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

Sepsis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00908635
• Other study ID #: 96-1483B
• Status: Recruiting
• Phase: N/A
• First received: May 25, 2009
• Last updated: May 26, 2009
• Start date: July 2008
• Est. completion date: August 2010

Study information

• Verified date: May 2009
• Source: Chang Gung Memorial Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

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 Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Multiple Organ Dysfunction Syndrome
• Multiple Organ Failure
• Sepsis
• Syndrome
• Toxemia

Locations

Country	Name	City	State
Taiwan	Chang Gung Memorial Hospital	Taoyuan

Sponsors (1)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	mortality		in hospital mortality	No
Secondary	organ failure		In ICU stay	No