Adiposity and Immunometabolism in Sepsis

NCT06307509 | Not Yet Recruiting

• 1 other identifier: GN23AN097
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity has been shown to increase adverse outcomes in some critically ill patients e.g. those with COVID-19. For patients with sepsis this association is less clear cut but there is evidence that body fat distribution, resulting from impaired subcutaneous adipose tissue function, is associated with adverse clinical outcomes in critical care. The investigators aim to study subcutaneous adipose tissue function in lean and obese sepsis patients in critical care and compare that to healthy controls. First, the study will investigate differences in adipose tissue function (inflammation and mitochondrial function) related to obesity. Second, the investigators will examine whether lean critically ill patients with sepsis have enhanced adipose tissue inflammation and mitochondrial dysfunction compared to lean controls and whether this is further exacerbated by obesity. Patients will be either undergoing emergency abdominal surgery, or will have been admitted to a critical care unit with a diagnosis of sepsis. The investigators will collect blood and adipose tissue biopsies from the patients, and these will be analysed for markers of inflammation and of mitochondrial function. The aim is to better understand the relationship between obesity, inflammation, mitochondrial dysfunction and sepsis. The investigators hope that this may improve the understanding of the pathophysiology of sepsis and allow more targeted interventions for patients based on differences in their baseline metabolic state.

Conditions

Obesity; Sepsis

Keywords

obesity; adipose tissue; sepsis; critical illness

Outcome Measures

Primary Outcomes (1)

• Difference in adipocyte cytokine secretion between patients with sepsis, and patients without sepsis, and between SAT and VAT samples

  Cytokine quantitation from adipose tissue samples will be carried out using using magnetic bead multiple arrays or by commercial ELISA to investigate for any possible differences between patients with and without sepsis, and between SAT and VAT samples

  Within 72 hours of admission to ICU

Secondary Outcomes (7)

• Differences in adipocyte size

  Within 72 hours of admission to ICU

• Differences in mitochondrial morphology

  Within 72 hours of admission to ICU

• Differences in adipocyte pro-inflammatory gene expression

  Within 72 hours of admission to ICU

• Differences in adipocyte mitochondrial number

  Within 72 hours of admission to ICU

• Differences in adipocyte mitochondrial viability

  Within 72 hours of admission to ICU

Study Arms (2)

ICU patients with sepsis

Patients admitted to the Intensive Care Unit with a primary diagnosis of sepsis. They will have subcutaneous adipose tissue samples taken by needle aspiration, and blood samples taken.

Other: Diagnosis of sepsis

Surgical patients with sepsis

Patients undergoing emergency laparotomy with a diagnosis of sepsis will have subcutaneous and visceral adipose tissue samples taken intra-operatively, and blood samples taken.

Other: Diagnosis of sepsis

Interventions

Diagnosis of sepsis OTHER

Patients will be recruited on the basis of a diagnosis of sepsis, as this is the exposure of interest

ICU patients with sepsis; Surgical patients with sepsis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients admitted to a critical care unit with a diagnosis of sepsis will be screened using the IntelliSpace Critical Care and Anesthesia electronic patient record, after identification and discussion with the clinical team. Patients undergoing emergency surgery will be screened using the Opera theatre management system, after identification and discussion with the clinical teams.

You may qualify if:

• For patients in a critical care unit:
• Diagnosis of sepsis by the criteria set out in the Sepsis-3 guidelines:
• Suspected diagnosis of infection
• Acute change in Sequential Organ Failure Assessment (SOFA) of ≥2
• For patients undergoing an operation:
• Undergoing emergency abdominal surgery
• Diagnosis of sepsis by the criteria set out in the Sepsis-3 guidelines:
• Suspected diagnosis of infection
• Acute change in Sequential Organ Failure Assessment (SOFA) of ≥2

You may not qualify if:

• Patient moribund and death is perceived to be imminent
• ≥48 hours from diagnosis with sepsis
• Pregnancy
• Prisoners
• Receiving treatment-dose anticoagulant medication
• Declined consent

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead
• University of Glasgow: collaborator

Study Sites (1)

Department of Critical Care Medicine, Queen Elizabeth University Hospital

Glasgow, G51 4TF, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Frozen subcutaneous and visceral adipose tissue samples, isolated adipocytes and serum samples will be retained and stored as per University of Glasgow protocols

MeSH Terms

Conditions

Obesity; Sepsis; Critical Illness

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Disease Attributes

Study Officials

• Malcolm Watson, MBChB, PhD

  NHS Greater Glasgow & Clyde

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Malcolm AB Sim, MBChB, MD

CONTACT

+44(0)1412112470; Malcolm.Sim@ggc.scot.nhs.uk

Maximilian R Ralston, MBChB

CONTACT

+44(0)1414523094; Maximilian.Ralston@ggc.scot.nhs.uk

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2024
• First Posted: March 13, 2024
• Study Start: March 1, 2024
• Primary Completion: April 30, 2025
• Study Completion: July 31, 2025
• Last Updated: March 13, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)