Evaluating the VOCORDER device for early disease detection through breath analysis: study protocol for a two-phase clinical study.

INTRODUCTION: The survival rate of patients with life-threatening diseases primarily depends on the speed of diagnosis. Too often, diseases are detected only after symptoms appear, which usually occurs at later stages of a disease when available treatments may be less effective. Current detection techniques primarily depend on identifying metabolites in biofluids such as blood and urine. The analysis of these fluids is typically performed in laboratories, resulting in lengthy waiting times for patients to receive their results. In severe cases, invasive biopsies and radiative methods are used to diagnose conditions such as cancer. These biopsies can cause distress for patients who are already experiencing significant emotional or physical stress, while imaging techniques involving ionising radiation may pose additional health risks. Additionally, these methods can be costly. In recent years, exhaled breath has become a biofluid matrix of interest for disease detection, allowing for the identification of volatile organic compounds (VOCs) or VOC profiles associated with specific conditions. To improve early disease detection through breath analysis, the VOCORDER project aims to develop a device that provides a fast, simple, user-friendly and cost-effective method for continuous health monitoring to identify diseases in their early stages before symptoms appear. METHODS AND ANALYSES: A literature review was initially conducted to identify five reference diseases of interest (lung cancer, stomach/colon cancer, breast cancer and kidney insufficiency) and previously reported VOC profiles associated with these diseases. In this trial, the project team from the MITERA Hospital will select patients, and the hospital staff will conduct personal interviews with these subjects. Each participant will also complete a questionnaire for the acquisition of demographic and medical history data, after being informed in detail about the purposes of the questionnaire and signing a consent form. The study protocol consists of two phases. Phase 1 is a baseline study designed to detect and identify breath biomarkers for the early diagnosis of the diseases mentioned above using gas chromatography-mass spectrometry (GC-MS) and secondary electrospray ionisation high-resolution mass spectrometry (SESI-HR-MS). Prescreening will select 120 healthy controls and 175 patients for the baseline phase of the clinical trial, for which breath samples will be collected in 1 L Supel-Inert Multi-Layer Foil gas sampling bags. New biomarkers and VOC profiles will be extracted from these data, and further statistical analysis will allow for artificial intelligence (AI) models to be produced and tested. For phase 2 (validation phase), 120 healthy controls and 100 patients will be selected. Breath samples will again be collected in 1 L gas sampling bags for analyses with GC-MS and SESI-HR-MS. The VOCORDER device will also be used, and its functioning with the newly developed AI models will be evaluated. ETHICS AND DISSEMINATION: This clinical study has been approved by the scientific council at the MITERA hospital in Athens, Greece (#513/2024). The outcomes will be disseminated through peer-reviewed journal publications and presentations at scientific conferences. TRIAL REGISTRATION NUMBER: NCT06711939.