Volatiles in Breath and Headspace Analysis - Diagnostic Markers

Colorectal Cancer Clinical Trial

— Volatolome  

Official title:

Volatile Organic Compounds in Breath and Headspace Analysis - Diagnostic and Monitoring Markers for Diseases

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03228095
• Other study ID #: 2017/20329
• Status: Enrolling by invitation
• Start date: July 24, 2017
• Est. completion date: December 31, 2025

Study information

• Verified date: August 2018
• Source: University of Latvia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Detection of Volatile Organic Compounds (VOC) directly from tissue by headspace analysis (skin, surgery material, other tissue) and exhaled breath is feasible using affordable user-friendly novel nano-chemo sensors that can accurately be used for screening and monitoring purpose

Description:

Study propose to explore a novel approach for the diagnosis and monitoring of diseases. The approach is based on the detection of volatile organic compounds (VOCs) that are emitted from the cells and detected directly from tissue, such as skin, surgery material, blood as well as from exhaled breath.

In the literature there are several reports on VOCs which can be detected by Gas Chromatography - Mass Spectrometry (GC-MS) means directly from: (i) the headspace of TB cells (i.e., the mixture of volatile biomarkers trapped above the TB cells in a sealed vessel); (ii) the exhaled breath or (iii) from urine. Excellent results in detection of the tuberculosis disease by using nanosensor array were shown by Nakhleh et al achieved 90% sensitivity, 93% specificity and 92% accuracy in discrimination between healthy and diseased patients using electronic nose devices with a single sensor. None of the reported studies identified the tentative recognition of the tuberculosis-related VOCs and quantified the concentration differences between samples from ill and healthy controls. Further investigation of the exhaled breath tuberculosis-related VOC by GC-MS means will improve the knowledge and simultaneously will help to improve the nanosensor array design.

Several studies have shown that disease-rated VOC patterns can be transmitted through the skin, and, therefore, skin can be used as a source for disease detection and identification. The principle of this detection approach is that disease-related changes are reflected in measurable changes in the skin through exchange via the blood. In addition, several studies have suggested that the VOC levels are elevated even in early stages of the disease, because they reflect a change in the human's body chemistry (as a result of the development of disease condition), rather than the amount of infected cells. Complementary studies have shown that VOCs can be emitted to the skin within minutes after they have emerged in the infected part of the human's body. What is particularly significant about this approach is that each type of (infectious) disease has its own unique pattern of VOCs, and, therefore, the presence of one (infectious) disease would not screen other disease types. Nevertheless, to the best of our knowledge, the detection of tuberculosis VOCs through skin has not been examined yet. Additionally, all studies targeting skin VOCs have been carried out by means of spectrometry and spectroscopy techniques. In few cases, electronic nose devices were used. These techniques are powerful tools for detecting VOCs. However, to date, the use of these techniques has been impeded by the need for moderately to highly expensive equipment's, the high levels of expertise required to operate such instruments, the speed required for sampling and analysis, and the need for preconcentration techniques. For VOC skin testing and breath testing of tuberculosis to become widely used in clinical practice, several advances in the knowledge of tuberculosis specific VOCs and sensor development need to occur. Nanoparticles containing flexible sensors, based on organic films, are more likely to become a clinical diagnostic tool, because they are significantly smaller, easier-to-use, and significantly less expensive.

In recent years comprehensive studies have shown excellent data for using VOCs from exhaled breath as tool for diagnosing gastric cancer. In one of the biggest studies carried out by Chinese and Latvian centers, malignancy could be identified with 89% sensitivity and 90% specificity after cross-validation, irrespective of important confounding factors in gastric patients such as tobacco or alcohol consumption and H. pylori infection. A breath test for GC staging could also be demonstrated by distinguishing stage I&II cancers from stage III&IV cancers with 89% sensitivity and 94% specificity. These studies used both - mass spectometry and nano-sensors technologies. Most recent study published in ASC Nano journal in January 2017 reported on more extended use of nanoarry sensors in breath analysis, blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined (chronic kidney failure, idiopathic Parkinson's disease, atypical Parkinsonism , multiple sclerosis, Crohn's disease, ulcerative colitis, irritable bowel syndrome, pulmonary arterial hypertension, pre-eclampsia in pregnant women, head and neck cancer, lung cancer, colorectal cancer, bladder cancer, kidney cancer, prostate cancer, gastric cancer, and ovarian cancer. Analysis of the artificially intelligent nanoarray also showed that each disease has its own unique breathprint, and that the presence of one disease would not screen out others.

Therefore, this study is aimed to test VOCs detecting technologies as diagnostic and monitoring tools for digestive tract and infectious diseases.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 3000
• Est. completion date: December 31, 2025
• Est. primary completion date: December 20, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Informed Consent signed

• Individual with targeted disease/lesion (tuberculosis, gastric cancer, gastric dysplasia, high/ normal/ low risk gastric lesions, colorectal cancer, high-risk colorectal lesions, low-risk colorectal adenoma, pancreatic cancer, chronic pancreatitis, liver cancer, chronic liver disease, other infectious diseases, oncological diseases of other location)

Exclusion Criteria:

• Informed Consent not signed

• Other active cancer at the time of inclusion for particular study group

Related Conditions & MeSH terms

• Adenoma
• Atrophic Gastritis
• Colorectal Adenoma
• Colorectal Cancer
• Colorectal Neoplasms
• Colorectal Polyp
• Communicable Diseases
• Flu, Human
• Gastric Cancer
• Gastric Dysplasia
• Gastritis
• Gastritis, Atrophic
• Infection
• Inflammatory Bowel Diseases
• Influenza, Human
• Intestinal Metaplasia
• Liver Cancer
• Liver Cirrhosis
• Liver Neoplasms
• Metaplasia
• Other Infectious Diseases
• Pancreatic Cancer
• Pancreatic Neoplasms
• Pancreatitis
• Pancreatitis, Chronic
• Peptic Ulcer
• Stomach Neoplasms
• Tuberculosis

Intervention

Diagnostic Test:
• VOC detection in breath and in skin headspace
VOC will be detected in breath with off-line and on-line testing and in skin headspace with off-line testing
• Breath sampling
Breath sampling for VOCs detections will be carried out using nano-sensor based devices (electronic nose)

Procedure:
• Upper endoscopy with biopsies
Upper endoscopy with proper biopsy work-up will be used for identification and stratification of gastric lesions as well as acquisition of biopsies for microbiota testing
• Colonoscopy with biopsies
Colonoscopy with proper biopsy or polypectomy material work-up will be used for identification and stratification of colorectal lesions as well as acquisition of biopsies for microbiota testing
• Whole blood/ Plasma / serum sampling
Whole blood/Plasma/serum sampling will be used to obtain information for group stratification

Diagnostic Test:
• Faecal sampling
Facal samples will be obtained for faecal occult blood testing as well as microbiota analysis

Procedure:
• Histological examination of surgical specimen
Routine histological exam for patients undergoing curative or palliative surgery. Indication for surgery are set based on underlying condition. Study does not interfere with decision making for surgical treatment

Diagnostic Test:
• Headspace analysis for biological material
VOC analysis from headspace of surgical specimen, biopsy materials, blood/plasma, microbiota etc.

Locations

Country	Name	City	State
Latvia	University of Latvia	Riga

Sponsors (4)

Lead Sponsor	Collaborator
University of Latvia	JLM Innovation GmbH, Riga East University Hospital, Technion, Israel Institute of Technology

Country where clinical trial is conducted

Latvia, 

References & Publications (3)

Amal H, Leja M, Broza YY, Tisch U, Funka K, Liepniece-Karele I, Skapars R, Xu ZQ, Liu H, Haick H. Geographical variation in the exhaled volatile organic compounds. J Breath Res. 2013 Dec;7(4):047102. doi: 10.1088/1752-7155/7/4/047102. Epub 2013 Nov 1. — View Citation

Nakhleh MK, Amal H, Jeries R, Broza YY, Aboud M, Gharra A, Ivgi H, Khatib S, Badarneh S, Har-Shai L, Glass-Marmor L, Lejbkowicz I, Miller A, Badarny S, Winer R, Finberg J, Cohen-Kaminsky S, Perros F, Montani D, Girerd B, Garcia G, Simonneau G, Nakhoul F, Baram S, Salim R, Hakim M, Gruber M, Ronen O, Marshak T, Doweck I, Nativ O, Bahouth Z, Shi DY, Zhang W, Hua QL, Pan YY, Tao L, Liu H, Karban A, Koifman E, Rainis T, Skapars R, Sivins A, Ancans G, Liepniece-Karele I, Kikuste I, Lasina I, Tolmanis I, Johnson D, Millstone SZ, Fulton J, Wells JW, Wilf LH, Humbert M, Leja M, Peled N, Haick H. Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules. ACS Nano. 2017 Jan 24;11(1):112-125. doi: 10.1021/acsnano.6b04930. Epub 2016 Dec 21. — View Citation

Xu ZQ, Broza YY, Ionsecu R, Tisch U, Ding L, Liu H, Song Q, Pan YY, Xiong FX, Gu KS, Sun GP, Chen ZD, Leja M, Haick H. A nanomaterial-based breath test for distinguishing gastric cancer from benign gastric conditions. Br J Cancer. 2013 Mar 5;108(4):941-50. doi: 10.1038/bjc.2013.44. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Specific VOC detected	Tuberculosis specific VOC detected in breath and in skin headspace	2 years
Primary	Performance of nanoarray sensor testing to detect target lesions and diseases	Sensitivity, specificity, overall accuracy of nanoarray sensor testing for VOCs to detect the target lesions in the blinded analysis	At the time of breath sampling
Secondary	Specific VOC patterns for target disease or lesion and risk groups	List of VOCs assayed by GC-MS with statistical difference between the study groups	At the time of breath sampling
Secondary	VOC pattern changes following treatment	VOC pattern changes after specific required treatment (medical eradication of bacteria/viruses, surgery/endoscopic removal for cancers or high risk lesion)	At baseline, 3 and/or 6 months after treatment (other time frame according to study group)
Secondary	VOC pattern changes in relapse of disease for early recognition and treatment	VOC pattern changes at the time of surveillance in case of relapse (malignant diseases).	At baseline, 3 and/or 6 months after treatment (other time frame according to study group)
Secondary	Groups of gastrointestinal microbiota correlating to VOCs	List of gastrointestinal microbiota groups (phylum/genus level) with positive correlation to particular VOCs	At the time of sampling