Ignite Creation Date:
2024-05-06 @ 12:37 PM
Last Modification Date:
2024-10-26 @ 1:01 PM
Study NCT ID:
NCT03802721
Status:
COMPLETED
Last Update Posted:
2024-02-15
First Post:
2019-01-10
Brief Title:
Pharmacokinetics of BenzoaPyrene Impact of Diet
Sponsor:
Oregon State University
Organization:
Oregon State University
Study Overview
Official Title:
Pharmacokinetics of BenzoaPyrene Impact of Diet
Status:
COMPLETED
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Evaluation of the pharmacokinetics for 14C-benzoapyrene 14C-BaP and metabolites in plasma and urine over 48 hours following a 50 ng dose 54 nCi alone following 7 days consumption of Brussels sprouts and following 7 days consumption of a supplement containing 33-diindolylmethane DIM
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 54 nCi alone following 7 days consumption of Brussels sprouts and following 7 days consumption of a supplement containing 33-diindolylmethane DIM
The investigators hypothesize that pre-administration of Brussels sprouts or DIM will alter 14C-BaP metabolism and increase the rate of elimination consistent with predictions based on a previously developed Physiologically-Based Pharmacokinetic PBPK model for BaP Briefly this hypothesis will be tested by dosing individuals with 50 ng 14C-BaP alone and following a 3-week washout period ingestion of about 50 g Brussels sprouts or 300 mg of 33-diindolylmethane DIM supplement for 7 days prior to the 14C-BaP micro-dose The impact of the supplement and the whole food will be assessed with respect to alterations in uptake from the GI tract metabolism and rate of elimination The consumption of cruciferous vegetables will be assessed at the beginning of the study by completion of a dietary questionnaire to examine typical eating patterns in the previous 3 months and by collection and extraction of blood and urine to assay for DIM by LCESI-MSMS-SRM In addition for each phase urine will be assayed for DIM as an estimate of crucifer or DIM supplement intake
In preclinical and clinical studies administration of Brussels sprouts or DIM impacts the activity of the same enzymes responsible for the phase 1 CYP1A1 and CYP1B1 and phase 2 enzymes GSTM1 UGT SULT Monitoring changes in β-estradiol metabolites will confirm the mechanism of alteration in the metabolic profile of 14C-BaP
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 year70 Kg individual cancer endpoint exposure to BaP of 42-350 ng This protocol represents de minimus risk
The investigators hypothesize that pre-administration of Brussels sprouts or DIM will alter 14C-BaP metabolism and increase the rate of elimination consistent with predictions based on a previously developed Physiologically-Based Pharmacokinetic PBPK model for BaP Briefly this hypothesis will be tested by dosing individuals with 50 ng 14C-BaP alone and following a 3-week washout period ingestion of about 50 g Brussels sprouts or 300 mg of 33-diindolylmethane DIM supplement for 7 days prior to the 14C-BaP micro-dose The impact of the supplement and the whole food will be assessed with respect to alterations in uptake from the GI tract metabolism and rate of elimination The consumption of cruciferous vegetables will be assessed at the beginning of the study by completion of a dietary questionnaire to examine typical eating patterns in the previous 3 months and by collection and extraction of blood and urine to assay for DIM by LCESI-MSMS-SRM In addition for each phase urine will be assayed for DIM as an estimate of crucifer or DIM supplement intake
In preclinical and clinical studies administration of Brussels sprouts or DIM impacts the activity of the same enzymes responsible for the phase 1 CYP1A1 and CYP1B1 and phase 2 enzymes GSTM1 UGT SULT Monitoring changes in β-estradiol metabolites will confirm the mechanism of alteration in the metabolic profile of 14C-BaP
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 year70 Kg individual cancer endpoint exposure to BaP of 42-350 ng This protocol represents de minimus risk
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01ES028600 | NIH | None | httpsreporternihgovquickSearchR01ES028600 |