Clinical trial NCT03631667: Ultralow Dose PAH Binary Mixture Study
Official title: Ultralow Dose PAH Binary Mixture Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Environmental Exposure
Keywords: Benzo[a]pyrene
Accelerator Mass Spectrometry
Polycyclic Aromatic Hydrocarbons
Phenanthrene
Lead sponsor: Oregon State University
Sponsor class: OTHER
Collaborators: name: National Institute of Environmental Health Sciences (NIEHS)
name: Lawrence Livermore National Laboratory
name: Pacific Northwest National Laboratory
First posted: 2018-08-15
Enrollment: 8
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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 or with 1250 ng phenanthrene.

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 50 ng dose (5.4 nCi) alone or with 1250 ng phenanthrene. Metabolite profiles and kinetics of elimination 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.

Eligibility criteria: Inclusion Criteria:

* 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)

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.)
* Regular use of indole-3-carbinol or DIM dietary supplements

Primary outcomes:
measure: Peak Plasma Concentration of 14C-BaP Cmax
timeFrame: 0-48 hours for each of 2 dosing cycles, with a washout period of 3 weeks between the dosing cycles
measure: Time at Highest Plasma Concentration of 14C-BaP Tmax
timeFrame: 0-48 hours for each of 2 dosing cycles, with a washout period of 3 weeks between the dosing cycles
Secondary outcomes:
measure: Area Under Plasma Concentration of 14C-BaP Versus Time Curve AUC
timeFrame: 0-48 hours for each of 2 dosing cycles, with a washout period of 3 weeks between the dosing cycles
measure: Rate of Elimination of 14C-BaP (Half Life)
timeFrame: 0-48 hours for each of 2 dosing cycles, with a washout period of 3 weeks between the dosing cycles
Other outcomes:
Locations:
city: Corvallis
country: United States
facility: Oregon State University
state: Oregon
Study officials:
References: