NCT01889823

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jun 2013

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2013

Completed
25 days until next milestone

First Submitted

Initial submission to the registry

June 26, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 28, 2013

Completed
1 month until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2013

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2014

Completed
Last Updated

March 25, 2015

Status Verified

March 1, 2015

Enrollment Period

2 months

First QC Date

June 26, 2013

Last Update Submit

March 24, 2015

Conditions

HypoxiaHyperoxia

Keywords

OxygenHypoxiaHyperoxiaInflammationInnate immunity

Outcome Measures

Primary Outcomes (1)

  • Hypoxia Inducible Factor 1 alpha in circulating leukocytes

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

    24 hours

Secondary Outcomes (24)

  • Hypoxia Inducible Factor mRNA and anti Hypoxia Inducible Factor mRNA in circulating leukocytes

    24 hours

  • Reactive Oxygen Species in circulating leukocytes

    24 hours

  • Phagocytic function of circulating leukocytes

    24 hours

  • cytokine production after ex vivo stimulation of leukocytes

    24 hours

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

    24 hours

  • +19 more secondary outcomes

Study Arms (2)

Hypoxia

EXPERIMENTAL

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

Other: Hypoxia

Hyperoxia

EXPERIMENTAL

Subjects will be breathing 100% of oxygen

Other: Hyperoxia

Interventions

HypoxiaOTHER

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

Hypoxia
HyperoxiaOTHER

Subjects will be breathing 100% oxygen

Hyperoxia

Eligibility Criteria

Age18 Years - 35 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Age ≥18 and ≤35 yrs
  • Male
  • Healthy

You may not qualify if:

  • 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
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Intensive Care Medicine, Radboud University Nijmegen Medical Centre

Nijmegen, Nijmegen, Gelderland, 6500 HB, Netherlands

Location

MeSH Terms

Conditions

HypoxiaHyperoxiaInflammation

Condition Hierarchy (Ancestors)

Signs and Symptoms, RespiratorySigns and SymptomsPathological Conditions, Signs and SymptomsPathologic Processes

Study Officials

  • Dorien Kiers, MD

    Intensive Care Medicine, Radboud University Nijmegen Medical Centre

    PRINCIPAL INVESTIGATOR

  • Peter Pickkers, MD,PhD

    Intensive Care Medicine, Radboud University Nijmegen Medical Centre

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof. dr. P. Pickkers

Study Record Dates

First Submitted

June 26, 2013

First Posted

June 28, 2013

Study Start

June 1, 2013

Primary Completion

August 1, 2013

Study Completion

December 1, 2014

Last Updated

March 25, 2015

Record last verified: 2015-03

Locations

NL(1)