Ultralow Dose PAH Binary Mixture Study

Environmental Exposure Clinical Trial

Official title:

Ultralow Dose PAH Binary Mixture Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03631667
• Other study ID #: LPI-8554
• Secondary ID: R01ES028600
• Status: Completed
• Phase: Early Phase 1
• Start date: October 1, 2018
• Est. completion date: February 1, 2024

Study information

• Verified date: February 2024
• Source: Oregon State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: February 1, 2024
• Est. primary completion date: January 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Environmental Exposure

Intervention

Drug:
• [14C]-benzo[a]pyrene
Oral micro-dose (50 ng) (5.4 nCi)
• [14C]-benzo[a]pyrene plus phenanthrene
Oral micro-dose of 50 ng (5.4 nCi) [14C]-benzo[a]pyrene plus 1250 ng phenanthrene

Locations

Country	Name	City	State
United States	Oregon State University	Corvallis	Oregon

Sponsors (4)

Lead Sponsor	Collaborator
Oregon State University	Lawrence Livermore National Laboratory, National Institute of Environmental Health Sciences (NIEHS), Pacific Northwest National Laboratory

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma and urine 14C-BaP and 14C-BaP metabolite levels after oral dose	Plasma and urine levels of 14C-BaP and 14C-BaP metabolites measured by accelerator mass spectrometry	48 hours
Secondary	Peak plasma concentration of 14C-BaP Cmax	Determination of highest concentration of 14C-BaP in plasma	48 hours
Secondary	Time at highest plasma concentration of 14C-BaP Tmax	Determination of time at which plasma concentration of 14C-BaP is highest	48 hours
Secondary	Area under plasma concentration of 14C-BaP versus time curve AUC	Integration of concentration of 14C-BaP in plasma over time	48 hours
Secondary	Rate of elimination of 14C-BaP	Determination of constants for rate of elimination of 14C-BaP from plasma	48 hours
Secondary	Metabolites of 14C-BaP in plasma	Determination of plasma metabolites of 14C-BaP	48 hours
Secondary	Metabolites of 14C-BaP in urine	Determination of urinary metabolites of 14C-BaP	48 hours