders like diabetes, heart disease and stroke. This technique involves gently inserting a metal guidewire into an arm vein to collect ECs.

This study plans to collect ECs from patients undergoing surgery or admitted to intensive care. We also plan to collect control samples from healthy volunteers. Samples will be collected over the duration of the patients to RSFT. The RNA will be removed from the cells and counted to highlight changes in instructions in the cells.

Data from this study will potentially highlight new pathways involved in inflammation and help classify how some patients will react to current treatments. To obtain this data, this study will be split into 2 parts. Part 1 focuses on collecting one sample from a patient when they are at their most unwell states and comparing that to a sample from a healthy person. Part 2 will focus on key mRNA molecules identified during Part 1 and identifying how their expression changes over time.

• Study Type: Observational
• Enrollment (Estimated): 105

Contacts and Locations

• Study Contact: Name: Ben Creagh-Brown, BM, PhD; Phone Number: +44 (0)1483 688 660; Email: bencb@nhs.net
• Study Contact Backup: Name: Charlie Piercy, MSc; Phone Number: +44 (0)1483 688 660; Email: Charles.piercy@nhs.net

Study Locations

• United Kingdom
  • Surrey
    • Guildford, Surrey, United Kingdom, GU27XX
      • Recruiting
      • Royal Surrey NHS Foundation Trust
      • Contact: Ben Creagh-Brown, BM, PhD; Phone Number: +44 (0)1483 688 660; Email: bencb@nhs.net
      • Contact: Charlie Piercy, MSc; Phone Number: +44 (0)1483 688 660; Email: Charles.piercy@nhs.net
      • Principal Investigator: Charlie Piercy, MSc

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Surgical cohort This cohort will predominantly be made up predominantly of patients undergoing major abdominal surgery (HPB, Gynae Onc and Colorectal) requiring recovery in ICU as part of their cancer treatment.

Critically unwell cohort This cohort will be made up of emergency admissions to ICU for patients requiring additional organ support.

Description

Inclusion Criteria:

Healthy volunteer

• Adult ≥ 18 years
• Able and willing to give consent

Surgical patients

• Adult ≥ 18 years
• Patients admitted to RSFT for planned major surgery

Critically ill patients

• Adult ≥ 18 years
• Emergency admission to ICU at RSFT
• Meets the sepsis 3.0 definition

Exclusion Criteria:

Healthy volunteer

• Not currently a patient within the hospital
• Absence of inflammatory diseases and disorders including but not limited to arthritis, peripheral artery disease, vasculitis, diabetes, cardiovascular disease and CKD.
• Not on immunomodulatory medications, such as corticosteroids
• History of recent major trauma within the last 2 months (e.g., surgery or injury requiring hospitalisation)

Surgical patients

• Patients with restricted liberty, prisoners or under legal protection
• Anticipated prohibitively difficult venous cannulation
• Presenting with inflammatory diseases and disorders including but not limited to arthritis, peripheral artery disease, vasculitis, sepsis, diabetes with end organ damage, cardiovascular disease and CKD
• Currently prescribed immunomodulatory medication or immunocompromised
• Received chemotherapy within 2 weeks of predicted sampling
• Receiving vasopressor support prior to surgery
• History of recent major trauma within the last 2 months (e.g., surgery or injury requiring hospitalisation)

Critically ill patients

• Patients with restricted liberty, prisoners or under legal protection• Anticipated prohibitively difficult venous cannulation
• Presenting with inflammatory diseases and disorders including but not limited to arthritis, peripheral artery disease, vasculitis, diabetes with end organ damage, cardiovascular disease and CKD.
• Currently prescribed immunomodulatory medication or immunocompromised
• Received chemotherapy within 2 weeks of predicted sampling.
• History of recent major trauma within the last 2 months (e.g., surgery or injury requiring hospitalisation)

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Part 1 - control patients; 25 healthy volunteers 1 X Endothelial cell biopsy	Other: Endothelial cell biopsy; Endothelial cell sample collected from the antecubital fossa of patients. A vein in the antecubital fossa is cannulated with a 20 g valveless cannula. A metal guidewire is then passed into the vessel to collect endothelial cells for analysis
Part 1 - surgical patients; 20 surgical patients 1 X Endothelial cell biopsy Samples collected at 24 hours post knife to skin to capture peak inflammation	Other: Endothelial cell biopsy; Endothelial cell sample collected from the antecubital fossa of patients. A vein in the antecubital fossa is cannulated with a 20 g valveless cannula. A metal guidewire is then passed into the vessel to collect endothelial cells for analysis
Part 1 - sepsis patients; 20 sepsis patients 1 X Endothelial cell biopsy Samples collected on admission to ICU	Other: Endothelial cell biopsy; Endothelial cell sample collected from the antecubital fossa of patients. A vein in the antecubital fossa is cannulated with a 20 g valveless cannula. A metal guidewire is then passed into the vessel to collect endothelial cells for analysis
Part 2 - surgical patients; 20 surgical patients 3 X Endothelial cell biopsy Samples collected pre-surgery, 24 hours and 48 hours post knife to skin	Other: Endothelial cell biopsy; Endothelial cell sample collected from the antecubital fossa of patients. A vein in the antecubital fossa is cannulated with a 20 g valveless cannula. A metal guidewire is then passed into the vessel to collect endothelial cells for analysis
Part 2 - sepsis patients; 20 sepsis patients 3 X Endothelial cell biopsy Samples collected on admission, 24 hours and 48 hours post admission to ICU	Other: Endothelial cell biopsy; Endothelial cell sample collected from the antecubital fossa of patients. A vein in the antecubital fossa is cannulated with a 20 g valveless cannula. A metal guidewire is then passed into the vessel to collect endothelial cells for analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differential gene expression in endothelial cells	Using RNA extracted from the two patient cohorts and controls in part 1, we plan to use RNA-SEQ to identify differentially expressed genes. Once we have identified genes we believe to be critically involved with endothelial dysfunction, we will then perform serial sampling on an additional two groups of patients and using qRT-PCR to analyse gene expression changes.	2 years

Collaborators and Investigators

• Sponsor: Royal Surrey County Hospital NHS Foundation Trust
• Collaborators: University of Surrey

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2024
• Primary Completion (Estimated): July 17, 2026
• Study Completion (Estimated): November 12, 2026

Study Registration Dates

• First Submitted: September 18, 2024
• First Submitted That Met QC Criteria: September 23, 2024
• First Posted (Actual): September 25, 2024

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Vasoplegia
• Other Study ID Numbers: 24SURN320251

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