Impact of Hydrocortisone Administration on White Blood Cell Gene Expression in Patients With Severe Sepsis

NCT ID: NCT00185783

Last Updated: 2011-04-11

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 10 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2005-03-31
• Study Completion Date: 2006-11-30

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.

Conditions

Sepsis; Relative Adrenal Insufficiency

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Hydrocortisone Administration (Standard of Care Therapy)

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Toronto

OTHER

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Stanford University

Principal Investigators

Andrew J Patterson, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Stanford University, Dept. of Anesthesia, Division of Critical Care Medicine

Ann Weinacker, M.D.,

Role: PRINCIPAL_INVESTIGATOR

Stanford University, Dept. of Medicine, Div. of Pulmonary and Critical Care Medicine

Locations

Stanford University Medical Center

Stanford, California, United States

Countries

United States

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 12186604 (View on PubMed)

Other Identifiers

Stanford IRB Number 4593

Identifier Type: -

Identifier Source: secondary_id

Other Grant

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

95230

Identifier Type: -

Identifier Source: org_study_id