Ignite Creation Date:
2025-12-25 @ 12:00 AM
Ignite Modification Date:
2026-01-25 @ 8:49 AM
Study NCT ID:
NCT01978158
Status:
COMPLETED
Last Update Posted:
2015-05-20
First Post:
2013-10-31
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Effects of Oxygen Status on Endotoxemia Induced Inflammation and Hypoxia Inducible Factor-1α
Sponsor:
Radboud University Medical Center
Organization:
Study Overview
Official Title:
Effects of Oxygen Status on Endotoxemia Induced Inflammation and Hypoxia Inducible Factor-1α. A Pilot Proof of Principle Study
Status:
COMPLETED
Status Verified Date:
2015-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Oxygen is a widely available gas that is cheap, easy to get and extensively used in medicine. From animal studies it has become apparent that increasing or lowering the degree of oxygen in the blood, the inflammatory response can be altered. We will investigate of this is also true in humans by increasing, lowering or keeping oxygen levels normal while giving healthy subjects a short inflammatory stimulus.
Detailed Description:
The primary objective of the study is to determine the effects of hyperoxia and hypoxia compared to normoxia in the human endotoxemia model on the innate immune reponse in healthy volunteers.
A parallel, randomized study in healthy male volunteers. The subjects will be randomized to hypoxia, hyperoxia, or normoxia, and will all undergo experimental human endotoxemia (administration of 2 ng/kg LPS iv).
In the hypoxia group: the subjects will breathe an individualized mix of nitrogen and room air for 3.5 hours using an air-tight respiratory helmet. The gas mixture will be adjusted to achieve a saturation of 80-85%. In the hyperoxia group, subjects will breathe 100% oxygen for 3.5 hours using the same respiratory helmet. In the normoxia group, subjects will breathe room air (21% oxygen, 79% nitrogen) also wearing the respiratory helmet. 1 hour after oxygen status adjustment (t=0), all subject will be administered an intravenous bolus (2ng/kg) of LPS derived from E coli O:113. 2.5 hours after LPS administration, the helmets will be removed and all subjects will breathe ambient room air.
The primary study endpoint is the difference in plasma cytokines between the hypoxia and normoxia group, and between the hyperoxia and normoxia group. Secondary objectives include HIF-1α protein and mRNA, aHIF mRNA expression in circulating leukocytes, measures of ROS, leukocyte phagocytosis, and cytokine production by leukocytes stimulated ex vivo with various inflammatory stimuli, and measurement of basic hemodynamic and ventilatory parameters and temperature.
A parallel, randomized study in healthy male volunteers. The subjects will be randomized to hypoxia, hyperoxia, or normoxia, and will all undergo experimental human endotoxemia (administration of 2 ng/kg LPS iv).
In the hypoxia group: the subjects will breathe an individualized mix of nitrogen and room air for 3.5 hours using an air-tight respiratory helmet. The gas mixture will be adjusted to achieve a saturation of 80-85%. In the hyperoxia group, subjects will breathe 100% oxygen for 3.5 hours using the same respiratory helmet. In the normoxia group, subjects will breathe room air (21% oxygen, 79% nitrogen) also wearing the respiratory helmet. 1 hour after oxygen status adjustment (t=0), all subject will be administered an intravenous bolus (2ng/kg) of LPS derived from E coli O:113. 2.5 hours after LPS administration, the helmets will be removed and all subjects will breathe ambient room air.
The primary study endpoint is the difference in plasma cytokines between the hypoxia and normoxia group, and between the hyperoxia and normoxia group. Secondary objectives include HIF-1α protein and mRNA, aHIF mRNA expression in circulating leukocytes, measures of ROS, leukocyte phagocytosis, and cytokine production by leukocytes stimulated ex vivo with various inflammatory stimuli, and measurement of basic hemodynamic and ventilatory parameters and temperature.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: