Cytokines Polymorphisms and Acetaminophen Toxicity

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00166608
Recruitment Status : Completed
First Posted : September 14, 2005
Last Update Posted : April 12, 2012
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by:
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.

Condition or disease Intervention/treatment
Drug Toxicity Procedure: Blood sampling

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 Type : Observational
Actual Enrollment : 111 participants
Time Perspective: Prospective
Official Title: Measurement of Nitrotyrosine Adducts and Cytokines in Acetaminophen Overdose Patients
Study Start Date : December 2002
Actual Primary Completion Date : May 2007
Actual Study Completion Date : September 2007

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. To investigate the relationships of cytokines and toxicity in acetaminophen overdose, blood sampleswere collected from patients following acute ingestions of acetaminophen.

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Publication Attached

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00166608

United States, Arkansas
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202
United States, Kentucky
Kosair Children's Hospital
Louisville, Kentucky, United States, 40202
United States, Michigan
Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, North Carolina
University of North Carolina--Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Rainbow Babies & Children's Hospital
Cleveland, Ohio, United States, 44106
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Arkansas Children's Hospital Research Institute
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Laura James, M.D. Arkansas Children's Hospital Research Institute

Additional Information:
Responsible Party: Laura James, M.D., Arkansas Children's Hospital Research Institute Identifier: NCT00166608     History of Changes
Obsolete Identifiers: NCT00147407
Other Study ID Numbers: PPRU-10369s
First Posted: September 14, 2005    Key Record Dates
Last Update Posted: April 12, 2012
Last Verified: April 2012

Keywords provided by Arkansas Children's Hospital Research Institute:
acetaminophen toxicity
liver damage
tylenol overdose

Additional relevant MeSH terms:
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs