The Role of Immune Semaphorins in Steatotic Liver Disease and Sepsis (SepsisFAT)

September 1, 2023 updated by: University Hospital for Infectious Diseases, Croatia
The impact of the complex liver immunological network on sepsis outcome is largely unknown. Steatotic liver disease (SLD) is the most common chronic liver disease with prevalence of 25% in European countries. The question remains whether patients with SLD are more prone to bacterial infections and what is the impact of persistent liver inflammation to the systemic response to infection, sepsis course and outcomes. Semaphorins are a large family of secreted and membrane-bound biological response modifiers present in many organ systems that are associated with SLD and development of fibrosis, but also might regulate systemic immune responses in sepsis. This study will investigate the association of semaphorins with sepsis outcomes in patients with SLD.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The liver, with its ability to produce acute phase proteins, complement and cytokines, plays a central role in regulating inflammation. A balanced pro- and anti-inflammatory liver response results in bacterial clearance and resolution of inflammation. Steatotic liver disease (SLD) is the most common chronic liver disease associated with systemic changes in immune response. Although there are numerous immunological links between sepsis and SLD, there is a significant gap in knowledge regarding the role of SLD in sepsis. Semaphorins were recently recognized as one of the key regulators of immune responses; while some suppress immune cells activation, proliferation and production of inflammatory cytokines, others stimulate immune responses. Semaphorins were recently shown to be associated with pathogenesis of viral hepatitis, SLD and progression of fibrosis. However, their role in sepsis is unknown. The hypothesis of this project is that semaphorins are regulators of inflammation in patients with SLD that have impact on sepsis outcome.

Study Type

Observational

Enrollment (Estimated)

160

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Croatia
      • Zagreb, Croatia, 10000
        • Recruiting
        • University Hospital for Infectious Diseases Zagreb
        • Sub-Investigator:
          • Branimir Gjurasin, MD
        • Sub-Investigator:
          • Juraj Krznaric, MD
        • Sub-Investigator:
          • Lara Samadan
        • Sub-Investigator:
          • Nina Vrsaljko, MD
        • Contact:
          • Neven Papic, MD, PhD
          • Phone Number: +38512826222
          • Email: npapic@bfm.hr
        • Principal Investigator:
          • Neven Papic, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

All adult patients admitted at three clinical departments at UHID that meet inclusion criteria will be offered to participate in the study during a 24-month period.

Description

Inclusion Criteria:

  • 2 or more SIRS (Systemic Inflammatory Response Syndrome) criteria (1. Hyperthermia >38.3°C or Hypothermia <36°C; 2. Tachycardia >90 bpm; 3. Tachypnea >20 bpm; 3. Leukocytosis (>12,000 μL-1) or Leukopenia (<4,000 μL-1))
  • clinical suspicion of sepsis
  • enrolled within 24 hours of hospital admission

Exclusion Criteria:

  • no consent
  • immunosuppression
  • malignancies
  • immune diseases
  • pregnancy
  • HIV infection
  • presence of chronic liver disease
  • consumption of alcohol > 20 g/day

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Sepsis
Patients hospitalized due to the sepsis
Diagnostic test: Measurement of serum semaphorin concentrations
Semaphorin concentration will be measured in patient sera by ELISA.
Diagnostic test: Screening for the components of metabolic syndrome
Anthropometric measures including height, weight, waist circumference and hip circumference will be measured in all patients. Results of the routine laboratory tests as part of the standard diagnostic procedure will be collected: CRP, leukocyte count, ratio neutrophils and lymphocytes, hemoglobin, platelet count, urea, creatinine, bilirubin, AST, ALT, GGT, ALP, albumins, fasting glucose.
Diagnostic test: Evaluation of the degree of steatosis
The degree of steatosis will be estimated using the ultrasound and a method for grading steatosis will be measuring the degree of ultrasound attenuation by hepatic fat using a process based on simultaneous transient elastography (TE) which measures the degree of steatosis.
Diagnostic test: Measurement of inflammatory cytokines
A panel of pro- and anti-inflammatory markers will be determined by flow cytometer microsphere-based assay.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Detection of semaphorins in patients with sepsis and SLD
Time Frame: 24 months
Measurement of semaphorins concentration in serum of patients with SLD and sepsis by enzyme-linked immunosorbent assay (ELISA)
24 months
Impact of SLD on sepsis outcomes
Time Frame: 24 months
Analysis of the impact of SLD and steatosis grade (grade 1 - mild steatosis, 2 - moderate, 3 - severe steatosis) on sepsis complications and outcomes.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital for Infectious Diseases, Croatia

Collaborators

Croatian Science Foundation

Investigators

  • Principal Investigator: Neven Papic, MD, PhD, School of Medicine, University of Zagreb

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2022

Primary Completion (Estimated)

February 28, 2024

Study Completion (Estimated)

March 1, 2024

Study Registration Dates

First Submitted

August 27, 2023

First Submitted That Met QC Criteria

August 27, 2023

First Posted (Actual)

September 1, 2023

Study Record Updates

Last Update Posted (Actual)

September 7, 2023

Last Update Submitted That Met QC Criteria

September 1, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UHID-08

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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