Screening of Gastric Cancer Via Breath Volatile Organic Compounds by Hybrid Sensing Approach (VOGAS)

The study is aimed to determine the potential of volatile marker testing for gastric cancer screening.

The study will be addressing the role of confounding factors, including lifestyle factors, diet, smoking as well as addressing the potential role of microbiota in the composition of exhaled volatile markers.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Gastric Dysplasia; Atrophic Gastritis; H.Pylori Infection
• Intervention / Treatment: Device: Breath sampling for VOC detection; Procedure: Surgery material collection for VOC headspace analysis; Diagnostic test: Upper endoscopy; Diagnostic test: Microbiota testing

Detailed Description

Patients with established disease (gastric cancer, precancerous lesions) as well as patients investigated for the lesions and having been documented lack of the lesions will be enrolled to the study at clinical sites in Europe (Latvia, Ukraine) and Latin America (Colombia, Chile, Brazil). In addition, group of persons from general population at average risk for developing the target disease and individuals being referred for upper endoscopy according to clinical indications will be also enrolled.

Testing of volatile markers will be conducted by one of two methods: 1) gas chromatography coupled to mass spectroscopy (GS-MS) and 2) sensor technology. Various sensors will be used and evaluated for the purpose.

The potential sources of volatile organic compounds (VOCs) in the breath will be addressed by studying VOC emission by using headspace analysis from cancer tissue, gastric contents, cancer cell cultures and H.pylori.

The potential role of gastric and faecal microbiota in the origin of VOCs in the breath will be addressed. Metabolome in the circulation will also get correlated to VOCs in the breath and with microbiome.

• Study Type: Observational
• Enrollment (Anticipated): 5000

Contacts and Locations

• Study Contact: Name: Daiga Santare, MD, PhD; Phone Number: +37129221107; Email: daiga.santare@lu.lv

Study Locations

• Brazil
  • São Paulo, Brazil
    • Recruiting
    • A.C.Camargo Cancer Center
    • Contact: Emmanuel Dias Neto, MD, PhD; Email: emmanuel@accamargo.org.br
• Chile
  • Santiago, Chile
    • Not yet recruiting
    • Pontificia Universidad Catolica de Chile
    • Contact: Robinson Gonzalez, MD, PhD; Email: robgonza@med.puc.cl
    • Contact: Alejandro Corvalan, MD, PhD; Email: corvalan01@gmail.com
• Colombia
  • Bogotá, Colombia
    • Not yet recruiting
    • Centro Javeriano de Oncología, San Ignacio University Hospital
    • Contact: Raul Murillo, MD, PhD; Email: raulhmurillo@yahoo.com
• Latvia
  • Riga, Latvia, LV1050
    • Recruiting
    • Institute of Clinical and Preventive Medicine, University of Latvia
    • Contact: Daiga Santare, MD, PhD; Phone Number: +37129221107; Email: daiga.santare@lu.lv
• Ukraine
  • Kiev, Ukraine
    • Recruiting
    • National Cancer Institute of Ukraine
    • Contact: Andrii Lukashenko, MD, PhD; Email: mail.onco@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Cancer patient population will be recruited in the major specialized cancer centres in Europe (Latvia, Ukraine) and Latin America (Colombia, Chile, Brazil) Control group patients will be recruited in the major specialized endoscopy centres in Europe (Latvia, Ukraine) and Latin America (Colombia, Chile, Brazil), most frequently - the same institutions as for cancer patient recruitment General population group (40-64 years) will be predominantly recruited in Latvia from the general population Symptomatic patient validation cohort (Group 5) will be predominantly recruited in Chile from the endoscopy referrals

Description

Inclusion Criteria:

• Patients with verified gastric cancer (Group 1 & 2)
• Patients undergoing or having undergone upper endoscopy according to clinical indications (Group 3 & 5)
• Average-risk population group aged 40-64 at inclusion without alarm symptoms (Group 4)
• Motivation to participate in the study
• Physical status allowing volatile marker sampling and other procedures within the protocol
• Signed consent

Exclusion Criteria:

• Known other active cancer
• Ventilation problems, airway obstruction
• Unwillingness or inability to co-operate

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Gastric cancer patients undergoing surgery; Patients with histologically confirmed gastric cancer (adenocarcinoma) planned for surgical management	Device: Breath sampling for VOC detection; Breath sampling will be performed by using a special sensor device and or GC-MS analysis (by collecting breath samples in adsorbent tubes). Pepsinogen testing will be used in a subgroup to identify serological increased risk for atrophy; Other Names: Serum, plasma sampling for group description and stratification; Procedure: Surgery material collection for VOC headspace analysis; Only for gastric cancer patients undergoing surgery (Group 1); Diagnostic test: Upper endoscopy; Routine endoscopic evaluation with a standard biopsy work-up according to updated Sydney system. Additional gastric contents for GC-MS and microbiota analysis in a subgroup. Endoscopy will be used only according to the clinical indications (in Group 4 - according to the results of pepsinogen tests); Other Names: Histological and microbial evaluation of biopsy samples and gastric content; Diagnostic test: Microbiota testing; Faecal and gastric contents and biopsy samples for microbiota testing
Gastric cancer patients; Patients with histologically confirmed gastric cancer (adenocarcinoma)	Device: Breath sampling for VOC detection; Breath sampling will be performed by using a special sensor device and or GC-MS analysis (by collecting breath samples in adsorbent tubes). Pepsinogen testing will be used in a subgroup to identify serological increased risk for atrophy; Other Names: Serum, plasma sampling for group description and stratification; Diagnostic test: Upper endoscopy; Routine endoscopic evaluation with a standard biopsy work-up according to updated Sydney system. Additional gastric contents for GC-MS and microbiota analysis in a subgroup. Endoscopy will be used only according to the clinical indications (in Group 4 - according to the results of pepsinogen tests); Other Names: Histological and microbial evaluation of biopsy samples and gastric content; Diagnostic test: Microbiota testing; Faecal and gastric contents and biopsy samples for microbiota testing
Control group patients without gastric cancer; Patients without gastric malignant disease according to data obtained in upper endoscopy	Device: Breath sampling for VOC detection; Breath sampling will be performed by using a special sensor device and or GC-MS analysis (by collecting breath samples in adsorbent tubes). Pepsinogen testing will be used in a subgroup to identify serological increased risk for atrophy; Other Names: Serum, plasma sampling for group description and stratification; Diagnostic test: Upper endoscopy; Routine endoscopic evaluation with a standard biopsy work-up according to updated Sydney system. Additional gastric contents for GC-MS and microbiota analysis in a subgroup. Endoscopy will be used only according to the clinical indications (in Group 4 - according to the results of pepsinogen tests); Other Names: Histological and microbial evaluation of biopsy samples and gastric content; Diagnostic test: Microbiota testing; Faecal and gastric contents and biopsy samples for microbiota testing
Average risk population; Average risk population of both genders aged 40-64 at the time of inclusion lacking alarm symptoms for gastrointestinal cancer	Device: Breath sampling for VOC detection; Breath sampling will be performed by using a special sensor device and or GC-MS analysis (by collecting breath samples in adsorbent tubes). Pepsinogen testing will be used in a subgroup to identify serological increased risk for atrophy; Other Names: Serum, plasma sampling for group description and stratification; Diagnostic test: Upper endoscopy; Routine endoscopic evaluation with a standard biopsy work-up according to updated Sydney system. Additional gastric contents for GC-MS and microbiota analysis in a subgroup. Endoscopy will be used only according to the clinical indications (in Group 4 - according to the results of pepsinogen tests); Other Names: Histological and microbial evaluation of biopsy samples and gastric content; Diagnostic test: Microbiota testing; Faecal and gastric contents and biopsy samples for microbiota testing
Patients with dyspeptic symptoms; Patients with dyspeptic symptoms or other complains being referred for upper endoscopy (Chile)	Device: Breath sampling for VOC detection; Breath sampling will be performed by using a special sensor device and or GC-MS analysis (by collecting breath samples in adsorbent tubes). Pepsinogen testing will be used in a subgroup to identify serological increased risk for atrophy; Other Names: Serum, plasma sampling for group description and stratification; Diagnostic test: Upper endoscopy; Routine endoscopic evaluation with a standard biopsy work-up according to updated Sydney system. Additional gastric contents for GC-MS and microbiota analysis in a subgroup. Endoscopy will be used only according to the clinical indications (in Group 4 - according to the results of pepsinogen tests); Other Names: Histological and microbial evaluation of biopsy samples and gastric content; Diagnostic test: Microbiota testing; Faecal and gastric contents and biopsy samples for microbiota testing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characteristic VOC pattern identification for gastric cancer detection	The characteristic VOC pattern based on sensor analysis and its performance indicators will be detected	2 years following initiation of patient recruitment
Specific chemistry identification in the exhaled breath	Identification of specific chemistries (GC-MS analysis) originating from gastric cancer	2 years following initiation of patient recruitment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characteristic VOC pattern identification for gastric precancerous lesion detection	The characteristic VOC pattern based on sensor analysis and its performance indicators will be detected	2.5 years following initiation of patient recruitment
Identification of the best-performing sensors	Comparative analysis between the performance of different sensor performance in target disease identification	3 years following initiation of patient recruitment
Gut microbiota analysis in relation to breath VOCs	Analysis of the role of gastric and faecal microbiota in the origin of VOCs in the exhaled breath	3 years following initiation of patient recruitment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confounding factor analysis	The role of confounding factors will be addressed to address their role in VOC emission	3 years following initiation of patient recruitment

Collaborators and Investigators

• Sponsor: University of Latvia
• Collaborators: Uppsala University; Pontificia Universidad Catolica de Chile; Technion, Israel Institute of Technology; Hospital Universitario San Ignacio; University of Ulm; AC Camargo Cancer Center; VTT Technical Research Centre of Finland; Universitaet Innsbruck; JLM Innovation GmbH; Universidad de Pamplona; National Cancer Institute of Ukraine
• Investigators: Principal Investigator: Hossam Haick, PhD, TECHNION, Israel Institute for Technology

Publications and helpful links

General Publications

• Mochalski P, Leja M, Gasenko E, Skapars R, Santare D, Sivins A, Aronsson DE, Ager C, Jaeschke C, Shani G, Mitrovics J, Mayhew CA, Haick H. Ex vivo emission of volatile organic compounds from gastric cancer and non-cancerous tissue. J Breath Res. 2018 Jul 30;12(4):046005. doi: 10.1088/1752-7163/aacbfb.
• Krilaviciute A, Stock C, Leja M, Brenner H. Potential of non-invasive breath tests for preselecting individuals for invasive gastric cancer screening endoscopy. J Breath Res. 2018 Apr 4;12(3):036009. doi: 10.1088/1752-7163/aab5be.
• Amal H, Leja M, Funka K, Skapars R, Sivins A, Ancans G, Liepniece-Karele I, Kikuste I, Lasina I, Haick H. Detection of precancerous gastric lesions and gastric cancer through exhaled breath. Gut. 2016 Mar;65(3):400-7. doi: 10.1136/gutjnl-2014-308536. Epub 2015 Apr 13.
• Krilaviciute A, Heiss JA, Leja M, Kupcinskas J, Haick H, Brenner H. Detection of cancer through exhaled breath: a systematic review. Oncotarget. 2015 Nov 17;6(36):38643-57. doi: 10.18632/oncotarget.5938.
• Leja M, You W, Camargo MC, Saito H. Implementation of gastric cancer screening - the global experience. Best Pract Res Clin Gastroenterol. 2014 Dec;28(6):1093-106. doi: 10.1016/j.bpg.2014.09.005. Epub 2014 Sep 28.
• Leja M, Amal H, Lasina I, Skapars R, Sivins A, Ancans G, Tolmanis I, Vanags A, Kupcinskas J, Ramonaite R, Khatib S, Bdarneh S, Natour R, Ashkar A, Haick H. Analysis of the effects of microbiome-related confounding factors on the reproducibility of the volatolomic test. J Breath Res. 2016 Jun 24;10(3):037101. doi: 10.1088/1752-7155/10/3/037101.

Helpful Links

• Horizon 2020 project VOGAS web-page

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: July 12, 2019
• First Submitted That Met QC Criteria: July 12, 2019
• First Posted (Actual): July 16, 2019

Study Record Updates

• Last Update Posted (Actual): July 26, 2021
• Last Update Submitted That Met QC Criteria: July 19, 2021
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Gastric cancer; Screening; GC-MS; Volatile organic compounds; Breath testing; Atrophic gastritis; Precancerous lesions; Nanosensor technology
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Pathological Conditions, Anatomical; Stomach Neoplasms; Gastritis; Atrophy; Gastritis, Atrophic
• Other Study ID Numbers: 824986; lzp-2018/2-0228 (Other Grant/Funding Number: Latvia Research Council); KC-L-2017/5 (Other Grant/Funding Number: Investment and Development Agency of Latvia)

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