Acetaminophen-induced Hepatotoxicity in Chronic Alcohol Abusers

It is widely believed that people who abuse alcohol can sustain a liver injury after taking doses of acetaminophen just above the recommended maximum dose. This study is designed to look at the interaction between acetaminophen, liver injury and alcohol abuse. Subjects will undergo baseline tests to ensure that they do not have liver damage at the time of enrollment. Each subject will be randomly assigned to receive either a therapeutic dose of acetaminophen or a placebo three times a day for four days. Subjects will have blood work drawn on a daily basis to monitor the status of the liver. These tests will include conventional markers of liver injury in addition to a novel biomarker of liver function, a-GST. Previous work in the investigators' group has shown that a-GST is a more sensitive indicator of liver injury following acetaminophen overdose (Sivilotti 1999, Sivilotti 2002 x 2). However, it has never been used to study the alcoholic population. The investigators believe that a-GST may detect a subclinical acetaminophen-induced liver injury that has previously gone unrecognized in the alcoholic population.

Study Overview

• Status: Completed
• Conditions: Hepatotoxicity
• Intervention / Treatment: Drug: acetaminophen sustained-release

• Study Type: Interventional
• Enrollment: 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L 3N6
      • Queen's University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Individuals who self-report consuming at least 6 drinks per day, daily, for at least 6 weeks and who are currently enrolled at the Detoxification Center, Hotel Dieu Hospital.
• Last alcohol consumption occurring between 12 and 72 hours prior to screening for study.

Exclusion Criteria:

• Individuals with a self-reported or previously documented history of hepatitis A, B, C or HIV.
• Individuals who have ingested any acetaminophen regardless of dose in the previous 48 hours.
• Individuals who have ingested > 4 grams of acetaminophen/day in any of the previous 7 days.
• Individuals < 18 years of age.
• Individuals with abnormal liver function at baseline (defined as AST or ALT > 120 IU/L, International Normalized Ratio [INR] > 1.5, and a-GST > 7.5 7 :g/L).
• Individuals who have an allergy or sensitivity to acetaminophen.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
serum a-GST relative to baseline

Secondary Outcome Measures

Outcome Measure
conventional liver function tests (LFTs)

Collaborators and Investigators

• Sponsor: Dr. Marco L.A. Sivilotti
• Investigators: Principal Investigator: Marco LA Sivilotti, MD, MSc, Queen's University

Publications and helpful links

General Publications

• Bartels S, Sivilotti M, Crosby D, Richard J. Are recommended doses of acetaminophen hepatotoxic for recently abstinent alcoholics? A randomized trial. Clin Toxicol (Phila). 2008 Mar;46(3):243-9. doi: 10.1080/15563650701447020.

Study record dates

Study Major Dates

• Study Start: November 1, 2002
• Study Completion: May 1, 2005

Study Registration Dates

• First Submitted: August 26, 2005
• First Submitted That Met QC Criteria: August 26, 2005
• First Posted (Estimated): August 29, 2005

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: PSI R02-52