Genetic Variation and Immune Responses After Injury

Sepsis Clinical Trial

Official title:

Genetics of Innate Immune Response After Burn Trauma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00294697
• Other study ID #: 5K08GM071646-03
• Status: Recruiting
• Phase: N/A
• First received: February 21, 2006
• Last updated: August 23, 2010
• Start date: August 2003
• Est. completion date: October 2011

Study information

• Verified date: August 2010
• Source: National Institute of General Medical Sciences (NIGMS)
• Contact: Fernando A Rivera-Chavez, MD
• Phone: 214-648-3534
• Email: fernando.rivera[@]utsouthwestern.edu
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Federal Government
• Study type: Observational

Clinical Trial Summary

Our overall hypothesis is that genetic variations in innate immunity genes predispose patients to varying responses after injury by altering the systemic and local inflammatory responses. In addition, we hypothesize that these genetic differences are associated with different clinical outcomes

Description:

The goal of this research proposal is to identify relationships that exist between specific genetic markers, immune responses to injury and infection (sepsis), and post injury clinical outcomes. Specifically, we will investigate the clinical impact of mutations involved in the innate immune response, which likely influence host response. To accomplish this goal we will collect and analyze data from patients with acute thermal injury, the most quantitative inflammatory stimulus experienced by humans. In addition, we propose to further characterize the immunologic response parameters to injury and infection, and their role in complicated sepsis. In this way, we will identify parameters associated with unfavorable clinical outcomes, and determine how these parameters differ among individuals with different genotypes. We propose to 1) evaluate associations between candidate SNPs within the NOD2/RIP2 signaling pathway and clinical outcome following burn injury, 2) evaluate the functional effects of alternate alleles at candidate SNPs; finally 3), we will use genetically engineered animal models to determine whether mutations in the NOD2 or RIP2 genes alter myocardial signal transduction mechanisms shown to play a role in myocardial inflammation/dysfunction after burn trauma. These approaches should allow us to evaluate more extensively clinically relevant interactions between specific genetic polymorphisms, the cellular expression of immune mediators, and burn-induced immune dysfunction. The proposed research should uncover genetic and/or acute immune-inflammatory parameters that identify patients who are at "high risk" and could as a result make possible the targeted design of pharmacologic intervention strategies that will inhibit the toxic effects of LPS and other bacterial pathogen components without paralyzing the host immunity of patients

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: October 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria: All burn,trauma, or acute surgery victims admitted to the surgical, burn or trauma units within 24 hours of injury will be considered for inclusion.

Exclusion Criteria:severe immunosuppression, DNR, severe trauma, terminal diseases.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Burn
• Injury
• Pneumonia
• Sepsis
• Trauma

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center at Dallas	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of General Medical Sciences (NIGMS)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Barber RC, Aragaki CC, Rivera-Chavez FA, Purdue GF, Hunt JL, Horton JW. TLR4 and TNF-alpha polymorphisms are associated with an increased risk for severe sepsis following burn injury. J Med Genet. 2004 Nov;41(11):808-13. — View Citation

Rivera-Chavez FA, Peters-Hybki DL, Barber RC, Lindberg GM, Jialal I, Munford RS, O'Keefe GE. Innate immunity genes influence the severity of acute appendicitis. Ann Surg. 2004 Aug;240(2):269-77. — View Citation

Rivera-Chavez FA, Peters-Hybki DL, Barber RC, O'Keefe GE. Interleukin-6 promoter haplotypes and interleukin-6 cytokine responses. Shock. 2003 Sep;20(3):218-23. — View Citation

Rivera-Chavez FA, Wheeler H, Lindberg G, Munford RS, O'Keefe GE. Regional and systemic cytokine responses to acute inflammation of the vermiform appendix. Ann Surg. 2003 Mar;237(3):408-16. — View Citation