Pharmacokinetics of Benzo[a]Pyrene: Impact of Diet

NCT03802721 | Completed Early Phase 1 Results FDA Drug

• 2 other identifiers: LPI-8789R01ES028600
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluation of the pharmacokinetics for \[14C\]-benzo\[a\]pyrene (\[14C\]-BaP) and metabolites in plasma and urine over 48 hours following a 50 ng dose (5.4 nCi) alone, following 7 days' consumption of Brussels sprouts, and following 7 days' consumption of a supplement containing 3,3'-diindolylmethane (DIM).

Conditions

Environmental Exposure

Keywords

Benzo[a]pyrene; Accelerator Mass Spectrometry; Polycyclic Aromatic Hydrocarbons; cruciferous vegetable; Brussels sprouts; 3,3'-diindolylmethane; DIM; indole-3-carbinol; I3C; PAH

Outcome Measures

Primary Outcomes (1)

• Peak Plasma Concentration of 14C-BaP Cmax

  Determination of highest concentration of 14C-BaP in plasma. Blood samples collected at 0 (baseline), 0.25, 0.5, 1, 2, 3, 4, 8, 24, and 48 hour after dosing. All time points were used to determine Cmax.

  0-48 hours for each of 3 dosing cycles, with a washout period of 3 weeks between each dosing cycle

Secondary Outcomes (3)

• Time at Highest Plasma Concentration of 14C-BaP Tmax

  0-48 hours for each of 3 dosing cycles, with a washout period of 3 weeks between each dosing cycle

• Area Under Plasma Concentration of 14C-BaP Versus Time Curve AUC

  0-48 hours for each of 3 dosing cycles, with a washout period of 3 weeks between each dosing cycle

• Rate of Elimination of 14C-BaP (Half Life)

  0-48 hours for each of 3 dosing cycles, with a washout period of 3 weeks between each dosing cycle

Study Arms (1)

50 ng dose; Brussels sprouts before 50 ng dose; DIM supplement before 50 ng dose

EXPERIMENTAL

Cycle 1: Capsule containing 50 ng (5.4 nCi) \[14C\]-benzo\[a\]pyrene (BaP). Cycle 2: Subjects will consume 50 g (about 1/2 cup) of lightly steamed Brussels sprouts each evening for 7 days prior to taking capsule containing 50 ng (5.4 nCi) \[14C\]-benzo\[a\]pyrene (BaP). Cycle 3: Subjects will consume 300 mg DIM supplement ( 2 capsules of BioResponse DIM® 150) each evening for 7 days prior to taking capsule containing 50 ng (5.4 nCi) \[14C\]-benzo\[a\]pyrene (BaP). A 300 mg DIM dose will be co-administrated with the 50 ng BaP dose. At least 3 weeks will pass between cycles as a washout period.

Drug: [14C]-benzo[a]pyrene; Drug: Brussels sprouts before 50 ng dose; Drug: DIM supplement before 50 ng dose

Interventions

[14C]-benzo[a]pyrene DRUG

Oral micro-dose (50 ng) (5.4 nCi)

Also known as: Carcinogenic PAH environmental pollutant

50 ng dose; Brussels sprouts before 50 ng dose; DIM supplement before 50 ng dose

Brussels sprouts before 50 ng dose DRUG

Brussels sprouts for 7 days before 50 ng (5.4 nCi) dose of BaP

Also known as: Brussels sprouts and carcinogenic PAH

50 ng dose; Brussels sprouts before 50 ng dose; DIM supplement before 50 ng dose

DIM supplement before 50 ng dose DRUG

DIM supplement for 7 days before 50 ng (5.4 nCi) dose of BaP and coadministration with DIM supplement

Also known as: Cruciferous vegetable supplement and carcinogenic PAH

50 ng dose; Brussels sprouts before 50 ng dose; DIM supplement before 50 ng dose

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 21-65 (inclusive)
• If female, 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)
• Health history review and physical assessment showing general good health, as determined by study physician. Acceptable physical exam may have been conducted as part of protocol 8233 or 8554 if subject has not had significant changes in health status.

You may not qualify if:

• 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
• Occupational PAH exposure (e.g. roofers, asphalt pavers, fire-fighters, etc.)
• Regular use of indole-3-carbinol or DIM dietary supplements
• Allergy or intolerance to Brussels sprouts or similar foods

Sponsors & Collaborators

• Oregon State University: lead
• National Institute of Environmental Health Sciences (NIEHS): collaborator
• Lawrence Livermore National Laboratory: collaborator
• Pacific Northwest National Laboratory: collaborator

Study Sites (1)

Oregon State University

Corvallis, Oregon, 97331, United States

Location

Results Point of Contact

• Title: David E. Williams, PhD
• Organization: Oregon State University

david.williams@oregonstate.edu

541-737-3277

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Deidentified samples will be analyzed by AMS at Lawrence Livermore National Laboratory and the pharmacokinetics determine at Pacific Northwest National Laboratory.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 10, 2019
• First Posted: January 14, 2019
• Study Start: January 24, 2019
• Primary Completion: January 1, 2024
• Study Completion: February 1, 2024
• Last Updated: June 22, 2025
• Results First Posted: May 9, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)