Acetaminophen ExposurePhase 4NCT02911961
APAP-CYS Protein Adduct Concentrations in Patients With Liver-Directed Therapy Intended to Treat Hepatic Tumors
A Phase 4 study testing Acetaminophen in people with Acetaminophen Exposure, run by Denver Health and Hospital Authority at 1 site in United States.
Trial summary
The objective of this study is to provide preliminary data to describe serum acetaminophen-cysteine protein adduct (APAP-CYS) concentrations following therapeutic doses of acetaminophen in the setting of non-acetaminophen induced liver injury. This study will utilize hepatic embolization as a model of hepatic injury. Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Acetaminophen Exposure
- What is being tested?
- Acetaminophen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2021to Aug 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects of any gender or ethnic background who are between 21 and 80 years old
- Subjects who are able to provide written, informed consent
- Subjects with secondary liver cancer
- Subjects undergoing portal vein or bland embolization for the treatment of secondary hepatic tumor
- Subjects who are willing to have their blood drawn at least 12 times for study purposes
- Subjects who agree to stay for ~18-21 hours after being discharged from the Department of Radiology for research purposes
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- Subjects who agree to refrain from using acetaminophen, other than the study drug, during the dosing phase through a minimum of 5 days post-procedure
- Subjects who agree to consume less than 3 alcoholic drinks per day while taking study drug (acetaminophen group only)
- Subjects who are willing to complete a study diary for 3 days prior to and the day of the procedure
- Subjects who will be in the Denver metro area for the duration of the study
Who cannot join
- Subjects with known cirrhosis
- Subjects with a history of moderate to severe anemia at screening as defined by:
- Moderate: Hemoglobin 8-9.5 g/dL
- Severe: Hemoglobin <8 g/dL
- Subjects with an ALT or AST greater than 200 IU/L at screening
- Subjects with a total bilirubin greater than 1.5 mg/dL at screening
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- Subjects with an INR greater than 1.3 at screening
- Subjects with a platelet count less than 125 10^9/L at screening
- Subjects who are currently taking warfarin (acetaminophen group only)
- Subjects with anorexia nervosa (self-reported; acetaminophen group only)
- Subjects who weigh ≤50 kg at screening (acetaminophen group only)
- Subjects who adhere to a fasting type diet (self-reported; acetaminophen group only)
- Subjects with a known hypersensitivity or allergy to acetaminophen (acetaminophen group only)
- Subjects who are currently taking isoniazid (acetaminophen group only)
- Subjects who are currently taking disulfiram (acetaminophen group only)
- Subjects who are pregnant or breastfeeding (female participants only)
- Subjects who are currently enrolled in a clinical trial, have participated in a clinical trial within the 30 days prior to the procedure, or who plan to participate in a clinical trial during the 5 day post-procedure follow-up period
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver
Denver, Colorado, 80045
About this study
Official title: Serum Acetaminophen-Cysteine (APAP-CYS) Adduct Concentrations in Subjects Expected to Develop Aminotransferase Elevations With Liver-Directed Therapy Intended to Treat Hepatic Tumors
The objective of this study is to provide preliminary data to describe serum acetaminophen-cysteine protein adduct (APAP-CYS) concentrations following therapeutic doses of acetaminophen in the setting of non-acetaminophen induced liver injury. This study will utilize hepatic embolization as a model of hepatic injury.
Read the detailed description
Acetaminophen-cysteine protein adducts (APAP-CYS) are formed when acetaminophen is oxidized by CYP 2E-1. When hepatocytes die, these proteins are released into the serum and can be detected. APAP-CYS can therefore be an experimental biomarker of acetaminophen exposure. It is possible that massive necrosis of hepatocytes that contain APAP-CYS from therapeutic doses of acetaminophen can be misinterpreted as acetaminophen overdose as the cause of liver injury. This study aims to describe serum APAP-CYS concentrations in patients taking a therapeutic dose of acetaminophen who develop a liver injury from a cause other than acetaminophen. This study will seek to enroll subjects undergoing a hepatic embolization procedure to treat a secondary liver tumor. This procedure is a reproducible model of non-acetaminophen induced hepatic injury. A small number of subjects who are otherwise eligible to participate but are unwilling to take acetaminophen will be offered participation in the observational arm of the study. They will undergo the same assessments with the exception of acetaminophen dosing. Subjects willing to take acetaminophen will be asked to take extra strength acetaminophen (4g/day) for the 3 days prior to their embolization procedure. All subjects will be asked to keep a detailed medication diary for the three days prior and up to their embolization procedure. Blood samples for the measurement of APAP-CYS concentrations and markers of liver function will be collected prior to acetaminophen dosing, prior to the embolization procedure, and at several time points after the procedure.
- Conditions
- Acetaminophen Exposure
- Being tested
- Acetaminophen
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetaminophenDrug
Also called Tylenol
1 gram acetaminophen 4 times a day with at least 6 hour intervals between doses for the 3 days prior to the embolization procedure.
| Study group | Role | What they receive |
|---|---|---|
| Acetaminophen | Experimental | Subjects will take extra strength acetaminophen (4g/day) for the three days prior to the embolization procedure. Receives: Drug: Acetaminophen |
| Observational - No Acetaminophen | No intervention | Subjects will take no acetaminophen containing products prior to the embolization procedure. |
What is being measured
The primary outcome is the main question the study is designed to answer.
APAP-CYS Concentrations Over Time - Acetaminophen Group
To describe the course of APAP-CYS concentrations following hepatic embolization in subjects who receive 4 grams/day of acetaminophen for three days prior to the procedure
Measured: 14 days
Secondary outcomes (2)
APAP-CYS Concentrations Over Time - Non-Acetaminophen Group
To determine if subjects who report no exposure to acetaminophen prior to the procedure have detectable APAP-CYS concentrations
Measured: 2 years
Relationship between APAP-CYS and other biochemical markers of liver function
To evaluate the relationship between APAP-CYS concentrations with aspartate aminotransferase (AST), alanine aminotransferase (ALT), and miRNA activity
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2016 (estimated)
- Study startAug 2021 (estimated)
- Primary completionAug 2021 (estimated)
- Study completionAug 2021 (estimated)
Why it stopped: Due to lack of enrollment and organizational desire to focus recruitment efforts on other studies.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acetaminophen ExposureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Denver Health and Hospital Authority
- Sponsor type
- University, hospital or other
- Collaborators
- Johnson & Johnson Consumer Inc., McNeil Consumer Healthcare Division, University of Colorado, Denver, Rocky Mountain Poison and Drug Center
- Responsible party
- Principal investigator, Kennon Heard, Denver Health and Hospital Authority
- Investigators
- Kennon Heard, MD, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02911961
- Sponsor's protocol ID
- 16-0031
- Status last verified
- Aug 2021
- First submitted
- 17 Aug 2016
- Last updated
- 2 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Serum Acetaminophen-Cysteine (APAP-CYS) Adduct Concentrations in Subjects Expected to Develop Aminotransferase Elevations With Liver-Directed Therapy Intended to Treat Hepatic Tumors
- ClinicalTrials.gov ID
- NCT02911961
- Acronym / sponsor ID
- 16-0031
- Conditions
- Acetaminophen Exposure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Due to lack of enrollment and organizational desire to focus recruitment efforts on other studies.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Denver Health and Hospital AuthorityUniversity, hospital or other
- Collaborators
- Johnson & Johnson Consumer Inc., McNeil Consumer Healthcare Division, University of Colorado, Denver, Rocky Mountain Poison and Drug Center
- Study start
- Aug 2021 (estimated)
- Primary completion
- Aug 2021 (estimated)
- Study completion
- Aug 2021 (estimated)
- First posted
- 23 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to provide preliminary data to describe serum acetaminophen-cysteine protein adduct (APAP-CYS) concentrations following therapeutic doses of acetaminophen in the setting of non-acetaminophen induced liver injury. This study will utilize hepatic embolization as a model of hepatic injury.
Detailed description
Acetaminophen-cysteine protein adducts (APAP-CYS) are formed when acetaminophen is oxidized by CYP 2E-1. When hepatocytes die, these proteins are released into the serum and can be detected. APAP-CYS can therefore be an experimental biomarker of acetaminophen exposure. It is possible that massive necrosis of hepatocytes that contain APAP-CYS from therapeutic doses of acetaminophen can be misinterpreted as acetaminophen overdose as the cause of liver injury. This study aims to describe serum APAP-CYS concentrations in patients taking a therapeutic dose of acetaminophen who develop a liver injury from a cause other than acetaminophen. This study will seek to enroll subjects undergoing a hepatic embolization procedure to treat a secondary liver tumor. This procedure is a reproducible model of non-acetaminophen induced hepatic injury. A small number of subjects who are otherwise eligible to participate but are unwilling to take acetaminophen will be offered participation in the observational arm of the study. They will undergo the same assessments with the exception of acetaminophen dosing. Subjects willing to take acetaminophen will be asked to take extra strength acetaminophen (4g/day) for the 3 days prior to their embolization procedure. All subjects will be asked to keep a detailed medication diary for the three days prior and up to their embolization procedure. Blood samples for the measurement of APAP-CYS concentrations and markers of liver function will be collected prior to acetaminophen dosing, prior to the embolization procedure, and at several time points after the procedure.
Study design
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acetaminophen | Experimental | Drug: AcetaminophenSubjects will take extra strength acetaminophen (4g/day) for the three days prior to the embolization procedure. |
| Observational - No Acetaminophen | No intervention | –Subjects will take no acetaminophen containing products prior to the embolization procedure. |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Subjects of any gender or ethnic background who are between 21 and 80 years old
- Subjects who are able to provide written, informed consent
- Subjects with secondary liver cancer
- Subjects undergoing portal vein or bland embolization for the treatment of secondary hepatic tumor
- Subjects who are willing to have their blood drawn at least 12 times for study purposes
Key exclusion criteria (17 listed)
- Subjects with known cirrhosis
- Subjects with a history of moderate to severe anemia at screening as defined by:
- Subjects with an ALT or AST greater than 200 IU/L at screening
- Subjects with a total bilirubin greater than 1.5 mg/dL at screening
- Subjects with an INR greater than 1.3 at screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcetaminophenAlso: Tylenol1 gram acetaminophen 4 times a day with at least 6 hour intervals between doses for the 3 days prior to the embolization procedure. | Drug | Acetaminophen |
Primary outcome
APAP-CYS Concentrations Over Time - Acetaminophen Group
Time frame: 14 days
To describe the course of APAP-CYS concentrations following hepatic embolization in subjects who receive 4 grams/day of acetaminophen for three days prior to the procedure
2 secondary outcomes
APAP-CYS Concentrations Over Time - Non-Acetaminophen Group
Time frame: 2 years
Relationship between APAP-CYS and other biochemical markers of liver function
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2021.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kennon Heard, MD, PhD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Acetaminophen in people with Acetaminophen Exposure, run by Denver Health and Hospital Authority at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 2 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
APAP-CYS Concentrations Over Time - Acetaminophen Group (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2021.