Aminotransferase Trends During Prolonged Acetaminophen Dosing
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Purpose
The objective of this study is to monitor liver function tests (blood levels of an indicator of liver function) of healthy people taking the maximum labeled daily dose of acetaminophen compared to people taking placebo for 16 to 40 days. Those people that continue to have normal liver tests after 16 days will have completed their part of the study. People that develop abnormal liver function tests will continue taking acetaminophen or placebo, and have their liver tests monitored closely for up to an additional 24 days. This is to (1) make sure these tests return to normal and (2) determine when these tests return to normal while still taking acetaminophen or placebo. If at any time the liver tests indicate anything more than a minor increase, you would be immediately told to stop taking the study drug.
Secondary objective is to determine the proportion of subjects that have detectable acetaminophen-protein adducts after daily dosing.
| Condition | Intervention | Phase |
|---|---|---|
|
Drug Toxicity Healthy |
Drug: acetaminophen Drug: placebo |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) |
| Official Title: | Aminotransferase Trends During Prolonged Therapeutic Acetaminophen Dosing |
- alanine aminotransferase (ALT) [ Time Frame: serial samples over 17-42 days ] [ Designated as safety issue: Yes ]
- acetaminophen-protein adducts [ Time Frame: serial samples for 16-42 days ] [ Designated as safety issue: Yes ]
| Enrollment: | 398 |
| Study Start Date: | August 2008 |
| Study Completion Date: | August 2011 |
| Primary Completion Date: | August 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 1
acetaminophen
|
Drug: acetaminophen
500 mg caplets; 2 capsules (1 g)/dose; 4 doses (4 g)/day, 4 hours apart for 16 to 40 days.
Other Name: tylenol
|
|
Placebo Comparator: 2
placebo
|
Drug: placebo
placebo caplets, 2 caplets per dose, 4 doses per day, 4 hours apart for 16 to 40 days
Other Name: placebo
|
Detailed Description:
Acetaminophen use is common and many consumers take 4g/day for longer than 4 days. The use of 4g/day of acetaminophen for more than 4 days causes an asymptomatic ALT elevation in some people. This elevation most likely resolves while continuing treatment, but it is possible that some individuals may go on to develop clinical liver injury. By carefully following healthy subjects who are taking the maximal daily dose of acetaminophen, we can safely determine if the ALT elevation resolves or progresses to clinical liver injury. If a subject develops clinical liver injury we can intervene before irreversible injury occurs.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- age 18 or older
Exclusion Criteria:
- History of acetaminophen ingestion on any of the four days preceding study enrollment
- Measurable serum acetaminophen level at time of enrollment
- Viral markers of Hepatitis B or C, or viral markers of Hepatitis A with an ALT level greater than ULN during screening laboratory testing
- Serum ALT or AST level greater than ULN at Screening or Day 0
- Total bilirubin level greater than ULN at Screening or Day 0
- INR level greater than ULN at Screening
- Alkaline phosphatase level greater than ULN at Screening
- Platelet count less than 125 10^9/L at Screening
- Known cholelithiasis
- Positive pregnancy test at Screening (female participants only)
- History of consuming more than an average of 3 alcohol containing drinks daily over the preceding 2 weeks
- History of consuming 3 or more alcohol containing drinks on any given day during the 2 weeks prior to study enrollment
- New prescription medication started within the previous 30 days
- Currently taking isoniazid
- Currently taking warfarin
- Currently adheres to a fasting type diet as determined by self report
- Currently has anorexia nervosa as determined by self report
- Participant is clinically intoxicated, psychiatrically impaired or unable to give informed consent for any reason
- Known hypersensitivity or allergy to acetaminophen
Contacts and Locations| United States, Colorado | |
| University of Colorado Health Sciences Center - GCRC | |
| Aurora, Colorado, United States, 80045 | |
| Denver Health Rocky Mountain Poison and Drug Center | |
| Denver, Colorado, United States, 80204 | |
| Principal Investigator: | Kennon Heard, MD | Denver Health/Rocky Mountain Poison & Drug Center |
More Information
Publications:
| Responsible Party: | Kennon Heard, Fellowship Director, Denver Health and Hospital Authority |
| ClinicalTrials.gov Identifier: | NCT00743093 History of Changes |
| Other Study ID Numbers: | COMIRB #06-1265 |
| Study First Received: | August 26, 2008 |
| Last Updated: | August 7, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Denver Health and Hospital Authority:
|
acetaminophen protein adducts drug safety alanine aminotransferase Alanine Amino Transferase |
Additional relevant MeSH terms:
|
Drug Toxicity Poisoning Substance-Related Disorders Acetaminophen Antipyretics Physiological Effects of Drugs Pharmacologic Actions |
Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Central Nervous System Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 23, 2013