Biological Signatures Resulting From Occupational Exposure to Complex Mixtures of PAHs (PAH-ProMetGen)

May 31, 2024 updated by: University Hospital, Grenoble

Biological Signatures (Proteomics, Metabolomics and Genotoxicity) Associated With Occupational Exposure to PAH Mixtures and Relation With Exposure Biomarkers: Support for the Derivation of Biological Limit Values

This research project aims at better understanding the early biological effects resulting from occupational exposure to complex Polycyclic Aromatic Hydrocarbon (PAH) mixtures.

Current biomarkers used as part of biomonitoring campaigns are biomarkers of exposure, not numerous and poorly related to health effects.

The aim of this study is thus to improve our understanding of biological consequences of such exposures, both in terms of proteins deregulation, metabolism deregulation and genotoxicity.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PAHs are ubiquitous pollutants inducing several diseases, among which cancer is the most significant endpoint, with increased incidences of lung, skin, and bladder cancers. PAHs induce genotoxic effects (sister chromatids exchange, micronuclei, DNA damage) but require metabolic activation in humans as indirect-acting carcinogens. Thus, the knowledge of metabolic pathways involved following PAH exposure is critical for understanding and preventing cancer risks. Besides, exposure to PAHs is assumed to induce other adverse health effects (diabetes, inflammation, infertility, cardiovascular disease). Unfortunately, early disease-related biomarkers are still largely unknown and our comprehension about the mechanisms involved is still limited. The rare existing biological limit values either refer to not carcinogenic PAH (pyrene) or detoxification pathways (3-OHBaP for BaP), although new biomarkers reflecting the genotoxic pathway of BaP (TetraolBaP) are now available. There is thus a need for identifying more relevant biomarkers of exposure / effect, and for a better understanding of the biological consequences resulting from PAH exposures as well as the associated metabolic pathways involved.

The objectives of the project are :

  • To better understand and characterize molecular, metabolic and genotoxic impacts resulting from exposure to PAHs and to link such impacts with biological levels of various PAH metabolites,
  • To study the influence of BaP metabolism (genotoxic versus detoxication pathway) on the differential expression of metabolites / proteins and on genotoxicity endpoints in order to get relevant data for deriving new biological limit values,
  • To elucidate the associations between omics deregulations due to PAH exposures and activated metabolic pathways, in order to define candidate effect biomarkers for human biomonitoring.

The originalities of the project are the following. First, this is a human study performed in real occupational settings on workers exposed to representative PAH mixtures. It is a multidisciplinary approach simultaneously combining up-to-date biomonitoring, omics and cytogenetics analyses, that will give insight into a comprehensive view of metabolic reactions and protein expressions following occupational exposure to PAH mixtures, and allow the identification of the biological processes involved. Carcinogenic BaP metabolites (Tetraol-BaP and 3-OHBaP) will be simultaneously analyzed in order to compare the two main metabolic pathways of BaP.

The main steps of the projects will be :

  • Recruitment of 100 workers differentially exposed to PAH mixtures sampled across two time periods (after weeks of exposure and following 3 weeks without occupational exposure),
  • Recording of relevant data (work characteristics, jobs / tasks, working experience, number of years of exposure, smoking habits, nutritional intake, co-morbidity),
  • Toxicological analyses (LC-Fluorescence and GC-MS-MS) of urinary metabolites of several gaseous and particulate PAHs (Naphtalene, Fluorene, Phenanthrene, Pyrene, BaP, BeP, Chrysene, Benzo(b)Fluoranthene, Benzo(k)Fluoranthene, Benzo(a)Anthracene),
  • Proteomics analyses on blood samples through an enrichment approach for a bottom-up label free quantitative proteomic analysis based LC-HR-MS. Deregulated proteins (DEP) will be identified and the associated protein signature. A gene ontology (GO) analysis will define the groups of biological processes involved,
  • Untargeted Metabolomics analyses on blood samples in UHPLC-HR-MS, with unsupervised statistical analyses (Principal Component Analysis, Logistic Regressions), identification of relevant metabolites by their comparison to the Human Metabolome database, and advanced molecular networking / spectral library search of LC-MSMS data,
  • Micronuclei (MN) in buccal cells through the harvesting of buccal cells using a cytobrush, transfer to the lab in a buffer, fixing and staining, automatic counting under fluorescent light.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Subjects ages 18 years or more
  • Subjects occupationally exposed to PAHs since more than 3 months
  • Having signed the informed consent
  • recruited by the occupational health service

Exclusion Criteria:

  • Obesity (BMI>30)
  • Subjects suffering cancers or metabolic diseases (diabetes, dyslipidemia, amino-acid diseases, renal or hepatic impairment) at the onset of the study.
  • Subjects taking medications related to the above diseases at the onset of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Subjects occupationally exposed to PAHs
Biological: Characterization of early biological effects following exposure to PAHs
Biological samples collected in period of exposure and after holidays

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Deregulation of blood proteins expression due to exposure to PAHs
Time Frame: up to 6 months between both periods of study
Number of proteins up or down regulated in period of exposure versus after holidays
up to 6 months between both periods of study
Deregulation of blood metabolites expression due to exposure to PAHs
Time Frame: up to 6 months between both periods of study
Number of metabolites up or down regulated in period of exposure versus after holidays
up to 6 months between both periods of study
Frequency of micronuclei measured due to exposure to PAHs
Time Frame: up to 6 months between both periods of study
Frequency of cells containing micronuclei in period of exposure versus after holidays
up to 6 months between both periods of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Grenoble

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Renaud PERSOONS, University Hospital, Grenoble

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 25, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 23, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 23, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 11, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 3, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 31, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 38RC22.0219
  • 2022-A01590-43 (Other Identifier: IDRCB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings