Clinical trial NCT00185783: Impact of Hydrocortisone Administration on White Blood Cell Gene Expression in Patients With Severe Sepsis
Official title: Pilot Study of White Blood Cell Gene Expression in Critically Ill Patients With Severe Sepsis and Relative Adrenal Insufficiency After Hydrocortisone Administration
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sepsis
Relative Adrenal Insufficiency
Keywords: Sepsis
Adrenal Insufficiency
Hydrocortisone
Gene Expression
Microarray
RNA
Critically Ill
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: University of Toronto
name: University of Colorado, Denver
First posted: 2005-09-16
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients admitted to the Stanford Hospital ICU with Sepsis.

Brief summary: The purpose of this pilot study is to (1) examine the changes in gene expression in patients who suffer from severe sepsis and whose shock (inadequate oxygen delivery to vital organs) state does not respond to fluid and vasopressor administration, (2) to show that our sampling method of isolating RNA provides reliable and consistent data, (3) provide a basis for future gene expression studies in critically ill patients

Detailed description: Severe sepsis is characterized by inadequate perfusion of vital organs due to infection. More than 750,000 cases of severe sepsis occur each year in the United States. Mortality among patients with severe sepsis ranges from 7% to 50%. Initiation of antibiotic therapy within the first hour of diagnosis as well as fluid resuscitation and hemodynamic stabilization are primary goals of therapy.

Steroid administration has been shown to improve outcome in the subset of severe sepsis patients suffering from relative adrenal insufficiency. Although initial studies using high dose short course steroid therapy did not demonstrate efficacy, more recent studies of low dose longer duration hydrocortisone administration demonstrated a significant reduction in mortality at 28 days. The mechanism by which steroid administration affords protection is unclear. We hypothesize that steroid administration changes white blood cell gene and protein expression in severe sepsis patients from an immuno-inflammatory profile to a pattern consistent with healing.

Our first specific aim is to obtain plasma and total cellular RNA from leukocytes in the blood of ten patients admitted to Stanford Medical Center with the diagnosis of severe sepsis and adrenal insufficiency. Significant and distinct variations in whole blood leukocyte gene expression patterns occur depending upon the method of RNA isolation. We will attempt to demonstrate that our sampling method provides reliable and consistent data.

Our second specific aim is to begin an analysis of gene expression patterns in white blood cells before and after steroid administration in patients suffering from severe sepsis with relative adrenal insufficiency. We will use a protocol for assessment of gene expression that was developed by members of our research team.

Eligibility criteria: Inclusion Criteria:

* Admission Diagnosis of Sepsis
* Evidence of Relative Adrenal Insufficiency
* Hypotension (Mean Arterial Pressure less than 60 mm Hg) Refractory to a. Fluid Resuscitation b. Dopamine infusion (greater than 5 micrograms/kg/min) c. Phenylephrine infusion (greater than 1 microgram/kg/min)

Exclusion Criteria:

* Use of Immunosuppressant Medications
* Immune Compromised Due to Disease (e.g., HIV infection)
* Transfusion of Blood Products within the past 7 Days
* Use of Cytokine Therapy (i.e., G-CSF)
* History of Bone Marrow Transplantation

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
Study officials:
affiliation: Stanford University, Dept. of Anesthesia, Division of Critical Care Medicine
name: Andrew J Patterson, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University, Dept. of Medicine, Div. of Pulmonary and Critical Care Medicine
name: Ann Weinacker, M.D.,
role: PRINCIPAL_INVESTIGATOR
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citation: Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med. 2004 Apr;30(4):536-55. doi: 10.1007/s00134-004-2210-z. Epub 2004 Mar 3.
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