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Effects of Iron Loading and Iron Chelation Therapy on Innate Immunity During Human Endotoxemia

This study has been completed.
Sponsor:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT01349699
First received: May 5, 2011
Last updated: June 6, 2011
Last verified: January 2010
History of Changes
  Purpose

Iron affects immunity. However, the exact effect of iron on the innate immune response is not known. Animal data suggest that iron administration induced oxidative stress which enhances the innate immune response, whereas iron chelation has the opposite effect. The investigators tested the hypothesis that administration of iron sucrose 1.25 mg/kg augments the innate immune response, and iron chelation by deferasirox 30 mg/kg attenuates the innate immune response during human experimental endotoxemia.


Condition Intervention
Systemic Inflammation
Iron Loading
Iron Chelation
 Drug: iron sucrose
Drug: Deferasirox
Drug: endotoxin
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of Iron Loading and Iron Chelation Therapy on Innate Immunity During Human Endotoxemia

Resource links provided by NLM:

MedlinePlus related topics: Iron
U.S. FDA Resources

Further study details as provided by Radboud University:

Primary Outcome Measures:
  • TNF-alfa [ Time Frame: Level of TNF-alfa 90 minutes after endotoxin administration ] [ Designated as safety issue: No ]
    Level of TNF-alfa 90 minutes after endotoxin administration


Secondary Outcome Measures:
  • Cytokines [ Time Frame: 24 hrs after the administration of endotoxin ] [ Designated as safety issue: No ]
    Levels of TNF-alfa, IL-6, IL-10 IL-1RA, ICAM and VCAM.

  • Oxidative stress [ Time Frame: 24 hrs after the administration of iron / iron chelator / placebo ] [ Designated as safety issue: No ]

    Several parameters of oxidative stress are measured:

    TBARS,carbonyls,oxidative radical production of neutrophils, ferric reducing ability of plasma.


  • Hemodynamic response [ Time Frame: 24 hours after the administration of endotoxin ] [ Designated as safety issue: Yes ]
    Hemodynamic sequelae of endotoxine administration are monitored (heart rate, blood pressure) and the response of fore arm vessels to the infusion of vasoactive medication (noreponephrine, acetycholine, and nitroglycerine) is measured.


Enrollment: 30
Study Start Date: February 2010
Study Completion Date: September 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Iron loading
Subjects will receive 1.25 mg/kg iron sucrose intravenously 1 hour before endoxin administration 2ng/kg.
 Drug: iron sucrose
1.25 mg/kg iron sucrose is administered intravenously 1 hr before endotoxin administration
Other Name: Venofer
Drug: endotoxin
at t=0 2ng/kg purified E.Coli endotoxin is administered intravenously
Other Name: LPS
Active Comparator: Iron chelation
Subjects will receive 30mg/kg deferasirox orally 2 hours before endotoxin administration 2ng/kg.
 Drug: Deferasirox
30 mg/kg deferasirox is administered orally 2 hrs before endotoxin administration.
Other Name: Exjade
Drug: endotoxin
at t=0 2ng/kg purified E.Coli endotoxin is administered intravenously
Other Name: LPS
Placebo Comparator: Placebo
Subjects will receive placebo instead of iron chelation or iron loading before endotoxin administration
 Drug: endotoxin
at t=0 2ng/kg purified E.Coli endotoxin is administered intravenously
Other Name: LPS
Drug: Placebo

At t=-2 hrs starch is dissolved in water to serve as a placebo for exjade. It is prepared and administered orally by a research nurse that is unblinded to the protocol.

At t=-1 hrs 0.9% NaCl is administered intravenously serving as a placebo for iron sucrose. The infused volume is identical, and the syringes en tubes are blinded by aluminum foil. The administration is carried out by a research nurse that is unblinded to the protocol.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • male
  • healthy
  • between 18 and 35 years of age

Exclusion Criteria:

  • smoking
  • use of prescription drugs
  • febrile illness < 2 weeks before the study date
  • abnormalities found at screening
  • participation in another trial in the preceding 6 months
  • iron disorders in the family
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01349699

Sponsors and Collaborators
Radboud University
ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
Principal Investigator: Peter Pickkers, MD, PhD Radboud University
  More Information

No publications provided

Responsible Party: Professor P. Pickkers, Principle Investigator, Radboud University Nijmegen Medical Centre
ClinicalTrials.gov Identifier: NCT01349699     History of Changes
Other Study ID Numbers: 2009/189
Study First Received: May 5, 2011
Last Updated: June 6, 2011
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
endotoxemia
inflammation
iron
iron chelation
cytokines

Additional relevant MeSH terms:
Inflammation
Endotoxemia
Pathologic Processes
Bacteremia
Sepsis
Infection
Toxemia
Systemic Inflammatory Response Syndrome
Ferric oxide, saccharated
Iron
Deferasirox
 Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Iron Chelating Agents
Chelating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 19, 2013