NCT00916448

The Effects of Atazanavir-induced Hyperbilirubinemia During Human Endotoxemia

The Effects of Atazanavir-induced Hyperbilirubinemia on the Innate Immune Response During Human Endotoxemia. A Parallel Double Blind Placebo Controlled Pilot Study.

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Radboud University Medical Center · Academic / Other
• Sex: Male
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

Summary

Excessive inflammation, production of free radicals and vascular injury are considered the main contributors to the development of organ dysfunction in patients with severe infections and sepsis. The endogenously produced unconjugated bilirubin is one of the most powerful anti-oxidants of the human body and the administration of bilirubin in animal experiments has been shown to protect from inflammation-induced death. However, bilirubin for human administration is not yet available. Therefore, we wish to exploit one of the side effects of atazanavir, a registered drug currently used as a protease inhibitor in HIV infected patients. Atazanavir inhibits the enzyme UPD glucuronosyl transferase enzyme (UGT1A1) and therefore increases endogenously produced bilirubin levels moderately. To study the effect of hyperbilirubinemia during inflammation we will apply the human endotoxemia model. The human endotoxemia model permits elucidation of key players in the immune response to a gram negative stimulus in vivo, therefore serving as a useful tool to investigate potential novel therapeutic strategies in a standardized setting. We hypothesize that atazanavir-induced hyperbilirubinemia has beneficial anti-inflammatory and vascular effects during human endotoxemia.

Conditions

• Endotoxemia
• Inflammation
• Multi Organ Dysfunction Syndrome
• Sepsis

Interventions

Type	Name	Description
DRUG	Atazanavir	capsules of 150 mg, 2 capsules, twice daily on 4 consecutive days
DRUG	E. coli endotoxin	2 ng/kg E. coli reference endotoxin 11:H 10:K negative intravenously

Timeline

• Start date: 2009-05-01
• Primary completion: 2010-03-01
• Completion: 2015-07-01
• First posted: 2009-06-09
• Last updated: 2015-08-14

Locations

1 site across 1 country: Netherlands