Mathematical Modeling of the Acute Inflammatory Response Following Injury

NCT00250523 | Unknown DMC

• 2 other identifiers: PRO 0801232P50GM053789-09
• Study Type: observational
• Target: 520
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to gather clinical and biologic information from severely injured patients to better understand and characterize the host response to injury and inflammation across several domains. This information may improve outcome prediction, improve clinical treatment of injured patients, and permit the construction of non-biologic computerized models of illness that can be utilized to represent the host response in future research efforts. This study is designed as the calibration of a mathematical model of this response with predictive capabilities. The central hypothesis governing this study is that adaptive immune elements are crucial to determining the outcome of complex inflammatory scenarios. We propose to test these hypotheses in the following interrelated Specific Aims: Specific Aim 1: To develop a robust mathematical model describing trauma/hemorrhage-induced inflammation in humans, its pathologic consequences, and possible therapies. Specific Aim 2: To translate the mathematical model to humans and create software aimed at individualized clinical decision-making. Specific Aim 3: To determine the prevalence of an IL-1 receptor-associated kinase (IRAK-1) variant haplotype located on the X-chromosome in an injured population, and to characterize differences in the pro-inflammatory response across gender, relative to the IRAK-1 haplotype. Specific Aim 4: To determine if increased arginase activity previously observed in isolated peripheral blood mononuclear cells of trauma patients is a consequence of the presence of contaminating activated granulocytes or a particular subset of an arginase positive monocyte subset.

Conditions

Trauma; Critical Illness

Keywords

trauma; critical illness; injury

Outcome Measures

Primary Outcomes (1)

• Multiple Organ Failure

  48 hours

Study Arms (2)

Traumatic injury

ICU Patients with blunt or penetrating injury

2

Healthy volunteers

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects to be recruited will consist of trauma patients and healthy volunteers:

You may qualify if:

• Present for treatment of their acute, blunt or penetrating injuries to the University of Pittsburgh Medical Center within 6 hours of injury
• Age greater than or equal to 18 years
• Intact cervical spinal cord
• Are admitted to the Intensive Care Unit

You may not qualify if:

• Anticipated survival \< 24 hrs
• Anticipated survival \< 28 days due to pre-existing condition
• Traumatic Brain injury (GCS ≤8 after ICU admission) AND brain CT abnormality within 12 hr of injury
• Inability to obtain consent from the subject or their legally authorized representative.
• Pre-existing immunosuppression
• Transplant recipient
• Chronic high doses of steroids (\>20 mg prednisone equivalents/day)
• Significant likelihood of high dose steroids (e.g. spinal cord injury)
• Oncolytic drug(s) therapy within the past 14 days
• Known HIV positive status and CD4 count \< 200 cells/mm3
• Admission to the ICU primary for substance withdrawal.
• Inability to obtain 1st blood sample within 24 hours of injury.
• Age greater than or equal to 18 years
• Weight \> 110 pounds
• no recent illness or infection in the last two weeks

Sponsors & Collaborators

• National Institute of General Medical Sciences (NIGMS): lead

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

For trauma injury cohort: The maximum blood volume collected over the 28 day period, if all samples are obtained, is approximately 90 cc. All standard precautions will be undertaken to assure minimal risk. Blood samples will be obtained for genetic analysis of inflammatory gene polymorphisms. We will collect whole blood, serum and white cells.

MeSH Terms

Conditions

Wounds and Injuries; Critical Illness

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jason L Sperry, MD

  UPMC Department of Surgery/Critical Care Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stacy D Stull, MS

CONTACT

412-692-4338; stullsd@upmc.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Surgery and Critical Care Medicine

Study Record Dates

• First Submitted: November 7, 2005
• First Posted: November 8, 2005
• Study Start: February 1, 2003
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2022
• Last Updated: March 2, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)