NCT05173077

Brief Summary

The aim of this project is to promote the breath volatile marker concept for colorectal cancer (CRC) screening by advancing developing the application of a novel hybrid analyzer for the purpose. The hybrid analyzer concept is expected to benefit of combining metal-oxide (MOX) and infrared spectrum (IR) sensor acquired data. The current study will be the first globally to address this concept in CRC detection. In addition, traditional methods, in particular, gas chromatography coupled to mass spectrometry (GC-MS) will be used to address the biological relevance of the VOCs emission from cancer tissue and will assist in further advances of the hybrid-sensing approach.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
3,000

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Feb 2022

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 24, 2021

Completed
2 months until next milestone

First Posted

Study publicly available on registry

December 29, 2021

Completed
1 month until next milestone

Study Start

First participant enrolled

February 1, 2022

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 30, 2023

Completed
Last Updated

February 15, 2022

Status Verified

February 1, 2022

Enrollment Period

1.8 years

First QC Date

October 24, 2021

Last Update Submit

February 14, 2022

Conditions

Keywords

Volatile organic compoundsColorectal cancerBreath testing

Outcome Measures

Primary Outcomes (2)

  • Characteristic VOC pattern identification for colorectal 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 colorectal cancer. Volatiles will be separated using an Rt-Q-BOND column working in a constant flow of helium. The column temperature program will be optimized toward detection of observed volatiles. The SCAN, will be used for the untargeted analysis and identification of compounds of breath samples as well as for the quantification of more abundant species. Peak integration will be based on extracted ion chromatograms. The identification of compounds will be performed in two steps. The peak spectrum will be checked against the NIST mass spectral library. The NIST identification will be confirmed by comparing the respective retention times with retention times obtained on the basis of standard mixtures prepared from pure compounds. Whenever possible the VOC emission will be quantified using calibration mixtures prepared from pure liquid or gaseous substances.

    2 years following initiation of patient recruitment

Secondary Outcomes (2)

  • Identification of the best-performing sensors

    3 years following initiation of patient recruitment

  • Gut microbiota analysis in relation to breath VOCs

    3 years following initiation of patient recruitment

Other Outcomes (1)

  • Confounding factor analysis

    3 years following initiation of patient recruitment

Study Arms (5)

Colorectal cancer patients

Patients with histologically confirmed colorectal cancer (adenocarcinoma)

Device: Breath sampling for VOC detectionOther: Blood sample collectionDiagnostic Test: Microbiota testing

Control group patients without colorectal cancer

Patients without colorectal malignant disease according to data obtained in colonoscopy

Device: Breath sampling for VOC detectionOther: Blood sample collectionDiagnostic Test: Microbiota testingDiagnostic Test: Colonoscopy

Average risk population

Average risk population of both genders aged 40-64 at the time of inclusion lacking alarm symptoms for gastrointestinal cancer

Other: Secondary validation study in general CRC screening settingsOther: Blood sample collectionDiagnostic Test: Microbiota testingDiagnostic Test: Colonoscopy

Colorectal cancer patients undergoing surgery

Patients with histologically confirmed colorectal cancer (adenocarcinoma) planned for surgical management

Procedure: Identification of specific VOCs in CRC tissue surgery materialOther: Blood sample collectionDiagnostic Test: Microbiota testing

Patients with polyps undergoing polypectomy

Patients with colon polyps that will perform polypectomy

Device: Breath sampling for VOC detectionOther: Blood sample collectionDiagnostic Test: Microbiota testingDiagnostic Test: Colonoscopy

Interventions

Paired tissue samples will be taken during surgery for CRC. Tissue material from the same patient will be obtained from the cancerous tissue as well as from normal resected material without malignant infiltration. Minimum of 100 mg of each tissue per sample will be obtained. To compare the emission of VOCs in the CRC tissue surgery material to the emissions from normal tissue by GC-MS in a reasonable number of cancer cases.

Colorectal cancer patients undergoing surgery

Altogether at least 1000 individuals relatively healthy 40-64 years old population-based collected individuals will get recruited. Breath samples will be collected by asking the study subjects to breath into hybrid breath analyser. To exclude significant colorectal lesions, laboratory-based FIT testing will be offered to the population cohort group for faecal occult blood in faeces. Serum and plasma samples will also be obtained to have them available if additional testing will be required. Individuals with a FIT test value over the cut-off value (\>10 microg/g faeces) will be invited to colonoscopy. The data analysis procedures and classification models will be tested in this general population and cross-checked against FIT and colonoscopy results.

Average risk population

Breath sampling will be performed by using a hybrid sensor device and or GC-MS analysis (by collecting breath samples in adsorbent tubes). Strict requirements for subjects will be imposed prior to the breath sampling to standardise the breath sampling and to limit the influence of confounding factors.

Colorectal cancer patientsControl group patients without colorectal cancerPatients with polyps undergoing polypectomy

Serum, plasma sampling for group description and stratification.

Average risk populationColorectal cancer patientsColorectal cancer patients undergoing surgeryControl group patients without colorectal cancerPatients with polyps undergoing polypectomy
Microbiota testingDIAGNOSTIC_TEST

Faecal samples for microbiota testing.

Average risk populationColorectal cancer patientsColorectal cancer patients undergoing surgeryControl group patients without colorectal cancerPatients with polyps undergoing polypectomy
ColonoscopyDIAGNOSTIC_TEST

Colonoscopy will be used only according to the clinical indications.

Average risk populationControl group patients without colorectal cancerPatients with polyps undergoing polypectomy

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Cancer patient group: patients with known or suspected colorectal adenocarcinoma being admitted to the major specialized cancer centre in Latvia for diagnostic purpose, medical or surgical management will get recruited. Control group patients will be recruited in the major specialized endoscopy centre (Digestive Diseases Centre "GASTRO") in Latvia. Average m risk population: average risk population of both genders aged 40-64 at the time of inclusion lacking alarsymptoms for gastrointestinal cancer will get recruited. Those will be invited actively from the GP registries or registry of the National Health Services (the regulatory approval for this approach is already available). An equal proportion between the genders will be targeted.

You may qualify if:

  • Adult individuals (\>18 years of age)
  • Having signed the consent form
  • Willingness to collaborate
  • Able to provide a breath sample
  • For the cancer group: colorectal adenocarcinoma has to be documented histologically (histological diagnosis following gastric surgery is also accepted) or patients being confirmed adenocarcinoma during the course of the study.
  • For the non-cancer group: control group - any patient who have medical indications for a colonoscopy

You may not qualify if:

  • The patient has not signed the consent form
  • Patients who have had a complete bowel cleansing
  • Other active malignancies
  • Neoadjuvant chemotherapy, radiation therapy is currently underway
  • Acute conditions (emergency surgery for the patient)
  • Small bowel resection in the past
  • Terminal renal failure (Chronic renal failure stage 4)
  • Type I diabetes
  • Bronchial asthma (active)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Latvia

Riga, Latvia

RECRUITING

Related Publications (14)

  • Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017 Apr;66(4):683-691. doi: 10.1136/gutjnl-2015-310912. Epub 2016 Jan 27.

  • Jurs PC, Bakken GA, McClelland HE. Computational methods for the analysis of chemical sensor array data from volatile analytes. Chem Rev. 2000 Jul 12;100(7):2649-78. doi: 10.1021/cr9800964. No abstract available.

  • van Keulen KE, Jansen ME, Schrauwen RWM, Kolkman JJ, Siersema PD. Volatile organic compounds in breath can serve as a non-invasive diagnostic biomarker for the detection of advanced adenomas and colorectal cancer. Aliment Pharmacol Ther. 2020 Feb;51(3):334-346. doi: 10.1111/apt.15622. Epub 2019 Dec 20.

  • Zhou W, Tao J, Li J, Tao S. Volatile organic compounds analysis as a potential novel screening tool for colorectal cancer: A systematic review and meta-analysis. Medicine (Baltimore). 2020 Jul 2;99(27):e20937. doi: 10.1097/MD.0000000000020937.

  • Sonoda H, Kohnoe S, Yamazato T, Satoh Y, Morizono G, Shikata K, Morita M, Watanabe A, Morita M, Kakeji Y, Inoue F, Maehara Y. Colorectal cancer screening with odour material by canine scent detection. Gut. 2011 Jun;60(6):814-9. doi: 10.1136/gut.2010.218305. Epub 2011 Jan 31.

  • Konvalina G, Haick H. Effect of humidity on nanoparticle-based chemiresistors: a comparison between synthetic and real-world samples. ACS Appl Mater Interfaces. 2012 Jan;4(1):317-25. doi: 10.1021/am2013695. Epub 2011 Dec 15.

  • Hagemann LT, Ehrle S, Mizaikoff B. Optimizing the Analytical Performance of Substrate-Integrated Hollow Waveguides: Experiment and Simulation. Appl Spectrosc. 2019 Dec;73(12):1451-1460. doi: 10.1177/0003702819867342. Epub 2019 Aug 22.

  • Hagemann LT , McCartney MM , Fung AG , Peirano DJ , Davis CE , Mizaikoff B . Portable combination of Fourier transform infrared spectroscopy and differential mobility spectrometry for advanced vapor phase analysis. Analyst. 2018 Nov 19;143(23):5683-5691. doi: 10.1039/c8an01192c.

  • Tutuncu E, Nagele M, Becker S, Fischer M, Koeth J, Wolf C, Kostler S, Ribitsch V, Teuber A, Groger M, Kress S, Wepler M, Wachter U, Vogt J, Radermacher P, Mizaikoff B. Advanced Photonic Sensors Based on Interband Cascade Lasers for Real-Time Mouse Breath Analysis. ACS Sens. 2018 Sep 28;3(9):1743-1749. doi: 10.1021/acssensors.8b00477. Epub 2018 Aug 20.

  • Glockler J, Jaeschke C, Kocaoz Y, Kokoric V, Tutuncu E, Mitrovics J, Mizaikoff B. iHWG-MOX: A Hybrid Breath Analysis System via the Combination of Substrate-Integrated Hollow Waveguide Infrared Spectroscopy with Metal Oxide Gas Sensors. ACS Sens. 2020 Apr 24;5(4):1033-1039. doi: 10.1021/acssensors.9b02554. Epub 2020 Mar 31.

  • Chandrapalan S, Arasaradnam RP. Urine as a biological modality for colorectal cancer detection. Expert Rev Mol Diagn. 2020 May;20(5):489-496. doi: 10.1080/14737159.2020.1738928. Epub 2020 Mar 11.

  • Gasenko E, Leja M, Polaka I, Hegmane A, Murillo R, Bordin D, Link A, Kulju M, Mochalski P, Shani G, Malfertheiner P, Herrero R, Haick H. How do international gastric cancer prevention guidelines influence clinical practice globally? Eur J Cancer Prev. 2020 Sep;29(5):400-407. doi: 10.1097/CEJ.0000000000000580.

  • Lawler M, Alsina D, Adams RA, Anderson AS, Brown G, Fearnhead NS, Fenwick SW, Halloran SP, Hochhauser D, Hull MA, Koelzer VH, McNair AGK, Monahan KJ, Nathke I, Norton C, Novelli MR, Steele RJC, Thomas AL, Wilde LM, Wilson RH, Tomlinson I; Bowel Cancer UK Critical Research Gaps in Colorectal Cancer Initiative. Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer. Gut. 2018 Jan;67(1):179-193. doi: 10.1136/gutjnl-2017-315333.

  • Broza YY, Mochalski P, Ruzsanyi V, Amann A, Haick H. Hybrid volatolomics and disease detection. Angew Chem Int Ed Engl. 2015 Sep 14;54(38):11036-48. doi: 10.1002/anie.201500153. Epub 2015 Jul 31.

Biospecimen

Retention: SAMPLES WITH DNA

Exhaled air samples being stored in specific adsorbent tubes. Plasma/serum samples for group stratification. Faecal samples for occult blood testing and microbiota analysis. Tissue samples for specific VOCs analysis.

MeSH Terms

Conditions

Colorectal NeoplasmsColonic Polyps

Interventions

Colonoscopy

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesIntestinal PolypsPolypsPathological Conditions, AnatomicalPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Endoscopy, GastrointestinalEndoscopy, Digestive SystemDiagnostic Techniques, Digestive SystemDiagnostic Techniques and ProceduresDiagnosisEndoscopyDiagnostic Techniques, SurgicalDigestive System Surgical ProceduresSurgical Procedures, OperativeMinimally Invasive Surgical Procedures

Central Study Contacts

Marcis Leja, MD, PhD

CONTACT

Linda Mezmale, MD

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director, Institute of Clinical and Preventive Medicine

Study Record Dates

First Submitted

October 24, 2021

First Posted

December 29, 2021

Study Start

February 1, 2022

Primary Completion

November 30, 2023

Study Completion

November 30, 2023

Last Updated

February 15, 2022

Record last verified: 2022-02

Data Sharing

IPD Sharing
Will not share

Locations