The Role of Angiopoietin, Tie-2, and Vascular Endothelial Growth Factor (VEGF) in Sepsis-Induced Multiple Organ Dysfunction Syndrome (MODS)

The Role of Angiopoietin, Angiopoietin Receptor Tie-2, and Vascular Endothelial Growth Factor in Sepsis-Induced Multi-Organ Dysfunction Syndrome

This study is designated to determine serum concentrations of inflammatory mediators Ang-1, Ang-2, Ang-1/Ang-2 ratio, and Tie-2 in patients with sepsis-induced MODS and to investigate the association among increased permeability, inflammatory mediators, and these serum mediators in development of organ failure.

Study Overview

• Status: Unknown
• Conditions: Sepsis; Multiple Organ Dysfunction Syndrome

Detailed Description

Multiple Organ Dysfunction Syndrome (MODS) frequently leads to death in patients with sepsis. Our previous work has demonstrated that endothelial injury is closely associated with MODS development and mortality in septic patients. The sepsis-induced damage of endothelial cell membrane gives rise to increased capillary permeability. Evidence suggests that increased capillary permeability in patients with sepsis was associated with higher incidence of MODS and death during the ICU stay than those with decreased permeability. Angiopoietin (Ang) system is the key mediator for maintaining capillary permeability. Ang-2 triggers an inflammatory response and inducing permeability by activating the endothelium. In contrast, Ang-1 is anti-inflammatory, can inhibit adhesion molecule expression and attenuate permeability increase in different stimuli. The disrupted angiopoietin system has been reported in patients with sepsis, but the association between angiotension and MODS in septic patients has not been well addressed.

This study is designated to determine serum concentrations of Ang-1, Ang-2, Ang-1/Ang-2 ratio, and Tie-2 in patients with sepsis-induced MODS and to investigate the association among increased permeability, inflammatory mediators,autonomic dysfunction, and these serum mediators in development of organ failure. In addition, the study will incubate endothelial cells with septic patients' serum or tumor necrosis factor (TNF)-alfa, and determine the effects of ang-1 administration and blockade of ang-2 on disruption of endothelial cell structure, permeability increase, and expression of adhesion molecules. The study will also determine the signaling pathways and altered NF-kB dimmer composition that is responsible for the inhibitory effect for ang-1 administration on TNF-alfa-induced intercellular adhesion molecule (ICAM)-1 expression on endothelial surface.

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

Study Locations

• Taiwan
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hospital
    • Contact: Shu-Min Lin, MD; Phone Number: 8467 88633281200; Email: smlin100@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

patients admitted to ICU due to sepsis

Description

Inclusion Criteria:

• Patients must have known origin of infection plus at least 2 of the following criteria of systemic inflammatory response syndrome:

  • fever > 38C or hypothermia < 36C;
  • heart rate > 90 beats/ minute;
  • respiratory rate > 20 breaths/minute or PaCO2< 32 mmHg or mechanical ventilation for an acute process;
  • WBC count > 12x109/L or < 4x109/L or > 10% immature neutrophils.

Exclusion Criteria:

• Age less than 18 years,
• Pregnant,
• Inability to provide informed, written consent,
• Patients with urologic trauma resulting in frank hematuria, urinary infection, or existing chronic renal disease (serum creatinine level > 2.0 mg/dL),
• Patients receiving nephrotoxic drugs, admitted to the hospital following a surgical procedure, or remaining in the ICU for < 72 hours will be also excluded.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
survivor; survivors of patients
fatalities; non-survivors of patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
mortality	in hospital mortality

Secondary Outcome Measures

Outcome Measure	Time Frame
organ failure	In ICU stay

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: Shu-Min Lin, MD, Chang Gung Memorial Hospital

Publications and helpful links

General Publications

• Lin SM, Wang YM, Lin HC, Lee KY, Huang CD, Liu CY, Wang CH, Kuo HP. Serum thrombomodulin level relates to the clinical course of disseminated intravascular coagulation, multiorgan dysfunction syndrome, and mortality in patients with sepsis. Crit Care Med. 2008 Mar;36(3):683-9. doi: 10.1097/CCM.0B013E31816537D8.

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Anticipated): August 1, 2010
• Study Completion (Anticipated): August 1, 2010

Study Registration Dates

• First Submitted: May 25, 2009
• First Submitted That Met QC Criteria: May 26, 2009
• First Posted (Estimate): May 27, 2009

Study Record Updates

• Last Update Posted (Estimate): May 27, 2009
• Last Update Submitted That Met QC Criteria: May 26, 2009
• Last Verified: May 1, 2009

More Information

Terms related to this study

• Keywords: sepsis; organ failure
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease; Shock; Sepsis; Toxemia; Syndrome; Multiple Organ Failure
• Other Study ID Numbers: 96-1483B