Evaluation of Intestinal Brush Border Enzyme Function in Critically Ill Patients - Full Text View

Purpose

The purpose of this study is to evaluate the role of several enzymes of the gut mucosa in preventing invasion of gastrointestinal bacteria.

Condition	Intervention
Critical Illness Septic Shock SIRS	Procedure: Gastroscopy

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	Evaluation of Intestinal Brush Border Enzyme Function in Patients With SIRS and Septic Shock Compared to Control Patients

Resource links provided by NLM:

MedlinePlus related topics: Shock

U.S. FDA Resources

Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:

activity of the brush border membrane enzyme intestinal alkaline phosphatase [ Time Frame: at inclusion ] [ Designated as safety issue: No ]
Duodenal biopsies will be taken on day 0 (at inclusion) and will be subsequently frozen. Determination of enzyme activity will be done within 28 days.

Secondary Outcome Measures:

activity of the brush border membrane enzyme maltase [ Time Frame: at inclusion ] [ Designated as safety issue: No ]
Duodenal biopsies will be taken on day 0 (at inclusion) and will be subsequently frozen. Determination of enzyme activity will be done within 28 days.
activity of the brush border membrane enzyme lactase [ Time Frame: at inclusion ] [ Designated as safety issue: No ]
Duodenal biopsies will be taken on day 0 (at inclusion) and will be subsequently frozen. Determination of enzyme activity will be done within 28 days.
Brush border morphology [ Time Frame: at inclusion ] [ Designated as safety issue: No ]
Duodenal biopsies will be taken on day 0 (at inclusion) and will be subsequently frozen. Determination of enzyme activity will be done within 28 days.
ICU mortality [ Time Frame: at ICU discharge ] [ Designated as safety issue: No ]
only for groups "septic shock" and "SIRS"
hospital mortality [ Time Frame: at hospital discharge ] [ Designated as safety issue: No ]
only for groups "septic shock" and "SIRS"
mortality (6 months) [ Time Frame: 6 months after inclusion ] [ Designated as safety issue: No ]

Estimated Enrollment:	45
Study Start Date:	July 2011
Estimated Study Completion Date:	April 2013
Estimated Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Septic Shock Activity of the brush border membrane enzymes intestinal alkaline phosphatase, maltase and lactase, as well as brush border morphology determined from duodenal biopsies in patients with septic shock	Procedure: Gastroscopy When gastroscopy is indicated for clinical reasons, duodenal biopsies to determine the activity of the brush border membrane enzymes intestinal alkaline phosphatase, maltase and lactase, as well as assessing brush border morphology are taken
SIRS Activity of the brush border membrane enzymes intestinal alkaline phosphatase, maltase and lactase, as well as brush border morphology determined from duodenal biopsies in patients with SIRS	Procedure: Gastroscopy When gastroscopy is indicated for clinical reasons, duodenal biopsies to determine the activity of the brush border membrane enzymes intestinal alkaline phosphatase, maltase and lactase, as well as assessing brush border morphology are taken
healthy/controls Activity of the brush border membrane enzymes intestinal alkaline phosphatase, maltase and lactase, as well as brush border morphology determined from duodenal biopsies in patients without SIRS/septic shock	Procedure: Gastroscopy When gastroscopy is indicated for clinical reasons, duodenal biopsies to determine the activity of the brush border membrane enzymes intestinal alkaline phosphatase, maltase and lactase, as well as assessing brush border morphology are taken

Detailed Description:

Systemic Inflammatory Response Syndrome (SIRS), sepsis, septic shock and concomitant multiorgan failure are major causes of morbidity and mortality in intensive care units. During SIRS and septic shock the role of the gut seems to be uncertain. As it serves as an intestinal barrier which allows the symbiotic relationship between man and enteric bacteria, increased gut permeability during critical illness is accused to promote sepsis. Brush border enzymes have the ability to detoxify lipopolysaccharides and prevent bacterial invasion across the gut mucosal barrier. A reduced brush border enzyme function could contribute to the gastrointestinal intolerance in critically ill patients, which is frequently observed. The aim of this study is to assess the influence of SIRS and septic shock on brush border enzyme morphology and function in men.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Septic Shock:

Recruitment and inclusion criteria

15 mechanically ventilated critically ill patients fulfilling criteria of SIRS (2 symptoms: RR > 20/min, HR > 90/min, Temp. > 38°/< 36°, 12G/l< WBC < 4G/l; assumed or proven infection, persistent hypotension refractory to fluid therapy and need for vasopressors.
Time window for inclusion: up to 72h after onset of symptoms

Exclusion criteria

PLT < 50G/l,
PT < 50%,
Continuous therapeutic anticoagulation,
DIC, st. p. MCI within 14 days,
Gastrointestinal perforation,
Age < 18 years,
Age > 80 Years

SIRS:

Recruitment and inclusion criteria

15 mechanically ventilated critically ill patients fulfilling criteria of SIRS (2 symptoms: RR > 20/min, HR > 90/min, Temp. > 38°/< 36°, 12G/l < WBC < 4G/l; assumed or proven infection
Time window for inclusion: up to 72h after onset of symptoms

Exclusion criteria:

PLT < 50G/l,
PT < 50%, continuous therapeutic anticoagulation,
DIC, st. p. MCI within 14 days,
Gastrointestinal perforation,
Age < 18 years,
Age > 80 Years

Healthy/controls:

15 control subjects will be recruited from the outpatient ward referred to the endoscopy of the Department of Medicine III - Division of Gastroenterology and Hepatology for upper GI-endoscopy because of epigastric pain or reflux symptoms.

Inclusion criteria:

Signed informed consent

Exclusion criteria:

Patients with diarrhea of unknown origin, IBD or known celiac disease
Age < 18 years
Age > 80 Years
PLT < 50G/l, PT < 50%
Therapeutic oral anticoagulation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01585909

Contacts

Contact: Ulrike Holzinger, MD	0043 1 40400 ext 4767	ulrike.holzinger@meduniwien.ac.at
Contact: Richard Brunner, MD	0043 1 40400 ext 4766	richard.brunner@meduniwien.ac.at

Locations

Austria
Medical University Vienna	Recruiting
Vienna, Austria, 1090
Contact: Ulrike Holzinger, MD 0043 1 40400 ext 4767 ulrike.holzinger@meduniwien.ac.at
Principal Investigator: Ulrike Holzinger, MD

Sponsors and Collaborators

Medical University of Vienna

Investigators

Principal Investigator:

Ulrike Holzinger, MD

Medical University of Vienna

More Information

No publications provided

Responsible Party:	Ulrike Holzinger, MD, Assoc Prof, Medical University of Vienna
ClinicalTrials.gov Identifier:	NCT01585909 History of Changes
Other Study ID Numbers:	BBM_septic_shock
Study First Received:	April 12, 2012
Last Updated:	April 24, 2012
Health Authority:	Austria: Ethikkommission

Additional relevant MeSH terms:

Critical Illness
Shock
Shock, Septic
Disease Attributes
Pathologic Processes

Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation

ClinicalTrials.gov processed this record on May 16, 2013