Clinical trial NCT01889823: Effects of Oxygen Status on Hypoxia Inducible Factor 1-α and Inflammation. A Pilot Proof of Principle Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypoxia
Hyperoxia
Keywords: Oxygen
Hypoxia
Hyperoxia
Inflammation
Innate immunity
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2013-06-28
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Hypoxia Inducible Factor 1 alpha in circulating leukocytes
timeFrame: 24 hours
Secondary outcomes:
measure: Hypoxia Inducible Factor mRNA and anti Hypoxia Inducible Factor mRNA in circulating leukocytes
timeFrame: 24 hours
measure: Reactive Oxygen Species in circulating leukocytes
timeFrame: 24 hours
measure: Phagocytic function of circulating leukocytes
timeFrame: 24 hours
measure: cytokine production after ex vivo stimulation of leukocytes
timeFrame: 24 hours
measure: circulating cytokines (including but not limited to IL-6, IL-10, IL-1RA)
timeFrame: 24 hours
measure: Hemodynamic parameters
timeFrame: 24 hours
measure: ventilatory response
timeFrame: 24 hours
measure: adenosine metabolism
timeFrame: 24 hours
measure: alkaline phosphatase
timeFrame: 24 hours
measure: cognitive function
timeFrame: 24 hours
measure: Hepcidin and iron parameters
timeFrame: 24 hours
measure: catecholamines
timeFrame: 24 hours
measure: Neutrophil function
timeFrame: 24 hours
measure: body temperature
timeFrame: 24 hours
measure: oxygen saturation and PaO2
timeFrame: 24 hours
measure: subjective symptoms
timeFrame: 24 hours
measure: high sensitive troponin
timeFrame: 24 hours
measure: iFABP
timeFrame: 24 hours
measure: Brain specific proteins
timeFrame: 24 hours
measure: endocan
timeFrame: 24 hours
measure: adrenomedullin
timeFrame: 24 hours
measure: EPO
timeFrame: 24 hours
measure: VEGF
timeFrame: 24 hours
measure: Heart rate variability
timeFrame: 24 hours
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Intensive Care Medicine, Radboud University Nijmegen Medical Centre
state: Nijmegen, Gelderland
Study officials:
affiliation: Intensive Care Medicine, Radboud University Nijmegen Medical Centre
name: Dorien Kiers, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Intensive Care Medicine, Radboud University Nijmegen Medical Centre
name: Peter Pickkers, MD,PhD
role: STUDY_DIRECTOR
References: