Inflammation and the Host Response to Injury (Burns)

NCT00257244 | Completed DMC

• 2 other identifiers: 2 U54 GM062119_burnU54GM062119
• Study Type: observational
• Target: 280
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to help improve our understanding of the biology involved in the body's response to serious trauma or burn injury. The host response to trauma and burns is a collection of physiological and pathophysiological processes that depend critically upon the regulation of the human innate immune system, with particular emphasis on the inflammatory component of that system. No single research center or small group of centers has the capacity to delineate the integrated response of this complex biological system, which involves multiple molecular and genetic interactions that vary in time. Our proposal promotes the identification of important dynamic relationships that regulate the integration of this complex biological system, with the expectation that this understanding will ultimately impact the diagnosis, prognosis, and treatment of the hospitalized, severely injured patient.

Conditions

Trauma; Burns; Multiple Organ Failure

Keywords

Immunity, innate; Inflammation; Genomics; Proteomics

Outcome Measures

Primary Outcomes (3)

• Time to death

  Within two years of burn injury

• Change in gene expression after burn injury

  Up to two years after burn injury

• Number and type of complications

  Up to two years after burn injury

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Acute hospitalized burn patients

You may qualify if:

• Burn patients of all ages with 20% or greater of total body surface area burns that require surgical treatment
• Burn patients admitted to the burn unit within 96 hours (4 days) of burn injury

You may not qualify if:

• Injury caused by chemical agent
• Deep injury caused by conduction of electrical current or charge
• Decision not to treat due to severity of injury
• Anoxic brain injury that is not expected to result in complete recovery
• Associated multiple injuries exclusive of burns (ISS \>=25)
• Pre-morbid condition: Severe congestive heart failure (measured ejection fraction \<20%)
• Pre-morbid condition: Malignancy currently under treatment
• Pre-morbid condition: Medical condition requiring systemic glucocorticoid treatment
• Pre-morbid condition: current systemic immunosuppression for organ transplant or chronic inflammatory condition

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (4)

Loyola University Medical Center at Loyola in Chicago

Maywood, Illinois, 60153, United States

Location

Southwestern Medical Center at University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

University of Texas at Galveston-Shriners Burn Hospital- Galveston

Galveston, Texas, 77550, United States

Location

Harborview Medical Center at University of Washington

Seattle, Washington, 98104, United States

Location

Related Publications (19)

• Brownstein BH, Logvinenko T, Lederer JA, Cobb JP, Hubbard WJ, Chaudry IH, Remick DG, Baker HV, Xiao W, Mannick JA. Commonality and differences in leukocyte gene expression patterns among three models of inflammation and injury. Physiol Genomics. 2006 Feb 14;24(3):298-309. doi: 10.1152/physiolgenomics.00213.2005. Epub 2005 Dec 20.

  PMID: 16478828 BACKGROUND

• Silver GM, Klein MB, Herndon DN, Gamelli RL, Gibran NS, Altstein L, McDonald-Smith GP, Tompkins RG, Hunt JL; Inflammation and the Host Response to Trauma, Collaborative Research Program. Standard operating procedures for the clinical management of patients enrolled in a prospective study of Inflammation and the Host Response to Thermal Injury. J Burn Care Res. 2007 Mar-Apr;28(2):222-30. doi: 10.1097/BCR.0B013E318031AA44.

  PMID: 17351437 BACKGROUND

• Lederer JA, Brownstein BH, Lopez MC, Macmillan S, Delisle AJ, Macconmara MP, Choudhry MA, Xiao W, Lekousi S, Cobb JP, Baker HV, Mannick JA, Chaudry IH; Inflammation and the Host Response to Injury Collaborative Research Program Participants. Comparison of longitudinal leukocyte gene expression after burn injury or trauma-hemorrhage in mice. Physiol Genomics. 2008 Feb 19;32(3):299-310. doi: 10.1152/physiolgenomics.00086.2007. Epub 2007 Nov 6.

  PMID: 17986522 BACKGROUND

• Klein MB, Silver G, Gamelli RL, Gibran NS, Herndon DN, Hunt JL, Tompkins RG; Inflammation and the Host Response to Injury Investigators. Inflammation and the host response to injury: an overview of the multicenter study of the genomic and proteomic response to burn injury. J Burn Care Res. 2006 Jul-Aug;27(4):448-51. doi: 10.1097/01.BCR.0000227477.33877.E6.

  PMID: 16819346 RESULT

• Klein MB, Hayden D, Elson C, Nathens AB, Gamelli RL, Gibran NS, Herndon DN, Arnoldo B, Silver G, Schoenfeld D, Tompkins RG. The association between fluid administration and outcome following major burn: a multicenter study. Ann Surg. 2007 Apr;245(4):622-8. doi: 10.1097/01.sla.0000252572.50684.49.

  PMID: 17414612 RESULT

• Russom A, Sethu P, Irimia D, Mindrinos MN, Calvano SE, Garcia I, Finnerty C, Tannahill C, Abouhamze A, Wilhelmy J, Lopez MC, Baker HV, Herndon DN, Lowry SF, Maier RV, Davis RW, Moldawer LL, Tompkins RG, Toner M; Inflammation and Host Response to Injury Large Scale Collaborative Research Program. Microfluidic leukocyte isolation for gene expression analysis in critically ill hospitalized patients. Clin Chem. 2008 May;54(5):891-900. doi: 10.1373/clinchem.2007.099150. Epub 2008 Mar 28.

  PMID: 18375483 RESULT

• Kotz KT, Xiao W, Miller-Graziano C, Qian WJ, Russom A, Warner EA, Moldawer LL, De A, Bankey PE, Petritis BO, Camp DG 2nd, Rosenbach AE, Goverman J, Fagan SP, Brownstein BH, Irimia D, Xu W, Wilhelmy J, Mindrinos MN, Smith RD, Davis RW, Tompkins RG, Toner M; Inflammation and the Host Response to Injury Collaborative Research Program. Clinical microfluidics for neutrophil genomics and proteomics. Nat Med. 2010 Sep;16(9):1042-7. doi: 10.1038/nm.2205. Epub 2010 Aug 29.

  PMID: 20802500 RESULT

• Xiao W, Mindrinos MN, Seok J, Cuschieri J, Cuenca AG, Gao H, Hayden DL, Hennessy L, Moore EE, Minei JP, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Brownstein BH, Mason PH, Baker HV, Finnerty CC, Jeschke MG, Lopez MC, Klein MB, Gamelli RL, Gibran NS, Arnoldo B, Xu W, Zhang Y, Calvano SE, McDonald-Smith GP, Schoenfeld DA, Storey JD, Cobb JP, Warren HS, Moldawer LL, Herndon DN, Lowry SF, Maier RV, Davis RW, Tompkins RG; Inflammation and Host Response to Injury Large-Scale Collaborative Research Program. A genomic storm in critically injured humans. J Exp Med. 2011 Dec 19;208(13):2581-90. doi: 10.1084/jem.20111354. Epub 2011 Nov 21.

  PMID: 22110166 RESULT

• Finnerty CC, Jeschke MG, Herndon DN, Gamelli R, Gibran N, Klein M, Silver G, Arnoldo B, Remick D, Tompkins RG; Investigators of the Inflammation and the Host Response Glue Grant. Temporal cytokine profiles in severely burned patients: a comparison of adults and children. Mol Med. 2008 Sep-Oct;14(9-10):553-60. doi: 10.2119/2007-00132.Finnerty.

  PMID: 18548133 RESULT

• Qian WJ, Liu T, Petyuk VA, Gritsenko MA, Petritis BO, Polpitiya AD, Kaushal A, Xiao W, Finnerty CC, Jeschke MG, Jaitly N, Monroe ME, Moore RJ, Moldawer LL, Davis RW, Tompkins RG, Herndon DN, Camp DG, Smith RD; Inflammation and the Host Response to Injury Large Scale Collaborative Research Program. Large-scale multiplexed quantitative discovery proteomics enabled by the use of an (18)O-labeled "universal" reference sample. J Proteome Res. 2009 Jan;8(1):290-9. doi: 10.1021/pr800467r.

  PMID: 19053531 RESULT

• Qian WJ, Petritis BO, Kaushal A, Finnerty CC, Jeschke MG, Monroe ME, Moore RJ, Schepmoes AA, Xiao W, Moldawer LL, Davis RW, Tompkins RG, Herndon DN, Camp DG 2nd, Smith RD; Inflammation and the Host Response to Injury Large Scale Collaborative Research Program. Plasma proteome response to severe burn injury revealed by 18O-labeled "universal" reference-based quantitative proteomics. J Proteome Res. 2010 Sep 3;9(9):4779-89. doi: 10.1021/pr1005026.

  PMID: 20698492 RESULT

• Jeschke MG, Finnerty CC, Herndon DN, Song J, Boehning D, Tompkins RG, Baker HV, Gauglitz GG. Severe injury is associated with insulin resistance, endoplasmic reticulum stress response, and unfolded protein response. Ann Surg. 2012 Feb;255(2):370-8. doi: 10.1097/SLA.0b013e31823e76e7.

  PMID: 22241293 RESULT

• Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, Richards DR, McDonald-Smith GP, Gao H, Hennessy L, Finnerty CC, Lopez CM, Honari S, Moore EE, Minei JP, Cuschieri J, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Jeschke MG, Klein MB, Gamelli RL, Gibran NS, Brownstein BH, Miller-Graziano C, Calvano SE, Mason PH, Cobb JP, Rahme LG, Lowry SF, Maier RV, Moldawer LL, Herndon DN, Davis RW, Xiao W, Tompkins RG; Inflammation and Host Response to Injury, Large Scale Collaborative Research Program. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3507-12. doi: 10.1073/pnas.1222878110. Epub 2013 Feb 11.

  PMID: 23401516 RESULT

• Finnerty CC, Jeschke MG, Qian WJ, Kaushal A, Xiao W, Liu T, Gritsenko MA, Moore RJ, Camp DG 2nd, Moldawer LL, Elson C, Schoenfeld D, Gamelli R, Gibran N, Klein M, Arnoldo B, Remick D, Smith RD, Davis R, Tompkins RG, Herndon DN; Investigators of the Inflammation and the Host Response Glue Grant. Determination of burn patient outcome by large-scale quantitative discovery proteomics. Crit Care Med. 2013 Jun;41(6):1421-34. doi: 10.1097/CCM.0b013e31827c072e.

  PMID: 23507713 RESULT

• Warren HS, Tompkins RG, Mindrinos MN, Xiao W, Davis RW. Reply to Cauwels et al.: Of men, not mice, and inflammation. Proc Natl Acad Sci U S A. 2013 Aug 20;110(34):E3151. doi: 10.1073/pnas.1308943110. No abstract available.

  PMID: 24137663 RESULT

• Jeschke MG, Finnerty CC, Emdad F, Rivero HG, Kraft R, Williams FN, Gamelli RL, Gibran NS, Klein MB, Arnoldo BD, Tompkins RG, Herndon DN. Mild obesity is protective after severe burn injury. Ann Surg. 2013 Dec;258(6):1119-29. doi: 10.1097/SLA.0b013e3182984d19.

  PMID: 23877367 RESULT

• Klein MB, Goverman J, Hayden DL, Fagan SP, McDonald-Smith GP, Alexander AK, Gamelli RL, Gibran NS, Finnerty CC, Jeschke MG, Arnoldo B, Wispelwey B, Mindrinos MN, Xiao W, Honari SE, Mason PH, Schoenfeld DA, Herndon DN, Tompkins RG; Inflammation and Host Response to Injury, and Large-Scale Collaborative Research Program. Benchmarking outcomes in the critically injured burn patient. Ann Surg. 2014 May;259(5):833-41. doi: 10.1097/SLA.0000000000000438.

  PMID: 24722222 RESULT

• Tompkins RG. Survival from burns in the new millennium: 70 years' experience from a single institution. Ann Surg. 2015 Feb;261(2):263-8. doi: 10.1097/SLA.0000000000000623.

  PMID: 24670865 RESULT

• Warren HS, Tompkins RG, Moldawer LL, Seok J, Xu W, Mindrinos MN, Maier RV, Xiao W, Davis RW. Mice are not men. Proc Natl Acad Sci U S A. 2015 Jan 27;112(4):E345. doi: 10.1073/pnas.1414857111. Epub 2014 Dec 24. No abstract available.

  PMID: 25540422 RESULT

Related Links

• Information about the study and its goals. Contains links to study related publications, resources, and participating institutions

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma, blood leukocyte nucleic acids (RNA), solid tissue nucleic acids (only RNA, no DNA)

MeSH Terms

Conditions

Wounds and Injuries; Burns; Multiple Organ Failure; Inflammation

Condition Hierarchy (Ancestors)

Shock; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ronald G. Tompkins, MD, ScD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Burns Service

Study Record Dates

• First Submitted: November 18, 2005
• First Posted: November 22, 2005
• Study Start: April 1, 2004
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2018
• Last Updated: March 7, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will share

Locations

US (4)