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Benzo[a]Pyrene Ultralow Dose-Response Study

Sponsor
Oregon State University (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03318978
Collaborator
National Institute of Environmental Health Sciences (NIEHS) (NIH), Lawrence Livermore National Laboratory (Other), Pacific Northwest National Laboratory (U.S. Fed)
8
Enrollment
1
Location
4
Arms
66.5
Anticipated Duration (Months)
0.1
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Early Phase 1

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
8 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
Single (Outcomes Assessor)
Masking Description:
Deidentified samples will be analyzed by AMS at Lawrence Livermore National Laboratory and the pharmacokinetics determine at Pacific Northwest National Laboratory.
Primary Purpose:
Basic Science
Official Title:
Benzo[a]Pyrene Ultralow Dose-Response Study
Actual Study Start Date :
Apr 17, 2018
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Nov 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: 25 ng dose

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

Drug: [14C]-benzo[a]pyrene
Oral micro-dose range (25, 50, 100 and 250 ng)
Other Names:
  • Carcinogenic PAH environmental pollutant

    		•
    Experimental: 50 ng dose

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

    Drug: [14C]-benzo[a]pyrene
    Oral micro-dose range (25, 50, 100 and 250 ng)
    Other Names:
  • Carcinogenic PAH environmental pollutant

    		•
    Experimental: 100 ng dose

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

    Drug: [14C]-benzo[a]pyrene
    Oral micro-dose range (25, 50, 100 and 250 ng)
    Other Names:
  • Carcinogenic PAH environmental pollutant

    		•
    Experimental: 250 ng dose

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

    Drug: [14C]-benzo[a]pyrene
    Oral micro-dose range (25, 50, 100 and 250 ng)
    Other Names:
  • Carcinogenic PAH environmental pollutant

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Plasma and urine benzo[a]pyrene and metabolite levels after oral dose [48 hours]

      Plasma and urine levels measured by accelerator mass spectrometry

    Secondary Outcome Measures

    1. Peak plasma concentration Cmax [48 hours]

      Determination of highest concentration in plasma

    2. Time at highest plasma concentration Tmax [48 hours]

      Determination of time at which plasma concentration is highest

    3. Area under plasma concentration versus time curve AUC [48 hours]

      Integration of concentration over time

    4. Rate of elimination [48 hours]

      Determination of constants for rate of elimination from plasma

    5. Metabolites in plasma [48 hours]

      Determination of plasma metabolites

    6. Metabolites in urine [48 hours]

      Determination of urinary metabolites

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    21 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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.)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clinical Research Facility, 407 Linus Pauling Science Center, Oregon State University Corvallis Oregon United States 97331

    Sponsors and Collaborators

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

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    David Williams, Helen P. Rumbel Professor for Cancer Prevention, Oregon State University
    ClinicalTrials.gov Identifier:
    NCT03318978
    Other Study ID Numbers:
    • LPI-8233
    • R01ES028600
    First Posted:
    Oct 24, 2017
    Last Update Posted:
    Sep 13, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by David Williams, Helen P. Rumbel Professor for Cancer Prevention, Oregon State University
    Benzo[a]pyrene
    Accelerator Mass Spectrometry
    Polycyclic Aromatic Hydrocarbons

    Study Results

    No Results Posted as of Sep 13, 2021