Effects of Oxygen Status on Hypoxia Inducible Factor 1-α and Inflammation. A Pilot Proof of Principle Study.

Radboud University Medical Center

Status and phase

Completed

Phase 1

Conditions

Hyperoxia

Hypoxia

Treatments

Other: Hyperoxia

Other: Hypoxia

Study type

Interventional

Funder types

Other

Identifiers

NCT01889823

OX1

Details and patient eligibility

About

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.

Enrollment

20 patients

Sex

Male

Ages

18 to 35 years old

Volunteers

Accepts Healthy Volunteers

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