PainPhase 4NCT00768716

Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics

A Phase 4 study testing Acetaminophen in people with Pain and Fever, run by Tufts University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 64 yearsHealthy volunteers can take part
Conditions the study is for: Pain, Fever, Hepatotoxicity
What is being tested?: Acetaminophen
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 95 participants
Where: 1 siteUnited States
Study dates: Dec 2008to Dec 2013
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 18 to 64 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

self-declared white/Caucasian
self-declared African-American
active
ambulatory
no evidence of medical disease

Who cannot join

alcohol use of 3 or more drinks per day
HIV or hepatitis (B or C) infection
isoniazid
disulfiram
phenobarbital
phenytoin

Show all 11Show fewer

carbamazepine
rifampicin
valproic acid
probenecid
St. John's Wort

Trial locations and contacts

1 site in 1 country.

United States1 site

Tufts Clinical Pharmacology Study Unit
Boston, Massachusetts, 02111

Other trials in United States

About this study

Although acetaminophen is the most commonly used nonprescription drug in the USA, little is known regarding the influence of genes and race/ethnicity on acetaminophen disposition. The investigators long-term goal is to understand the causes of differences in acetaminophen disposition between people that are the result of genetic variation and ethnicity and may predispose individuals to a higher risk of acetaminophen hepatotoxicity. The aim of this particular study is to measure the rate of elimination of acetaminophen via the 3 main pathways (glucuronidation, sulfation and oxidation) in self-identified White-Americans (n=100) and African-Americans (n=100). These rates will then be correlated with selected genetic polymorphisms in genes encoding enzymes involved in acetaminophen metabolism. Two main hypotheses will be tested: 1. African-Americans eliminate acetaminophen more rapidly by glucuronidation than do White-Americans. 2. Elimination via glucuronidation, sulfation, and oxidation in subjects will be significantly correlated with the presence of polymorphisms in the UGT1A6, SULT1A1, and CYP2E1 genes, respectively.

Conditions: Pain, Fever, Hepatotoxicity
Being tested: Acetaminophen
Medical subject headings: Pain, Fever

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AcetaminophenDrug
Also called Tylenol
2 x 500 mg by mouth once

Study groups in NCT00768716
Study group	Role	What they receive
White subjects	Experimental	2 x 500 mg acetaminophen by mouth once Receives: Drug: Acetaminophen
Black subjects	Experimental	2 x 500 mg acetaminophen by mouth once Receives: Drug: Acetaminophen

What is being measured

The primary outcome is the main question the study is designed to answer.

Acetaminophen Plasma Clearance Association With Race/Ethnicity
Plasma total clearance of acetaminophen in plasma measured by HPLC
Measured: 2 days
Acetaminophen Glucuronidation Partial Clearance Association With Race/Ethnicity
Acetaminophen glucuronidation partial clearance determined from plasma clearance and urinary metabolite excretion
Measured: 2 days
Acetaminophen Sulfation Partial Clearance Association With Race/Ethnicity
Acetaminophen sulfation partial clearance determined from plasma clearance and urinary metabolite excretion
Measured: 2 days
Acetaminophen Oxidation Partial Clearance Association With Race/Ethnicity
Acetaminophen oxidation partial clearance determined from plasma clearance and urinary metabolite excretion
Measured: 2 days
Acetaminophen Plasma Clearance Association With UGT2B15 Genotype
The association of UGT2B15 genotype with acetaminophen total clearance
Measured: 2 days
Acetaminophen Glucuronidation Partial Clearance Association With UGT2B15 Genotype
The association of acetaminophen glucuronidation partial clearance with UGT2B15 genotype
Measured: 2 days
APAP Plasma Adduct Association With UGT2B15 Genotype
The association of UGT2B15 genotype with APAP plasma adduct concentrations
Measured: 2 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2008Dec 2013

First posted8 Oct 2008 (estimated)
Study startDec 2008
Primary completionJun 2012
Study completionDec 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (10)Papers the sponsor has linked to this study.
Other trials for PainStudies 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: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 95 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00768716
Sponsor's protocol ID: 8600
Other IDs: R01GM061834, R01GM102130
Status last verified: May 2019
First submitted: 7 Oct 2008
Last updated: 23 May 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Krishnaswamy S, Hao Q, Al-Rohaimi A, Hesse LM, von Moltke LL, Greenblatt DJ, Court MH. UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: I. Identification of polymorphisms in the 5'-regulatory and exon 1 regions, and association with human liver UGT1A6 gene expression and glucuronidation. J Pharmacol Exp Ther. 2005 Jun;313(3):1331-9. doi: 10.1124/jpet.104.081950. Epub 2005 Mar 10.
PubMed 15761114
Krishnaswamy S, Hao Q, Al-Rohaimi A, Hesse LM, von Moltke LL, Greenblatt DJ, Court MH. UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: II. Functional impact of the three most common nonsynonymous UGT1A6 polymorphisms (S7A, T181A, and R184S). J Pharmacol Exp Ther. 2005 Jun;313(3):1340-6. doi: 10.1124/jpet.104.081968. Epub 2005 Mar 10.
PubMed 15761113
Court MH, Duan SX, von Moltke LL, Greenblatt DJ, Patten CJ, Miners JO, Mackenzie PI. Interindividual variability in acetaminophen glucuronidation by human liver microsomes: identification of relevant acetaminophen UDP-glucuronosyltransferase isoforms. J Pharmacol Exp Ther. 2001 Dec;299(3):998-1006.
PubMed 11714888
Volak LP, Hanley MJ, Masse G, Hazarika S, Harmatz JS, Badmaev V, Majeed M, Greenblatt DJ, Court MH. Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers. Br J Clin Pharmacol. 2013 Feb;75(2):450-62. doi: 10.1111/j.1365-2125.2012.04364.x.
PubMed 22725836
Court MH, Freytsis M, Wang X, Peter I, Guillemette C, Hazarika S, Duan SX, Greenblatt DJ, Lee WM; Acute Liver Failure Study Group. The UDP-glucuronosyltransferase (UGT) 1A polymorphism c.2042C>G (rs8330) is associated with increased human liver acetaminophen glucuronidation, increased UGT1A exon 5a/5b splice variant mRNA ratio, and decreased risk of unintentional acetaminophen-induced acute liver failure. J Pharmacol Exp Ther. 2013 May;345(2):297-307. doi: 10.1124/jpet.112.202010. Epub 2013 Feb 13.
PubMed 23408116
Court MH, Peter I, Hazarika S, Vasiadi M, Greenblatt DJ, Lee WM; Acute Liver Failure Study Group. Candidate gene polymorphisms in patients with acetaminophen-induced acute liver failure. Drug Metab Dispos. 2014 Jan;42(1):28-32. doi: 10.1124/dmd.113.053546. Epub 2013 Oct 8.
PubMed 24104197
Zhao Y, Harmatz JS, Epstein CR, Nakagawa Y, Kurosaki C, Nakamura T, Kadota T, Giesing D, Court MH, Greenblatt DJ. Favipiravir inhibits acetaminophen sulfate formation but minimally affects systemic pharmacokinetics of acetaminophen. Br J Clin Pharmacol. 2015 Nov;80(5):1076-85. doi: 10.1111/bcp.12644. Epub 2015 Jun 8.
PubMed 25808818
Papageorgiou I, Freytsis M, Court MH. Transcriptome association analysis identifies miR-375 as a major determinant of variable acetaminophen glucuronidation by human liver. Biochem Pharmacol. 2016 Oct 1;117:78-87. doi: 10.1016/j.bcp.2016.08.014. Epub 2016 Aug 13.
PubMed 27531059
Papageorgiou I, Court MH. Identification and validation of microRNAs directly regulating the UDP-glucuronosyltransferase 1A subfamily enzymes by a functional genomics approach. Biochem Pharmacol. 2017 Aug 1;137:93-106. doi: 10.1016/j.bcp.2017.04.017. Epub 2017 Apr 19.
PubMed 28433553
Court MH, Zhu Z, Masse G, Duan SX, James LP, Harmatz JS, Greenblatt DJ. Race, Gender, and Genetic Polymorphism Contribute to Variability in Acetaminophen Pharmacokinetics, Metabolism, and Protein-Adduct Concentrations in Healthy African-American and European-American Volunteers. J Pharmacol Exp Ther. 2017 Sep;362(3):431-440. doi: 10.1124/jpet.117.242107. Epub 2017 Jun 29.
PubMed 28663312

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Recruiting
Empowered Relief® for Cancer Survivors With Chronic Pain
Chronic Pain Due to Cancer, Pain Catastrophizing
RecruitingPhase 4
ESP Blocks for Posterior Spinal Fusion
Postoperative Pain
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruiting
Effects of Hip Hinge Exercises on Pain, Range of Motion and Functional Disability in Non-specific Low Back Pain.
Low Back Pain

All Pain trials

Study at a glance

From the registry record, last updated by the sponsor on 23 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics
ClinicalTrials.gov ID: NCT00768716
Acronym / sponsor ID: 8600
Conditions: Pain, Fever, Hepatotoxicity
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 95 participants (actual)
Lead sponsor: Tufts UniversityUniversity, hospital or other
Collaborators: National Institute of General Medical Sciences (NIGMS)
Study start: Dec 2008 (actual)
Primary completion: Jun 2012 (actual)
Study completion: Dec 2013 (actual)
First posted: 8 Oct 2008 (estimated)
Results: Posted 8 May 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
White subjects	Experimental	Drug: Acetaminophen2 x 500 mg acetaminophen by mouth once
Black subjects	Experimental	Drug: Acetaminophen2 x 500 mg acetaminophen by mouth once

Who may qualify

Ages: 18 to 64 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

self-declared white/Caucasian
self-declared African-American
active
ambulatory
no evidence of medical disease

Key exclusion criteria (11 listed)

alcohol use of 3 or more drinks per day
HIV or hepatitis (B or C) infection
isoniazid
disulfiram
phenobarbital

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: Tylenol2 x 500 mg by mouth once	Drug	Black subjects, White subjects

Primary outcome

Acetaminophen Plasma Clearance Association With Race/Ethnicity
Time frame: 2 days
Plasma total clearance of acetaminophen in plasma measured by HPLC
Acetaminophen Glucuronidation Partial Clearance Association With Race/Ethnicity
Time frame: 2 days
Acetaminophen glucuronidation partial clearance determined from plasma clearance and urinary metabolite excretion
Acetaminophen Sulfation Partial Clearance Association With Race/Ethnicity
Time frame: 2 days
Acetaminophen sulfation partial clearance determined from plasma clearance and urinary metabolite excretion
Acetaminophen Oxidation Partial Clearance Association With Race/Ethnicity
Time frame: 2 days
Acetaminophen oxidation partial clearance determined from plasma clearance and urinary metabolite excretion
Acetaminophen Plasma Clearance Association With UGT2B15 Genotype
Time frame: 2 days
The association of UGT2B15 genotype with acetaminophen total clearance
Acetaminophen Glucuronidation Partial Clearance Association With UGT2B15 Genotype
Time frame: 2 days
The association of acetaminophen glucuronidation partial clearance with UGT2B15 genotype
APAP Plasma Adduct Association With UGT2B15 Genotype
Time frame: 2 days
The association of UGT2B15 genotype with APAP plasma adduct concentrations

Results and safety

Results posted to the registry on 8 May 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
White Subjects	54	54
Black Subjects	41	41

Primary outcome: Acetaminophen Plasma Clearance Association With Race/Ethnicity

Time frame: 2 days. Median (Inter-Quartile Range). Unit: mL/min/kg

Measure	White Subjects n = 54	Black Subjects n = 41
Value	5.3 (4.8 to 6.4)	5.9 (5.1 to 6.9)

White Subjects vs Black Subjects: p = 0.52, Wilcoxon (Mann-Whitney)

Primary outcome: Acetaminophen Glucuronidation Partial Clearance Association With Race/Ethnicity

Time frame: 2 days. Median (Inter-Quartile Range). Unit: mL/min/kg

Measure	White Subjects n = 54	Black Subjects n = 41
Value	2.9 (2.3 to 3.8)	3.3 (2.4 to 4.1)

White Subjects vs Black Subjects: p = 0.42, Wilcoxon (Mann-Whitney)

Primary outcome: Acetaminophen Sulfation Partial Clearance Association With Race/Ethnicity

Time frame: 2 days. Median (Inter-Quartile Range). Unit: mL/min/kg

Measure	White Subjects n = 54	Black Subjects n = 41
Value	1.4 (1.1 to 1.7)	1.7 (1.3 to 2.2)

White Subjects vs Black Subjects: p = 0.06, Wilcoxon (Mann-Whitney)

Primary outcome: Acetaminophen Oxidation Partial Clearance Association With Race/Ethnicity

Time frame: 2 days. Median (Inter-Quartile Range). Unit: mL/min/kg

Measure	White Subjects n = 54	Black Subjects n = 41
Value	0.9 (0.65 to 1.15)	0.57 (0.49 to 0.77)

Adverse events

Time frame: 2 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
White Subjects	0 of 54 (0%)	0 of 54 (0%)	0 of 54
Black Subjects	0 of 41 (0%)	0 of 41 (0%)	0 of 41

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 15761114Krishnaswamy S, Hao Q, Al-Rohaimi A, Hesse LM, von Moltke LL, Greenblatt DJ, Court MH. UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: I. Identification of polymorphisms in the 5'-regulatory and exon 1 regions, and association with human liver UGT1A6 gene expression and glucuronidation. J Pharmacol Exp Ther. 2005 Jun;313(3):1331-9. doi: 10.1124/jpet.104.081950. Epub 2005 Mar 10.
Background: PubMed 15761113Krishnaswamy S, Hao Q, Al-Rohaimi A, Hesse LM, von Moltke LL, Greenblatt DJ, Court MH. UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: II. Functional impact of the three most common nonsynonymous UGT1A6 polymorphisms (S7A, T181A, and R184S). J Pharmacol Exp Ther. 2005 Jun;313(3):1340-6. doi: 10.1124/jpet.104.081968. Epub 2005 Mar 10.
Background: PubMed 11714888Court MH, Duan SX, von Moltke LL, Greenblatt DJ, Patten CJ, Miners JO, Mackenzie PI. Interindividual variability in acetaminophen glucuronidation by human liver microsomes: identification of relevant acetaminophen UDP-glucuronosyltransferase isoforms. J Pharmacol Exp Ther. 2001 Dec;299(3):998-1006.
Background: PubMed 22725836Volak LP, Hanley MJ, Masse G, Hazarika S, Harmatz JS, Badmaev V, Majeed M, Greenblatt DJ, Court MH. Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers. Br J Clin Pharmacol. 2013 Feb;75(2):450-62. doi: 10.1111/j.1365-2125.2012.04364.x.
Background: PubMed 23408116Court MH, Freytsis M, Wang X, Peter I, Guillemette C, Hazarika S, Duan SX, Greenblatt DJ, Lee WM; Acute Liver Failure Study Group. The UDP-glucuronosyltransferase (UGT) 1A polymorphism c.2042C>G (rs8330) is associated with increased human liver acetaminophen glucuronidation, increased UGT1A exon 5a/5b splice variant mRNA ratio, and decreased risk of unintentional acetaminophen-induced acute liver failure. J Pharmacol Exp Ther. 2013 May;345(2):297-307. doi: 10.1124/jpet.112.202010. Epub 2013 Feb 13.
Background: PubMed 24104197Court MH, Peter I, Hazarika S, Vasiadi M, Greenblatt DJ, Lee WM; Acute Liver Failure Study Group. Candidate gene polymorphisms in patients with acetaminophen-induced acute liver failure. Drug Metab Dispos. 2014 Jan;42(1):28-32. doi: 10.1124/dmd.113.053546. Epub 2013 Oct 8.
Background: PubMed 25808818Zhao Y, Harmatz JS, Epstein CR, Nakagawa Y, Kurosaki C, Nakamura T, Kadota T, Giesing D, Court MH, Greenblatt DJ. Favipiravir inhibits acetaminophen sulfate formation but minimally affects systemic pharmacokinetics of acetaminophen. Br J Clin Pharmacol. 2015 Nov;80(5):1076-85. doi: 10.1111/bcp.12644. Epub 2015 Jun 8.
Background: PubMed 27531059Papageorgiou I, Freytsis M, Court MH. Transcriptome association analysis identifies miR-375 as a major determinant of variable acetaminophen glucuronidation by human liver. Biochem Pharmacol. 2016 Oct 1;117:78-87. doi: 10.1016/j.bcp.2016.08.014. Epub 2016 Aug 13.
Background: PubMed 28433553Papageorgiou I, Court MH. Identification and validation of microRNAs directly regulating the UDP-glucuronosyltransferase 1A subfamily enzymes by a functional genomics approach. Biochem Pharmacol. 2017 Aug 1;137:93-106. doi: 10.1016/j.bcp.2017.04.017. Epub 2017 Apr 19.
Results publication: PubMed 28663312Court MH, Zhu Z, Masse G, Duan SX, James LP, Harmatz JS, Greenblatt DJ. Race, Gender, and Genetic Polymorphism Contribute to Variability in Acetaminophen Pharmacokinetics, Metabolism, and Protein-Adduct Concentrations in Healthy African-American and European-American Volunteers. J Pharmacol Exp Ther. 2017 Sep;362(3):431-440. doi: 10.1124/jpet.117.242107. Epub 2017 Jun 29.

Related trials for Pain

Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Recruiting
Empowered Relief® for Cancer Survivors With Chronic Pain
Chronic Pain Due to Cancer, Pain Catastrophizing
RecruitingPhase 4
ESP Blocks for Posterior Spinal Fusion
Postoperative Pain
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruiting
Effects of Hip Hinge Exercises on Pain, Range of Motion and Functional Disability in Non-specific Low Back Pain.
Low Back Pain

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.

Michael H Court, BVSc, PhD principal investigator

Tufts University

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 Pain and Fever, run by Tufts University 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 5 inclusion and 11 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: finished, as of the sponsor's last update on 23 May 2019. 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?

Yes. Results are posted in the registry (first posted 8 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Acetaminophen Plasma Clearance Association With Race/Ethnicity (time frame: 2 days). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00768716, which also lists 10 linked publications.

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 23 May 2019.