Cytokines Polymorphisms and Acetaminophen Toxicity

Completed

• Conditions: Drug Toxicity

• Registration Number: NCT00166608
• Lead Sponsor: Arkansas Children's Hospital Research Institute

Brief Summary

Genotyping assays for polymorphisms in the interleukin 10(IL10)gene and the inducible nitric oxide synthase (iNOS) gene will be performed. Genotypes will be compared to the severity of toxicity following overdose.

Detailed Description

It was recently reported that IL-10 is protective in Acetaminophen (APAP) toxicity and it down-regulates iNOS production. In an ongoing Pediatric Pharmacology Research Unit (PPRU) Network study, plasma IL-10 levels were higher in patients that developed significant toxicity, as compared to those with minimal hepatic transaminase elevations. In these patients IL-10 elevation is likely a compensatory response to hepatic injury. To further examine the relationship of IL-10 and iNOS in the APAP overdose patients, we will examine genetic variability in the promotor regions of iNOS and IL-10 in patients with APAP overdose. Data from the literature indicate the polymorphisms in the promotor regions of iNOS and IL-10 influence the severity and expression of various diseases. In addition to genotyping for iNOS and IL10 promotor region polymorphisms, plasma levels of nitrotyrosine and IL-10 will be measured in overdose patients.

Blood samples will be obtained from study patients for the analysis of inflammatory cytokines and nitrotyrosine. Blood samples will be obtained at the time of blood sampling for the routine clinical management of the APAP overdose patient. Patients who are hospitalized will have study blood samples drawn at the time daily blood samples are obtained. The sampling will continue daily until the patient is discharged. In addition to blood sampling the following data will be collected: age, gender, race, circumstances of the ingestion, dose of the ingestion, treatment for the ingestion, concomitant therapy, medical history and cigarette use.

Study Timeline

• Study Start: 2002-12
• Study First Submitted: 2005-09-09
• Study First Submitted QC: 2005-09-09
• Study First Posted: 2005-09-14
• Primary Completion: 2007-05
• Study Completion: 2007-09
• Status Verified: 2012-04
• Last Update Submitted: 2012-04-10
• Last Update Posted: 2012-04-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 111

Inclusion Criteria

• Males and females of any age admitted to a participating site for acetaminophen overdose (acute or chronic).

Exclusion Criteria

• Patients who are unable to tolerate study procedures.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To investigate the relationships of cytokines and toxicity in acetaminophen overdose, blood sampleswere collected from patients following acute ingestions of acetaminophen.

Trial Locations

Locations (7)

Kosair Children's Hospital; 🇺🇸 Louisville, Kentucky, United States

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

Children's Mercy Hospital; 🇺🇸 Kansas City, Missouri, United States

University of North Carolina--Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Rainbow Babies & Children's Hospital; 🇺🇸 Cleveland, Ohio, United States

Texas Children's Hospital; 🇺🇸 Houston, Texas, United States

Children's Hospital of Michigan; 🇺🇸 Detroit, Michigan, United States