Characterisation of Endothelial Cells in Different Inflammatory Pathologies

Royal Surrey County Hospital NHS Foundation Trust105 enrolled

Overview

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?'

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

105

Conditions

Sepsis Vasoplegia

Interventions

Endothelial cell biopsyOTHER

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

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Locations (1)

Royal Surrey NHS Foundation Trust

Guildford, Surrey, United Kingdom

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: 2 years

Central Contacts

Ben Creagh-Brown, BM, PhD

CONTACT

+44 (0)1483 688 660 bencb@nhs.net

Charlie Piercy, MSc

CONTACT

+44 (0)1483 688 660 charles.piercy@nhs.net

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.