Benzo[a]Pyrene Ultralow Dose-Response Study

NCT ID: NCT03318978

Last Updated: 2025-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-17
• Study Completion Date: 2024-02-01

Brief Summary

Evaluation of the pharmacokinetics for [14C]-benzo[a]pyrene ([14C]-BaP) and metabolites in plasma and urine over 48 hours following 4 oral doses of 25, 50, 10 and 250 ng (2.7-27 nCi).

Detailed Description

The pharmacokinetics for [14C]-BaP and metabolites will be assessed by UHLPC-Accelerator Mass Spectrometry (AMS, Lawrence Livermore National Laboratory) in plasma and urine collected over 48 hours following oral doses of 25, 50, 100 or 250 ng (2.7-27 nCi). Metabolite profiles and kinetics of elimination over this dose range are predicted to be consistent with a BaP physiologically based pharmacokinetic (PBPK) model developed by Pacific Northwest National Laboratory (PNNL). A non-smoker, not exposed occupationally, receives 270-700 ng of BaP daily; about 95% dietary. The WHO has set an estimated safe daily lifetime (70 year/70 Kg individual, cancer endpoint) exposure to BaP of 42-350 ng. This protocol represents de minimus risk.

Conditions

Environmental Exposure

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

25 ng dose, 50 ng dose, 100 ng dose, 250 ng dose

Cycle 1: Capsule containing 25 ng (2.7 nCi) [14C]-benzo[a]pyrene (BaP).

Cycle 2: Capsule containing 50 ng (2.7 nCi) [14C]-benzo[a]pyrene (BaP).

Cycle 3: Capsule containing 100 ng (2.7 nCi) [14C]-benzo[a]pyrene (BaP).

Cycle 4: Capsule containing 250 ng (2.7 nCi) [14C]-benzo[a]pyrene (BaP).

At least 3 weeks will pass between cycles as a washout period.

Group Type: EXPERIMENTAL

[14C]-benzo[a]pyrene

Intervention Type: DRUG

Oral micro-dose range (25, 50, 100 and 250 ng)

Interventions

[14C]-benzo[a]pyrene

Oral micro-dose range (25, 50, 100 and 250 ng)

Intervention Type: DRUG

Other Intervention Names

Carcinogenic PAH environmental pollutant

Eligibility Criteria

Inclusion Criteria

• Age 21-65 (inclusive)
• Must be post-menopausal or have had surgical sterilization to eliminate any possibility for fetal exposure
• Willing to defer blood donation for one month before, throughout, and one month after completion of study activities
• Willing to avoid consuming cruciferous vegetables, I3C or DIM supplements, smoked or cured meat or cheeses, or charcoal-grilled meats for 2 weeks prior to and during each study cycle (gas grilled foods acceptable)

• Age 21-65 (inclusive)
• Willing to defer blood donation for one month before, throughout, and one month after completion of study activities
• Willing to avoid consuming cruciferous vegetables, I3C or DIM supplements, smoked or cured meat or cheeses, or charcoal-grilled meats for 2 weeks prior to and during each study cycle (gas grilled foods acceptable)

Exclusion Criteria

• Smoker (tobacco or other substances) or use of smokeless tobacco in past 3 months or living with smoker
• Regular use of medications that affect gut motility or nutrient absorption (e.g. cholestyramine, sucralfate, orlistat, pro- or anti-motility agents)
• History of gastrointestinal surgery (e.g. bariatric surgery, cholecystectomy) or gastrointestinal disorder (Crohn's disease, celiac disease, IBS, or colitis)
• Current or history of kidney or liver disease
• Prior high-dose 14C exposure from medical tests. (micro-dose 14C exposure not exclusionary)
• Occupational PAH exposure (e.g. roofers, asphalt pavers, fire-fighters, etc.)

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Environmental Health Sciences (NIEHS)

NIH

Sponsor Role: collaborator

Lawrence Livermore National Laboratory

OTHER

Sponsor Role: collaborator

Pacific Northwest National Laboratory

FED

Sponsor Role: collaborator

Oregon State University

OTHER

Sponsor Role: lead

Responsible Party

David Williams

Helen P. Rumbel Professor for Cancer Prevention

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Clinical Research Facility, 407 Linus Pauling Science Center, Oregon State University

Corvallis, Oregon, United States

Countries

United States

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

R01ES028600

Identifier Type: NIH

Identifier Source: secondary_id

View Link

LPI-8233

Identifier Type: -

Identifier Source: org_study_id