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)
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Suresnes, France, 92150
- Grassin delyle
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Health Services Research
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Other: 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.
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Collection of expired air as follows:
Performing volatolome analyses:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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To compare informations obtained by three different spectrometry techniques
Time Frame: one day
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Compare the information obtained by three mass spectrometry techniques (PTR-MS, SICRIT, GCxGC-MS) for the analysis of volatolome during clinical studies
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one day
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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1- Compare sampling techniques
Time Frame: one day
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Compare the information obtained by three mass spectrometry techniques (PTR-MS, SICRIT, GCxGC-MS) for the analysis of volatolome during clinical studies
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one day
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2-Compare the profile of VOCs
Time Frame: one day
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Compare the profile of VOCs of differents patients
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one day
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Determine the average time needed to perform each type of sample and associated analyzes
Time Frame: one day
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Determine the average time needed to perform each type of sample and associated analyzes
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one day
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2023_0020
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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