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HypoxiaPhase 1/2NCT01978158

Effects of Oxygen Status on Endotoxemia Induced Inflammation and Hypoxia Inducible Factor-1α

A Phase 1/2 study testing Lipopolysaccharide in people with Hypoxia and Normoxia, run by Radboud University Medical Center at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 35 years, men onlyHealthy volunteers can take part
Conditions the study is for
Hypoxia, Normoxia, Hyperoxia
What is being tested?
Lipopolysaccharide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteNetherlands
Study dates
Oct 2013to Dec 2013
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 35 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Written informed consent to participate in this trial
  • Male subjects aged 18 to 35 years inclusive
  • Healthy as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram, and clinical laboratory parameters

Who cannot join

  • Use of any medication(including herbal remedies and vitamin/mineral supplements) or recreational drugs within 7 days prior to profiling day
  • Smoking
  • Use of caffeine, or alcohol or within 1 day prior to profiling day
  • Previous participation in a trial where LPS was administered
  • Surgery or trauma with significant blood loss or blood donation within 3 months prior to profiling day
  • Participation in another clinical trial within 3 months prior to profiling day.
Show all 23Show fewer
  • History, signs or symptoms of cardiovascular disease
  • An implant that in the opinion of the investigator may make invasive procedures risky for the subject due to the increased risks associated with a possible infection.
  • Subject has an implanted active cardiac device (ICD, IPG and/or CRT) Implanted active neurostimulation device
  • Subject has internal jugular vein that cannot be accessed
  • History of vaso-vagal collapse or of orthostatic hypotension
  • History of atrial or ventricular arrhythmia
  • Resting pulse rate ≤45 or ≥100 beats / min
  • Hypertension (RR systolic >160 or RR diastolic >90)
  • Hypotension (RR systolic <100 or RR diastolic <50)
  • Conduction abnormalities on the ECG consisting of a 1st degree atrioventricular block or a complex bundle branch block
  • Subject is diagnosed with epilepsy or history of seizures
  • Renal impairment: plasma creatinine >120 μmol/L
  • Liver function abnormality: alkaline phosphatase>230 U/L and/or ALT>90 U/L
  • Coagulation abnormalities: APTT or PT > 1.5 times the reference range
  • History of asthma
  • Immuno-deficiency CRP > 20 mg/L, WBC > 12x109/L, or clinically significant acute illness, including infections, within 2 weeks before profiling day
  • Known or suspected of not being able to comply with the trial protocol - Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Intensive Care Medicine

    Nijmegen, Gelderland, 6500HB

Other trials in Netherlands

About this study

Official title: Effects of Oxygen Status on Endotoxemia Induced Inflammation and Hypoxia Inducible Factor-1α. A Pilot Proof of Principle Study

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.

Read the 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.

Being tested
Lipopolysaccharide
Keywords
Oxygen, Hypoxia, Hyperoxia, Inflammation, Innate immunity
Medical subject headings
Hypoxia, Hyperoxia, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LipopolysaccharideDrug

    Also called Purified LPS from Escherischa coli (O:113)

    LPS is used to elicit an inflammatory response in all subjects

Study groups in NCT01978158
Study groupRoleWhat they receive
HypoxiaExperimentalSubjects will be breathing an individualized mix of nitrogen and room air titrated to an oxygen saturation of 80-85%.
Receives: Drug: Lipopolysaccharide
HyperoxiaExperimentalSubjects will be breathing 100% of oxygen
Receives: Drug: Lipopolysaccharide
NormoxiaActive comparatorSubjects wil be breathing room air (21%)
Receives: Drug: Lipopolysaccharide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Plasma TNF-alpha concentration following LPS administration

    Plasma TNF-α concentration after LPS administration (Area Under Curve); comparison of subjects treated with hypoxia compared to normoxia and hyperoxia compared to hypoxia

    Measured: 1 day

Secondary outcomes (28)

  1. Hypoxia Inducible Factor 1 alpha in circulating leukocytes

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

    Measured: 1 day

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

    Measured: 24 hours

  3. Reactive Oxygen Species in circulating leukocytes

    Measured: 1 day

  4. Phagocytic function of circulating leukocytes

    Measured: 1 day

  5. cytokine production after ex vivo stimulation of leukocytes

    Measured: 1 day

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

    Measured: 1 day

  7. Hemodynamic parameters

    Blood pressure, heart frequency, cardiac output measurement

    Measured: 1 day

  8. ventilatory response

    Measures of ventilation: respiratory rate, blood gas changes

    Measured: 1 day

  9. adenosine metabolism

    urine and plasma adenosine,adenosine receptor mRNA, purines

    Measured: 1 day

  10. alkaline phosphatase

    Measured: 1 day

  11. cognitive function

    neuropsychologic assessment of cognitive function

    Measured: 1 day

  12. Hepcidin and iron parameters

    Measured: 1 day

  13. catecholamines and cortisol

    adrenaline, noradrenaline, dopamine and cortisol

    Measured: 1 day

  14. Neutrophilic function

    Measured: 1 day

  15. body temperature

    Measured: 1 day

  16. oxygen saturation and arterial blood gas

    Measured: 1

  17. subjective symptom scores

    Measured: 1 day

  18. high sensitive troponine

    Measured: 1 day

  19. iFABP

    Measured: 1 day

  20. brain specific proteins

    Measured: 1 day

  21. endocan

    Measured: 1 day

  22. downstream targets of HIF

    adrenomedullin, VEGF, EPO

    Measured: 1 day

  23. heart rate variability

    Measured: 1 day

  24. kidney injury markers in plasma and urine

    Measured: 2 days

  25. microbiome in feces

    Measured: -1 day untill 1 week

  26. markers of immunoparalysis

    monocytic histone 3 lysine 4 trimethylation of the promotor region of pro-inflammatory genes, ex viv production of proinflammatory cytokines, HLA-DR expression on moncytes.

    Measured: 1 day

  27. measures of coagulation and plateletfunction

    platelet activation and platelet function, thrombin generation and other coagulation parameters, hematolocial infection profile using hematology analyser

    Measured: 1 day

  28. meausures of coagulation and fibrinolysis

    thrombin generation, thrombocyte function, ROTEM, plasmatic coagulation, fibrinolysis parameters

    Measured: 1 day

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Nov 2013 (estimated)
  2. Study startOct 2013
  3. Primary completionDec 2013
  4. Study completionDec 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01978158
Sponsor's protocol ID
OX2
Other IDs
2013-002390-21, NL44630.091.13, 2013/290
Status last verified
May 2015
First submitted
31 Oct 2013
Last updated
20 May 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Lipopolysaccharide in people with Hypoxia and Normoxia, run by Radboud University Medical Center at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 May 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plasma TNF-alpha concentration following LPS administration (time frame: 1 day). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01978158.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2015.

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