SepsisNCT00185783
Impact of Hydrocortisone Administration on White Blood Cell Gene Expression in Patients With Severe Sepsis
An observational study of Sepsis and Relative Adrenal Insufficiency, run by Stanford University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Relative Adrenal Insufficiency
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2005to Nov 2006
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients admitted to the Stanford Hospital ICU with Sepsis.
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University Medical Center
Stanford, California, 94305
About this study
Official title: Pilot Study of White Blood Cell Gene Expression in Critically Ill Patients With Severe Sepsis and Relative Adrenal Insufficiency After Hydrocortisone Administration
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
Read the 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
- Being tested
- Hydrocortisone Administration (Standard of Care Therapy)
- Keywords
- Sepsis, Adrenal Insufficiency, Hydrocortisone, Gene Expression, Microarray, RNA, Critically Ill
- Medical subject headings
- Sepsis, Adrenal Insufficiency, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydrocortisone Administration (Standard of Care Therapy)Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startMar 2005
- Primary completionNov 2006
- Study completionNov 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Toronto, University of Colorado, Denver
- Investigators
- Andrew J Patterson, M.D., Ph.D., Principal investigator, Stanford University, Dept. of Anesthesia, Division of Critical Care MedicineAnn Weinacker, M.D.,, Principal investigator, Stanford University, Dept. of Medicine, Div. of Pulmonary and Critical Care Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00185783
- Sponsor's protocol ID
- 95230
- Other IDs
- Stanford IRB Number 4593, Other Grant
- Status last verified
- Apr 2011
- First submitted
- 12 Sep 2005
- Last updated
- 11 Apr 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Spiegelman JI, Mindrinos MN, Oefner PJ. High-accuracy DNA sequence variation screening by DHPLC. Biotechniques. 2000 Nov;29(5):1084-90, 1092. doi: 10.2144/00295rr04.
PubMed 11084871Steinmetz LM, Mindrinos M, Oefner PJ. Combining genome sequences and new technologies for dissecting the genetics of complex phenotypes. Trends Plant Sci. 2000 Sep;5(9):397-401. doi: 10.1016/s1360-1385(00)01724-6. No abstract available.
PubMed 10973096Wang QT, Piotrowska K, Ciemerych MA, Milenkovic L, Scott MP, Davis RW, Zernicka-Goetz M. A genome-wide study of gene activity reveals developmental signaling pathways in the preimplantation mouse embryo. Dev Cell. 2004 Jan;6(1):133-44. doi: 10.1016/s1534-5807(03)00404-0.
PubMed 14723853Dellinger 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 Management Guidelines Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004 Mar;32(3):858-73. doi: 10.1097/01.ccm.0000117317.18092.e4.
PubMed 15090974Dellinger 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.
PubMed 14997291Dellinger RP. Cardiovascular management of septic shock. Crit Care Med. 2003 Mar;31(3):946-55. doi: 10.1097/01.CCM.0000057403.73299.A6. No abstract available.
PubMed 12627010Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaud P, Bellissant E. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002 Aug 21;288(7):862-71. doi: 10.1001/jama.288.7.862.
PubMed 12186604
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of White Blood Cell Gene Expression in Critically Ill Patients With Severe Sepsis and Relative Adrenal Insufficiency After Hydrocortisone Administration
- ClinicalTrials.gov ID
- NCT00185783
- Acronym / sponsor ID
- 95230
- Conditions
- Sepsis, Relative Adrenal Insufficiency
- Keywords
- Sepsis, Adrenal Insufficiency, Hydrocortisone, Gene Expression, Microarray, RNA, Critically Ill
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- University of Toronto, University of Colorado, Denver
- Study start
- Mar 2005
- Primary completion
- Nov 2006 (actual)
- Study completion
- Nov 2006 (actual)
- First posted
- 16 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients admitted to the Stanford Hospital ICU with Sepsis.
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydrocortisone Administration (Standard of Care Therapy) | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2011.
- Background: PubMed 11084871Spiegelman JI, Mindrinos MN, Oefner PJ. High-accuracy DNA sequence variation screening by DHPLC. Biotechniques. 2000 Nov;29(5):1084-90, 1092. doi: 10.2144/00295rr04.
- Background: PubMed 10973096Steinmetz LM, Mindrinos M, Oefner PJ. Combining genome sequences and new technologies for dissecting the genetics of complex phenotypes. Trends Plant Sci. 2000 Sep;5(9):397-401. doi: 10.1016/s1360-1385(00)01724-6. No abstract available.
- Background: PubMed 14723853Wang QT, Piotrowska K, Ciemerych MA, Milenkovic L, Scott MP, Davis RW, Zernicka-Goetz M. A genome-wide study of gene activity reveals developmental signaling pathways in the preimplantation mouse embryo. Dev Cell. 2004 Jan;6(1):133-44. doi: 10.1016/s1534-5807(03)00404-0.
- Background: PubMed 15090974Dellinger 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 Management Guidelines Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004 Mar;32(3):858-73. doi: 10.1097/01.ccm.0000117317.18092.e4.
- Background: PubMed 14997291Dellinger 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.
- Background: PubMed 12627010Dellinger RP. Cardiovascular management of septic shock. Crit Care Med. 2003 Mar;31(3):946-55. doi: 10.1097/01.CCM.0000057403.73299.A6. No abstract available.
- Background: PubMed 12186604Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaud P, Bellissant E. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002 Aug 21;288(7):862-71. doi: 10.1001/jama.288.7.862.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew J Patterson, M.D., Ph.D. principal investigator
Stanford University, Dept. of Anesthesia, Division of Critical Care Medicine
Ann Weinacker, M.D., principal investigator
Stanford University, Dept. of Medicine, Div. of Pulmonary and Critical Care Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis and Relative Adrenal Insufficiency, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Apr 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00185783, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2011.