Clinical trial NCT04576819: Role and Mechanisms of Lipid and Lipoprotein Dysregulation in Sepsis
Official title: Role and Mechanisms of Lipid and Lipoprotein Dysregulation in Sepsis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sepsis
Shock, Septic
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Institute of General Medical Sciences (NIGMS)
First posted: 2020-10-06
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Chronic Critical Illness or Early Death
timeFrame: 14 days from sepsis onset
Secondary outcomes:
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Faheem Guirgis, MD
role: PRINCIPAL_INVESTIGATOR
References: