Clinical trial NCT00166608: Cytokines Polymorphisms and Acetaminophen Toxicity
Official title: Measurement of Nitrotyrosine Adducts and Cytokines in Acetaminophen Overdose Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Drug Toxicity
Keywords: acetaminophen toxicity
liver damage
tylenol overdose
Lead sponsor: Arkansas Children's Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2005-09-14
Enrollment: 111
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Publication Attached

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.

Eligibility criteria: 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.

Primary outcomes:
measure: To investigate the relationships of cytokines and toxicity in acetaminophen overdose, blood sampleswere collected from patients following acute ingestions of acetaminophen.
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Chapel Hill
country: United States
facility: University of North Carolina--Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Rainbow Babies & Children's Hospital
state: Ohio
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
Study officials:
affiliation: Arkansas Children's Hospital Research Institute
name: Laura James, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: James LP, Simpson PM, Farrar HC, Kearns GL, Wasserman GS, Blumer JL, Reed MD, Sullivan JE, Hinson JA. Cytokines and toxicity in acetaminophen overdose. J Clin Pharmacol. 2005 Oct;45(10):1165-71. doi: 10.1177/0091270005280296.