Clinical trial NCT00396344: Cortisol Control of Human Inflammatory Responses to Endotoxin
Official title: The Effect of Glucocorticoid Pre-Treatment on the Systemic Cytokine Response to Endotoxin in Human Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis
Keywords: Systemic sepsis
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2006-11-06
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: The purpose of the research is to study a common and dangerous medical condition called 'septic shock' that often occurs in critically ill patients. In order to learn about septic shock in humans, we will administer a substance called 'endotoxin' to participants in this study. Endotoxin causes a temporary period of inflammation in the human body, a brief 'virtual' infection. This is an established method for the investigation of inflammation properties. We are interested in how the natural hormone, cortisol, can affect the human response to endotoxin. We know that when cortisol is given at the same time as endotoxin it can decrease the inflammation that occurs due to endotoxin. In this study we will test whether or not cortisol, when given the day before the endotoxin, will work to change the inflammation that occurs due to endotoxin. In order to test this, two-thirds of the study participants will receive cortisol on the day before they receive the endotoxin and one-third of the study participants will receive a placebo (no medication) before the endotoxin.


Eligibility criteria: Inclusion Criteria:

* 18 \< age \< 55
* Weight \> 50 kg
* The participant is healthy, without known or suspected medical illness following routine history and physical examination and is expected to easily tolerate the clinical effects of endotoxin.
* The participant does not take any regularly scheduled medication other than thyroid replacement therapy, birth control pills, or estrogenic hormone replacement therapy.

Exclusion Criteria:

* History of chronic disease of any kind such as diabetes, heart disease, cancer, HIV infection, hypertension, asthma, etc.
* History of chronic medication use other than hormone therapy as above
* History of recent acute illness within 30 days prior to study
* Inability to provide informed consent
* History of recent exposure to drugs known to alter immune function including steroids or recent infection (\< 3 months)
* Pregnancy
* History of known risk factors for HIV infection (recent multiple partners, sexually transmitted disease and unprotected sex; intravenous drug use; blood transfusion before 1985)

Primary outcomes:
measure: Plasma cytokine responses to in vivo endotoxin administration
timeFrame: 4 Days
Secondary outcomes:
measure: Plasma acute phase protein response
timeFrame: 4 Days
measure: Clinical response
timeFrame: 8 Hours
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: Mark P Yeager, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yeager MP, Rassias AJ, Pioli PA, Beach ML, Wardwell K, Collins JE, Lee HK, Guyre PM. Pretreatment with stress cortisol enhances the human systemic inflammatory response to bacterial endotoxin. Crit Care Med. 2009 Oct;37(10):2727-32. doi: 10.1097/ccm.0b013e3181a592b3.