Back to resultsEffects of Oxygen Status on Hypoxia Inducible Factor 1-α and Inflammation. A Pilot Proof of Principle Study.
Primary Purpose
Hypoxia, Hyperoxia
Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Hypoxia
Hyperoxia
Sponsored by
About this trial
This is an interventional basic science trial for Hypoxia focused on measuring Oxygen, Hypoxia, Hyperoxia, Inflammation, Innate immunity
Eligibility Criteria
Inclusion Criteria:
- Age ≥18 and ≤35 yrs
- Male
- Healthy
Exclusion Criteria:
- Use of any medication
- Smoking
- History, signs or symptoms of cardiovascular disease
- History of atrial or ventricular arrhythmia
- (Family) history of myocardial infarction or stroke under the age of 65 years
- Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a complex bundle branch block
- Hypertension (defined as RR systolic > 160 or RR diastolic > 90 mmHg)
- Hypotension (defined as RR systolic < 100 or RR diastolic < 50 mmHg)
- Renal impairment (defined as plasma creatinine >120 μmol/l)
- Liver enzyme abnormalities alkaline phosphatase>230 U/L and/or ALT>90 U/L
- Medical history of any obvious disease associated with immune deficiency
- CRP > 20 mg/L, WBC > 12x109/L, or clinically significant acute illness, including infections, within 4 weeks before endotoxemia day
- Participation in a drug trial or donation of blood 3 months prior to the experiment
- Pre-existent lung disease or asthma
- Use of recreational drugs within 21 days prior to experiment day
- Visit to altitude >1500m within 4 weeks prior to the experiment
- Air travel with flight time over 3 hours within 4 weeks prior to the experiment
- History of acute mountain sickness
- Recent hospital admission or surgery with general anaesthesia (<3 months)
- Claustrophobia
- Feelings of discomfort during a 10 minute test wearing the transparent respiratory helmet at the screening visit
Sites / Locations
- Intensive Care Medicine, Radboud University Nijmegen Medical Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Hypoxia
Hyperoxia
Arm Description
Subjects will be breathing an individualized mix of nitrogen and room air titrated to an oxygen saturation of 80-85%.
Subjects will be breathing 100% of oxygen
Outcomes
Primary Outcome Measures
Hypoxia Inducible Factor 1 alpha in circulating leukocytes
Hypoxia Inducible Factor 1 alpha in circulating neutrophils, lymphocytes and monocytes as measured with flow cytometry
Secondary Outcome Measures
Hypoxia Inducible Factor mRNA and anti Hypoxia Inducible Factor mRNA in circulating leukocytes
Reactive Oxygen Species in circulating leukocytes
ROS in circulating leukocytes, subclassified in neutrophils and monocytes
Phagocytic function of circulating leukocytes
cytokine production after ex vivo stimulation of leukocytes
circulating cytokines (including but not limited to IL-6, IL-10, IL-1RA)
Hemodynamic parameters
Blood pressure, heart frequency, cardiac output measurement
ventilatory response
Measures of ventilation: respiratory rate, blood gas changes
adenosine metabolism
urine and plasma adenosine,adenosine receptor mRNA, purines
alkaline phosphatase
cognitive function
neuropsychologic assessment of cognitive function
Hepcidin and iron parameters
catecholamines
adrenaline, noradrenaline and dopamine
Neutrophil function
body temperature
oxygen saturation and PaO2
subjective symptoms
high sensitive troponin
iFABP
Brain specific proteins
endocan
adrenomedullin
EPO
VEGF
Heart rate variability
Full Information
NCT ID
NCT01889823
First Posted
June 26, 2013
Last Updated
March 24, 2015
Sponsor
Radboud University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT01889823
Brief Title
Effects of Oxygen Status on Hypoxia Inducible Factor 1-α and Inflammation. A Pilot Proof of Principle Study.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
June 2013 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Radboud University Medical Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
It has been shown in in vitro and animal models that hypoxia can have pro-inflammatory effects and hyperoxia can have anti-inflammatory effects. The pro-inflammatory effect could be the result of activation of Hypoxia Inducible Factor, a transcription factor that is known to activate many cell systems aimed at cell survival, including the inflammatory response. The anti-inflammatory effects of hyperoxia could be the annihilation of Hypoxia Inducible Factor, but also a decrease in inflammation due to oxygen toxicity resulting in a decrease in clearance of pathogens. These effects have been sparsely studied in humans. Therefore, we hypothesize that hypoxia results in an increase in Hypoxia Inducible Factor in circulating leukocytes and increases inflammatory reactions, whereas hyperoxia decreases these reactions.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoxia, Hyperoxia
Keywords
Oxygen, Hypoxia, Hyperoxia, Inflammation, Innate immunity
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Hypoxia
Arm Type
Experimental
Arm Description
Subjects will be breathing an individualized mix of nitrogen and room air titrated to an oxygen saturation of 80-85%.
Arm Title
Hyperoxia
Arm Type
Experimental
Arm Description
Subjects will be breathing 100% of oxygen
Intervention Type
Other
Intervention Name(s)
Hypoxia
Intervention Description
Subjects will be breathing an individualized mix of nitrogen and room air titrated to an oxygen saturation of 80-85%.
Intervention Type
Other
Intervention Name(s)
Hyperoxia
Intervention Description
Subjects will be breathing 100% oxygen
Primary Outcome Measure Information:
Title
Hypoxia Inducible Factor 1 alpha in circulating leukocytes
Description
Hypoxia Inducible Factor 1 alpha in circulating neutrophils, lymphocytes and monocytes as measured with flow cytometry
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Hypoxia Inducible Factor mRNA and anti Hypoxia Inducible Factor mRNA in circulating leukocytes
Time Frame
24 hours
Title
Reactive Oxygen Species in circulating leukocytes
Description
ROS in circulating leukocytes, subclassified in neutrophils and monocytes
Time Frame
24 hours
Title
Phagocytic function of circulating leukocytes
Time Frame
24 hours
Title
cytokine production after ex vivo stimulation of leukocytes
Time Frame
24 hours
Title
circulating cytokines (including but not limited to IL-6, IL-10, IL-1RA)
Time Frame
24 hours
Title
Hemodynamic parameters
Description
Blood pressure, heart frequency, cardiac output measurement
Time Frame
24 hours
Title
ventilatory response
Description
Measures of ventilation: respiratory rate, blood gas changes
Time Frame
24 hours
Title
adenosine metabolism
Description
urine and plasma adenosine,adenosine receptor mRNA, purines
Time Frame
24 hours
Title
alkaline phosphatase
Time Frame
24 hours
Title
cognitive function
Description
neuropsychologic assessment of cognitive function
Time Frame
24 hours
Title
Hepcidin and iron parameters
Time Frame
24 hours
Title
catecholamines
Description
adrenaline, noradrenaline and dopamine
Time Frame
24 hours
Title
Neutrophil function
Time Frame
24 hours
Title
body temperature
Time Frame
24 hours
Title
oxygen saturation and PaO2
Time Frame
24 hours
Title
subjective symptoms
Time Frame
24 hours
Title
high sensitive troponin
Time Frame
24 hours
Title
iFABP
Time Frame
24 hours
Title
Brain specific proteins
Time Frame
24 hours
Title
endocan
Time Frame
24 hours
Title
adrenomedullin
Time Frame
24 hours
Title
EPO
Time Frame
24 hours
Title
VEGF
Time Frame
24 hours
Title
Heart rate variability
Time Frame
24 hours
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Age ≥18 and ≤35 yrs
Male
Healthy
Exclusion Criteria:
Use of any medication
Smoking
History, signs or symptoms of cardiovascular disease
History of atrial or ventricular arrhythmia
(Family) history of myocardial infarction or stroke under the age of 65 years
Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a complex bundle branch block
Hypertension (defined as RR systolic > 160 or RR diastolic > 90 mmHg)
Hypotension (defined as RR systolic < 100 or RR diastolic < 50 mmHg)
Renal impairment (defined as plasma creatinine >120 μmol/l)
Liver enzyme abnormalities alkaline phosphatase>230 U/L and/or ALT>90 U/L
Medical history of any obvious disease associated with immune deficiency
CRP > 20 mg/L, WBC > 12x109/L, or clinically significant acute illness, including infections, within 4 weeks before endotoxemia day
Participation in a drug trial or donation of blood 3 months prior to the experiment
Pre-existent lung disease or asthma
Use of recreational drugs within 21 days prior to experiment day
Visit to altitude >1500m within 4 weeks prior to the experiment
Air travel with flight time over 3 hours within 4 weeks prior to the experiment
History of acute mountain sickness
Recent hospital admission or surgery with general anaesthesia (<3 months)
Claustrophobia
Feelings of discomfort during a 10 minute test wearing the transparent respiratory helmet at the screening visit
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dorien Kiers, MD
Organizational Affiliation
Intensive Care Medicine, Radboud University Nijmegen Medical Centre
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Peter Pickkers, MD,PhD
Organizational Affiliation
Intensive Care Medicine, Radboud University Nijmegen Medical Centre
Official's Role
Study Director
Facility Information:
Facility Name
Intensive Care Medicine, Radboud University Nijmegen Medical Centre
City
Nijmegen
State/Province
Nijmegen, Gelderland
ZIP/Postal Code
6500 HB
Country
Netherlands
12. IPD Sharing Statement
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Effects of Oxygen Status on Hypoxia Inducible Factor 1-α and Inflammation. A Pilot Proof of Principle Study.
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