The Role of Dysfunctional HDL in Severe Sepsis

NCT02370186 | Completed

• 2 other identifiers: UFJ 2014-193IRB201702454
• Study Type: observational
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

Severe sepsis results in over 300,000 Emergency Department (ED) visits and 215,000 deaths annually in the US. Currently there are no effective drug therapies for sepsis. High density lipoprotein (HDL) has antioxidant, anti-inflammatory, and antithrombotic properties and is protective in sepsis. Its functions in sepsis are primarily mediated by its main apolipoprotein, Apo-A1, that: 1) neutralize potent bacterial toxins, 2) protect blood vessel walls from damage, 3) prevent tissue damage through antioxidant properties, and 4) mediate thymocyte apoptosis (critical for survival) and endogenous corticosteroid release. However, recent literature presents inconsistent data on HDL functionality and shows that HDL becomes non-functional during acute inflammatory states called dysfunctional HDL (Dys-HDL). Several causes for Dys-HDL have been hypothesized including the presence of Apo A1 polymorphisms, which may worsen the pathologic inflammatory response in sepsis and have been demonstrated in early sepsis, making Dys-HDL an unstudied potential early marker. This project aims to: 1) determine the presence of Dys-HDL in adult patients with early severe sepsis who present to the ED (Dys-HDL will be tested using a novel cell free assay and HDL Inflammatory Index will be measured), and 2) examine the relationship between Dys-HDL and cumulative organ dysfunction via Sequential Organ Failure Assessment (SOFA) score. Results of this study could establish Dys-HDL as an early disease marker for sepsis which is influential in the development of sepsis-induced organ dysfunction.

Conditions

Severe Sepsis; Septic Shock; Sepsis

Outcome Measures

Primary Outcomes (1)

• Dys-HDL in adult patients with early severe sepsis

  Measure Dys-HDL in adult patients with early severe sepsis who present to the ED.

  48 hours

Secondary Outcomes (1)

• Relationship between Dys-HDL and Cumulative Organ Dysfunction

  48 hours

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

Adults who present to one Emergency Department and who meet criteria for severe sepsis or septic shock.

You may qualify if:

• Patients 18 years and older with at least 2 of 4 SIRS criteria plus:
• lactate ≥ 2 mg/dL, AND
• SOFA Score ≥ 4\* (see Appendix A), or

You may not qualify if:

• Patients \<18 years of age
• Pregnant subjects
• No valid consent available
• Familial/genetic disorders of lipid metabolism

Sponsors & Collaborators

• University of Florida: lead
• University of Mississippi Medical Center: collaborator

Study Sites (1)

UF Health Jacksonville

Jacksonville, Florida, 32209, United States

Location

Related Publications (1)

• Guirgis FW, Dodani S, Leeuwenburgh C, Moldawer L, Bowman J, Kalynych C, Grijalva V, Reddy ST, Jones AE, Moore FA. HDL inflammatory index correlates with and predicts severity of organ failure in patients with sepsis and septic shock. PLoS One. 2018 Sep 14;13(9):e0203813. doi: 10.1371/journal.pone.0203813. eCollection 2018.

  PMID: 30216360 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Serum Plasma

MeSH Terms

Conditions

Sepsis; Shock, Septic

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Faheem W Guirgis, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 17, 2015
• First Posted: February 24, 2015
• Study Start: February 1, 2015
• Primary Completion: March 12, 2017
• Study Completion: March 12, 2017
• Last Updated: January 27, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)