Analysis of Volatile Organic Compounds in Expired Air in Healthy Volunteers: Comparison of Three Mass Spectrometry Techniques for the Characterization of Volatolome in Clinical Studies (VOC-COMPARE)

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ClinicalTrials.gov Identifier: NCT06020521

Recruitment Status : Recruiting

First Posted : August 31, 2023

Last Update Posted : September 5, 2023

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Sponsor:

Information provided by (Responsible Party):

Hopital Foch

Study Description

Brief Summary:

A major obstacle in precision medicine is the unavailability of biomarkers that are easy to access, non-invasive, measurable with high-performance techniques, fast, easy to use, reproducible, inexpensive and easily deployable on a large scale. The analysis of exhaled air (volatolomics) is an "omics" approach devoted to the analysis of volatile organic compounds (VOCs) eliminated by the pulmonary route with real-time detection, at the patient's bedside. The reference technology for the analysis of VOCs is mass spectrometry (MS). Several types of mass spectrometers can be used, and, in the absence of a consensual and standardized method, have practical methods for carrying out different analyzes which also lead to the generation of specific signals whose nature, complexity and exhaustiveness of information generated are heterogeneous. The clinical studies carried out to date use one of the analytical techniques available, without the choice necessarily being guided by objective factors. The objective of this study is to fill this gap and compare the information obtained by three mass spectrometry techniques available to our team (proton transfer reaction - mass spectrometry (PTR-MS), Soft Ionization by Chemical Reaction in Transfer (SICRIT) , two-dimensional gas chromatography-mass spectrometry (GCxGC-MS)) for volatolome analysis. The comparative analysis of the different signals will make it possible to determine the interests and limits of each technique and thus to direct preferentially towards one, the other, or combinations of them for the realization of future clinical studies. One of the main challenges also consists in establishing the concordance of the signals generated by the different technological approaches, some employing prior chromatographic separation, others not, and some employing soft ionization methods while those of others are on the contrary hard. Thus, the availability of datasets obtained on the same population with these complementary approaches will allow significant progress for the identification of the COVs of interest in clinical studies, beyond the simple comparison of the analytical performances of the different methods.

Condition or disease	Intervention/treatment	Phase
Respiratory Disease	Other: Three spectrometry differents technics	Not Applicable

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Detailed Description:

Precision medicine, or personalized medicine or individualized medicine, represents an important source of hope for alleviating the social and economic burden of severe pathologies. There is no commonly accepted definition of the notion of "personalized medicine". However, according to the European Council, personalized medicine is a medical model that relies on the characterization of people's phenotypes and genotypes (e.g. through molecular profiling, medical imaging, lifestyle information) to offer the right therapeutic strategy to the right person at the right time and/or to establish the existence of a predisposition to a disease and/or to ensure targeted and timely prevention. Personalized medicine is linked to the broader notion of "patient-centred care", which takes into account the general need for health systems to better meet the needs of patients. Advances in research have made it possible to develop "omic" signatures of therapeutic responses to certain cancers or rare diseases. However, if a few omic or cellular biomarkers have been developed, they remain today insufficient and too complex to foresee their generalization for the individualized treatment of patients. Thus, today there is significant potential for the development of precision medicine for severe pathologies. A major obstacle in precision medicine is the unavailability of biomarkers that are easy to access, non-invasive, measurable with high-performance techniques, fast, easy to use, reproducible, inexpensive and easily deployable on a large scale.

The analysis of exhaled air (volatolomics) is derived from the latest "omics" technology, metabolomics, devoted to the analysis of small molecules in the body, and allows real-time detection, sick bed, volatile organic compounds (VOCs) eliminated through the lungs. Thousands of VOCs have been identified in exhaled air following infectious, inflammatory or pathological events with examples in the field of infectious diseases for the diagnosis of tuberculosis, invasive fungal infections, bacterial colonization of the airways or ventilator-associated pneumonia in intensive care patients . For viral infections, animal models of influenza infections and clinical studies in patients with chronic obstructive pulmonary disease also suggest the benefit of VOC analysis . In this infectious context, the "respiratory fingerprint" detected reflects a mixture of metabolites of microbial origin, direct biomarkers of the presence of pathogenic agents, and metabolites generated by the host in response to the infection. Thus, the analysis of exhaled air, the main advantages of which are totally non-invasive sampling and the instantaneous analysis allowed by certain technologies (result in a few minutes) could be used for diagnosis, large-scale screening, surveillance of infections and prediction of response to treatment. The technological challenges for its realization are linked to the great chemical diversity of the VOCs to be studied and the particularly low abundance of many of them.

The reference technology for the analysis of VOCs is mass spectrometry (MS), which uses instruments consisting of - an ionization source whose function is to ionize the VOCs contained in exhaled air, - an analyzer which sorts the ions formed according to their mass to charge ratio (m/z) and - a detector which allows the quantitative analysis of the m/z signals of a sample . Several types of mass spectrometers can be used, and, in the absence of a consensual and standardized method, have practical methods for carrying out different analyzes which also lead to the generation of signals specific to each of them, the nature, the complexity and the completeness of the information contained being heterogeneous. Each type of instrument has advantages and disadvantages in terms of ease of sampling, speed of analysis, completeness of information and technical and analytical constraints for carrying out the analyses. For example, some instruments such as proton transfer reaction mass spectrometers (PTR-MS) or those using soft ionization by chemical transfer reaction (SICRIT) are relevant for perform measurements online and in real time, without storing a sample of exhaled air but vary by their mode of ionization and the resolution of the associated detectors. However, their level of information generated does not generally allow VOCs to be identified (soft ionization, absence of chromatographic separation, etc.). Indeed, once a signature of VOCs (characterized by their m/z) is discovered, their formal chemical identification is then the critical and obligatory step to improve knowledge on the physiology and regulatory processes of VOCs as well as to set up and clinically validate specific quantitative measurement methods based on portable technologies (sensors, etc.). Two-dimensional gas chromatography coupled with mass spectrometry (GCxGC-MS) is the most advanced technology at present for this purpose, combining two chromatographic columns with complementary stationary phases and ionization of VOCs by electron impact before MS detection. Compounds coeluting in conventional gas chromatography can be separated by GCxGC, and several teams have published proof-of-concept studies using GCxGC-MS for breath biomarker discovery for lung cancer diagnosis , tuberculosis or severe asthma phenotyping . One of the main challenges consists in establishing the concordance of the signals generated by the different technological approaches, some employing a preliminary chromatographic separation, others not, and some employing soft ionization methods whereas those of the others are on the contrary hard. Thus, the availability of datasets obtained on the same population with these complementary technological approaches will allow significant progress for the identification of the COVs of interest in clinical studies, beyond the simple comparison of the analytical performances of the different methods.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	40 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Intervention Model Description:	This research will take place at the hospital and at the UFR Simone Veil-Santé with single sessions on the same day of approximately 10 minutes and 1 hour respectively. A list of healthy volunteers has already been established at the faculty. A provisional schedule for passing the various examinations provided for in the protocol is also scheduled. The experiments conducted at the UFR Simone Veil - Santé will take place within the Department of Health Biotechnology. This Department already has all the resources necessary for the successful completion of the study, in particular within the mass spectrometry platform which has the instruments (high resolution mass spectrometer Q-Exactive) and human resources (2 analytical science engineers, 1 data science engineer + technical staff and interns) required.
Masking:	None (Open Label)
Primary Purpose:	Health Services Research
Official Title:	Analysis of Volatile Organic Compounds in Expired Air in Healthy Volunteers: Comparison of Three Mass Spectrometry Techniques for the Characterization of Volatolome in Clinical Studies
Actual Study Start Date :	July 8, 2023
Estimated Primary Completion Date :	September 30, 2023
Estimated Study Completion Date :	December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Group of healthy volunteers This research will take place at the hospital and at the UFR Simone Veil-Santé with single sessions on the same day of approximately 10 minutes and 1 hour respectively. A list of healthy volunteers has already been established at the faculty. A provisional schedule for passing the various examinations provided for in the protocol is also scheduled. The experiments conducted at the UFR Simone Veil - Santé will take place within the Department of Health Biotechnology. This Department already has all the resources necessary for the successful completion of the study, in particular within the mass spectrometry platform which has the instruments (high resolution mass spectrometer Q-Exactive) and human resources (2 analytical science engineers, 1 data science engineer + technical staff and interns) required.	Other: Three spectrometry differents technics Collection of expired air as follows: For online mass spectrometry techniques (PTR-MS and SICRIT) For offline mass spectrometry (GCxGC-MS) Performing volatolome analyses: By PTR-TOF-MS (Ionicon) and SICRIT-HRMS (SICRIT module (Plasmion) coupled to a Q-exactive instrument (Thermofisher)) for online analyzes By two-dimensional gas chromatography coupled with mass spectrometry (Pegasus BT-4D, Leco) for the desorption tubes.

Arm

Intervention/treatment

Group of healthy volunteers

This research will take place at the hospital and at the UFR Simone Veil-Santé with single sessions on the same day of approximately 10 minutes and 1 hour respectively. A list of healthy volunteers has already been established at the faculty. A provisional schedule for passing the various examinations provided for in the protocol is also scheduled. The experiments conducted at the UFR Simone Veil - Santé will take place within the Department of Health Biotechnology. This Department already has all the resources necessary for the successful completion of the study, in particular within the mass spectrometry platform which has the instruments (high resolution mass spectrometer Q-Exactive) and human resources (2 analytical science engineers, 1 data science engineer + technical staff and interns) required.

Other: Three spectrometry differents technics

Collection of expired air as follows:

For online mass spectrometry techniques (PTR-MS and SICRIT)
For offline mass spectrometry (GCxGC-MS)

Performing volatolome analyses:

By PTR-TOF-MS (Ionicon) and SICRIT-HRMS (SICRIT module (Plasmion) coupled to a Q-exactive instrument (Thermofisher)) for online analyzes
By two-dimensional gas chromatography coupled with mass spectrometry (Pegasus BT-4D, Leco) for the desorption tubes.

Outcome Measures

Primary Outcome Measures :

To compare informations obtained by three different spectrometry techniques [ Time Frame: one day ]
Compare the information obtained by three mass spectrometry techniques (PTR-MS, SICRIT, GCxGC-MS) for the analysis of volatolome during clinical studies

Secondary Outcome Measures :

1- Compare sampling techniques [ Time Frame: one day ]
Compare the information obtained by three mass spectrometry techniques (PTR-MS, SICRIT, GCxGC-MS) for the analysis of volatolome during clinical studies
2-Compare the profile of VOCs [ Time Frame: one day ]
Compare the profile of VOCs of differents patients
Determine the average time needed to perform each type of sample and associated analyzes [ Time Frame: one day ]
Determine the average time needed to perform each type of sample and associated analyzes

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 70 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy volunteer
At least 18 years old
Perfect command of the French language
Signature of an informed consent form
Affiliated to a health insurance plan

Exclusion Criteria:

Pregnant women
People with known pathology(ies)
Active smoking
Deprived of liberty or under guardianship

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06020521

Contacts

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Contact: Stanislas Grassin delyle, PR	01 46 25 73 93	s.grassindelyle@hopital-foch.com
Contact: DRCI promotion	01 46 25 36 42	drci-promotion@hopital-foch.com

Locations

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France
Grassin delyle	Recruiting
Suresnes, France, 92150
Contact: Stanislas Grassin delyle, PR 04 46 25 73 93 s.grassindelyle@hopital-foch.com
Contact: DRCI PROMOTION 01 46 25 36 42 drci-promotion@hopital-foch.com

Sponsors and Collaborators

Hopital Foch

More Information

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Responsible Party:	Hopital Foch
ClinicalTrials.gov Identifier:	NCT06020521
Other Study ID Numbers:	2023_0020
First Posted:	August 31, 2023 Key Record Dates
Last Update Posted:	September 5, 2023
Last Verified:	August 2023

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Hopital Foch:


precision medicine, biomarkers analysis of exhaled air (volatolomics) mass spectrometry

Additional relevant MeSH terms:

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Respiratory Tract Diseases Respiration Disorders

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