Clinical trial NCT03318978: Benzo[a]Pyrene Ultralow Dose-Response Study
Official title: Benzo[a]Pyrene Ultralow Dose-Response Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Environmental Exposure
Keywords: Benzo[a]pyrene
Accelerator Mass Spectrometry
Polycyclic Aromatic Hydrocarbons
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: 2017-10-24
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 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.

Eligibility criteria: Inclusion Criteria:

* Inclusion criteria for women:

  * 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)

Inclusion criteria for men:

* 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:

Exclusion criteria for both men and women:

* 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.)

Primary outcomes:
measure: Peak Plasma Concentration Cmax
timeFrame: 0-48 hours for each of the 4 dosing cycles with a washout period of 3 weeks between each dosing cycle
Secondary outcomes:
measure: Time at Highest Plasma Concentration Tmax
timeFrame: 0-48 hours for each of the 4 dosing cycles with a washout period of 3 weeks between each dosing cycle
measure: Area Under Plasma Concentration Versus Time Curve AUC
timeFrame: 0-48 hours for each of the 4 dosing cycles with a washout period of 3 weeks between each dosing cycle
measure: Rate of Elimination (k1e)
timeFrame: 0-48 hours for each of the 4 dosing cycles with a washout period of 3 weeks between each dosing cycle
Other outcomes:
Locations:
city: Corvallis
country: United States
facility: Clinical Research Facility, 407 Linus Pauling Science Center, Oregon State University
state: Oregon
Study officials:
References: