Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Collaborators:
University of Toronto
University of Colorado, Denver
Information provided by:
Stanford University
ClinicalTrials.gov Identifier:
NCT00185783
First received: September 12, 2005
Last updated: April 7, 2011
Last verified: April 2011
  Purpose

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


Condition Intervention Phase
Sepsis
Relative Adrenal Insufficiency
Drug: Hydrocortisone Administration (Standard of Care Therapy)
Phase 1

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pilot Study of White Blood Cell Gene Expression in Critically Ill Patients With Severe Sepsis and Relative Adrenal Insufficiency After Hydrocortisone Administration

Resource links provided by NLM:


Further study details as provided by Stanford University:

Enrollment: 10
Study Start Date: March 2005
Study Completion Date: November 2006
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients admitted to the Stanford Hospital ICU with Sepsis.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00185783

Locations
United States, California
Stanford University Medical Center
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
University of Toronto
University of Colorado, Denver
Investigators
Principal Investigator: Andrew J Patterson, M.D., Ph.D. Stanford University, Dept. of Anesthesia, Division of Critical Care Medicine
Principal Investigator: Ann Weinacker, M.D., Stanford University, Dept. of Medicine, Div. of Pulmonary and Critical Care Medicine
  More Information

Publications:

Responsible Party: Andrew J. Patterson, M.D., Ph.D., Stanford University
ClinicalTrials.gov Identifier: NCT00185783     History of Changes
Other Study ID Numbers: 95230, Stanford IRB Number 4593, Other Grant
Study First Received: September 12, 2005
Last Updated: April 7, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Stanford University:
Sepsis
Adrenal Insufficiency
Hydrocortisone
Gene Expression
Microarray
RNA
Critically Ill

Additional relevant MeSH terms:
Adrenal Insufficiency
Sepsis
Toxemia
Adrenal Gland Diseases
Endocrine System Diseases
Infection
Inflammation
Pathologic Processes
Systemic Inflammatory Response Syndrome
Cortisol succinate
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone-17-butyrate
Anti-Inflammatory Agents
Dermatologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014