Impact of Hydrocortisone Administration on White Blood Cell Gene Expression in Patients With Severe Sepsis
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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 |
| 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) |
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 |
Patients admitted to the Stanford Hospital ICU with Sepsis.
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| United States, California | |
| Stanford University Medical Center | |
| Stanford, California, United States, 94305 | |
| 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 Addison Disease Critical Illness Sepsis Toxemia Adrenal Gland Diseases Endocrine System Diseases Autoimmune Diseases Immune System Diseases Disease Attributes Pathologic Processes Infection |
Systemic Inflammatory Response Syndrome Inflammation Cortisol succinate Hydrocortisone acetate Hydrocortisone 17-butyrate 21-propionate Hydrocortisone Hydrocortisone-17-butyrate Anti-Inflammatory Agents Therapeutic Uses Pharmacologic Actions Dermatologic Agents |
ClinicalTrials.gov processed this record on May 19, 2013