Skip to main content
OpenTrials
Completed

NCT Number: NCT01889823

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Age range

18 year–35 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Intensive Care Medicine, Radboud University Nijmegen Medical Centre

Nijmegen, Nijmegen, Gelderland, 6500 HB, Netherlands

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Hypoxia

Other

Subjects will be breathing an individualized mix of nitrogen and room air titrated to an oxygen saturation of 80-85%.

Hyperoxia

Other

Subjects will be breathing 100% oxygen

Primary outcomes

  1. Hypoxia Inducible Factor 1 alpha in circulating leukocytes

    Time frame: 24 hours

    Hypoxia Inducible Factor 1 alpha in circulating neutrophils, lymphocytes and monocytes as measured with flow cytometry

Secondary outcomes

  1. Hypoxia Inducible Factor mRNA and anti Hypoxia Inducible Factor mRNA in circulating leukocytes

    Time frame: 24 hours

  2. Reactive Oxygen Species in circulating leukocytes

    Time frame: 24 hours

    ROS in circulating leukocytes, subclassified in neutrophils and monocytes

  3. Phagocytic function of circulating leukocytes

    Time frame: 24 hours

  4. cytokine production after ex vivo stimulation of leukocytes

    Time frame: 24 hours

  5. circulating cytokines (including but not limited to IL-6, IL-10, IL-1RA)

    Time frame: 24 hours

  6. Hemodynamic parameters

    Time frame: 24 hours

    Blood pressure, heart frequency, cardiac output measurement

  7. ventilatory response

    Time frame: 24 hours

    Measures of ventilation: respiratory rate, blood gas changes

  8. adenosine metabolism

    Time frame: 24 hours

    urine and plasma adenosine,adenosine receptor mRNA, purines

  9. alkaline phosphatase

    Time frame: 24 hours

  10. cognitive function

    Time frame: 24 hours

    neuropsychologic assessment of cognitive function

  11. Hepcidin and iron parameters

    Time frame: 24 hours

  12. catecholamines

    Time frame: 24 hours

    adrenaline, noradrenaline and dopamine

  13. Neutrophil function

    Time frame: 24 hours

  14. body temperature

    Time frame: 24 hours

  15. oxygen saturation and PaO2

    Time frame: 24 hours

  16. subjective symptoms

    Time frame: 24 hours

  17. high sensitive troponin

    Time frame: 24 hours

  18. iFABP

    Time frame: 24 hours

  19. Brain specific proteins

    Time frame: 24 hours

  20. endocan

    Time frame: 24 hours

  21. adrenomedullin

    Time frame: 24 hours

  22. EPO

    Time frame: 24 hours

  23. VEGF

    Time frame: 24 hours

  24. Heart rate variability

    Time frame: 24 hours

Sponsors and collaborators

Lead sponsor

Radboud University Medical Center

Other

Registry information

Important dates

Study start
2013
Primary completion
2013
Study completion
2014
First posted
Jun 28, 2013
Registry last updated
Mar 25, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.