Role and Mechanisms of Lipid and Lipoprotein Dysregulation in Sepsis

Lipids and lipoproteins (cholesterol and lipid metabolites) are present in sepsis and are highly biologically active regulators of inflammation, but currently the changes in lipid and lipoprotein homeostasis during sepsis are not well understood. This project will investigate the changes in lipid and lipoprotein function, oxidation, metabolites, and changes in gene expression to further our understanding of dysregulated lipid and lipoprotein metabolism in sepsis. We will analyze a bank of samples and make associations with important clinical outcomes (early death, chronic critical illness and sepsis recidivism) as supported by our published work, and will confirm our findings in a small prospective cohort of sepsis patients.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Shock, Septic

Detailed Description

This study will use biobanked samples from a diverse cohort of 165 sepsis patients (UF Jacksonville and UF Gainesville) and will confirm findings in a small prospective cohort of 50 patients. The following will be tested in patient samples:

Aim 1: Test and compare HDL and LDL function (oxidation/transport) in sepsis patients by clinical outcomes of rapid recovery, early death, CCI, and sepsis recidivism.

Aim 2: Determine the changes in lipid homeostasis and patterns of inflammation that occur in sepsis patients by outcome.

Aim 3: Characterize cholesterol & lipoprotein-specific metabolic gene expression in whole blood leukocytes and peripheral blood mononuclear cells from sepsis patients.

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

• Study Contact: Name: Morgan Henson, MPH; Phone Number: 904-244-4986; Email: Morgan.Henson@jax.ufl.edu
• Study Contact Backup: Name: Amy Kennedy; Phone Number: 904-244-4986; Email: Amy.Kennedy@jax.ufl.edu

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Recruiting
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients meeting the Sepsis-3 definition of sepsis and being treated with institutional evidence-based care bundles.

Description

Inclusion criteria:

• Patients meeting the Sepsis-3 definition of sepsis or septic shock
• Treatment with an institutional, evidence-based guideline management bundle for sepsis within 24 hrs of sepsis recognition
• Sequential organ failure assessment (SOFA) score will be used for organ failure assessment.

Exclusion criteria:

• a) alternative/confounding diagnosis causing shock (e.g., myocardial infarction or pulmonary embolus)
• b) uncontrollable source of sepsis (e.g., irreversible disease state such as unresectable dead bowel)
• c) advanced directives limiting resuscitative efforts
• d) organ transplant recipient on immunosuppressive agents
• e) known pregnancy
• f) inability to obtain informed consent
• g) HIV/AIDS with CD4 count < 200, h) absolute neutrophil count < 500. These criteria are justified by numerous prior studies.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Sepsis cohort; Inclusion criteria; Patients meeting the Sepsis-3 definition of sepsis or septic shock (the sequential organ failure assessment (SOFA) score will be used for organ failure assessment for Sepsis-3 criteria); Treatment with an institutional, evidence-based guideline management bundle for sepsis; Within 24 hrs of sepsis recognition Exclusion criteria: alternative/confounding diagnosis causing shock (e.g., myocardial infarction or pulmonary embolus),; uncontrollable source of sepsis (e.g., irreversible disease state such as unresectable dead bowel),; advanced directives limiting resuscitative efforts,; organ transplant recipient on immunosuppressive agents,; known pregnancy,; inability to obtain informed consent,; HIV/AIDS with CD4 count < 200,; absolute neutrophil count < 500

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chronic Critical Illness or Early Death	CCI defined as admission to ICU > 14 days total with organ dysfunction, Early death defined as death within 14 days of hospital admission	14 days from sepsis onset

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Faheem Guirgis, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2020
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: September 25, 2020
• First Submitted That Met QC Criteria: September 30, 2020
• First Posted (Actual): October 6, 2020

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Sepsis; Toxemia; Shock, Septic
• Other Study ID Numbers: IRB201903081-N; 1R01GM133815-01A1 (U.S. NIH Grant/Contract)

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