Cortisol Control of Human Inflammatory Responses to Endotoxin

Study Overview
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Brief Summary
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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.

Official Title
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The Effect of Glucocorticoid Pre-Treatment on the Systemic Cytokine Response to Endotoxin in Human Volunteers

Conditions
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Sepsis

Intervention / Treatment
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* Other: Çontrol
* Drug: Hydrocortisone
* Drug: Hydrocortisone


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Saline control | Other: Çontrol<br>* Intravenous saline<br>|
| Experimental: 2<br> | Drug: Hydrocortisone<br>* Intravenous stress dose of hydrocortisone<br>|
| Experimental: 3<br> | Drug: Hydrocortisone<br>* Intravenous pharmacologic hydrocortisone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma cytokine responses to in vivo endotoxin administration |  | 4 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma acute phase protein response |  | 4 Days | 
| Clinical response |  | 8 Hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic sepsis