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

NCT01349699 | Completed DMC

• 1 other identifier: 2009/189
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Systemic Inflammatory Process; Anemia

Keywords

endotoxemia; inflammation; iron; iron chelation; cytokines

Outcome Measures

Primary Outcomes (1)

• TNF-alfa

  Level of TNF-alfa 90 minutes after endotoxin administration

  Level of TNF-alfa 90 minutes after endotoxin administration

Secondary Outcomes (3)

• Cytokines

  24 hrs after the administration of endotoxin

• Oxidative stress

  24 hrs after the administration of iron / iron chelator / placebo

• Hemodynamic response

  24 hours after the administration of endotoxin

Study Arms (3)

Iron loading

ACTIVE COMPARATOR

Subjects will receive 1.25 mg/kg iron sucrose intravenously 1 hour before endoxin administration 2ng/kg.

Drug: iron sucrose; Drug: endotoxin

Iron chelation

ACTIVE COMPARATOR

Subjects will receive 30mg/kg deferasirox orally 2 hours before endotoxin administration 2ng/kg.

Drug: Deferasirox; Drug: endotoxin

Placebo

PLACEBO COMPARATOR

Subjects will receive placebo instead of iron chelation or iron loading before endotoxin administration

Drug: endotoxin; Drug: Placebo

Interventions

iron sucrose DRUG

1.25 mg/kg iron sucrose is administered intravenously 1 hr before endotoxin administration

Also known as: Venofer

Iron loading

Deferasirox DRUG

30 mg/kg deferasirox is administered orally 2 hrs before endotoxin administration.

Also known as: Exjade

Iron chelation

endotoxin DRUG

at t=0 2ng/kg purified E.Coli endotoxin is administered intravenously

Also known as: LPS

Iron chelation; Iron loading; Placebo

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

MeSH Terms

Conditions

Anemia; Endotoxemia; Inflammation

Interventions

Ferric Oxide, Saccharated; Deferasirox; Endotoxins

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Bacteremia; Sepsis; Infections; Toxemia; Systemic Inflammatory Response Syndrome; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ferric Compounds; Iron Compounds; Inorganic Chemicals; Glucaric Acid; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Benzoates; Acids, Carbocyclic; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Bacterial Toxins; Toxins, Biological; Biological Factors

Study Officials

• Peter Pickkers, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD. PhD

Study Record Dates

• First Submitted: May 5, 2011
• First Posted: May 6, 2011
• Study Start: February 1, 2010
• Primary Completion: May 1, 2010
• Study Completion: September 1, 2010
• Last Updated: November 17, 2015

Record last verified: 2015-11