Hybrid-sensor Breath Analysis for Colorectal Cancer Screening

• Conditions: Polyp of Colon; Colorectal Cancer
• Interventions: Device: Breath sampling for VOC detection; Other: Secondary validation study in general CRC screening settings; Procedure: Identification of specific VOCs in CRC tissue surgery material; Other: Blood sample collection; Diagnostic Test: Microbiota testing; Diagnostic Test: Colonoscopy

• Registration Number: NCT05173077
• Lead Sponsor: University of Latvia

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.

Detailed Description

For addressing the aims of the project, four specific research objectives have been set:

1. To identify cancer-related VOCs emitted by the CRC tissue via the comparison of VOCs emitted from cancer tissue with VOCs emitted by non-cancerous tissue (ex vivo surgery material) by GC-MS.

2. To identify the VOCs differentiating human breath from CRC patients and controls (by GC-MS) as well as compare the chemical signature of CRC patients' breath to the chemical signature of cancer tissue.

3. To evaluate the performance of the set of sensors in the hybrid analyzer and the performance of particular sensors for detecting CRC; to develop and validate a mathematical model for CRC detection.

4. To validate the hybrid analyzer in real-life CRC screening settings, i.e. versus the generally accepted CRC screening approach of faecal occult blood detection.

5. To compare faecal microbiome between CRC group and control.

The scientific results to be obtained during the current project are expected to elucidate the origin and metabolism of volatile biomarkers of CRC. This achievement, in turn, will facilitate the implementation of a new screening test based on the newly developed hybrid analyser into medical practice.

Identification of the VOCs patterns by the sensor array for CRC patients when compared to controls. Addressing these objectives will allow an in-depth understanding of the physiological background for exhaled VOCs in CRC patients and facilitate the development of technologies able to identify the disease and its precursors from an exhaled breath sample.

Study Timeline

• Study First Submitted: 2021-10-24
• Study First Submitted QC: 2021-12-10
• Study First Posted: 2021-12-29
• Status Verified: 2022-02
• Study Start: 2022-02-01
• Last Update Submitted: 2022-02-14
• Last Update Posted: 2022-02-15
• Primary Completion: 2023-11-30
• Study Completion: 2023-11-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 3000

Inclusion Criteria

• 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

Exclusion Criteria

• 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)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Colorectal cancer patients	Breath sampling for VOC detection	Patients with histologically confirmed colorectal cancer (adenocarcinoma)
Average risk population	Secondary validation study in general CRC screening settings	Average risk population of both genders aged 40-64 at the time of inclusion lacking alarm symptoms for gastrointestinal cancer
Colorectal cancer patients undergoing surgery	Blood sample collection	Patients with histologically confirmed colorectal cancer (adenocarcinoma) planned for surgical management
Average risk population	Blood sample collection	Average risk population of both genders aged 40-64 at the time of inclusion lacking alarm symptoms for gastrointestinal cancer
Colorectal cancer patients undergoing surgery	Identification of specific VOCs in CRC tissue surgery material	Patients with histologically confirmed colorectal cancer (adenocarcinoma) planned for surgical management
Patients with polyps undergoing polypectomy	Microbiota testing	Patients with colon polyps that will perform polypectomy
Control group patients without colorectal cancer	Breath sampling for VOC detection	Patients without colorectal malignant disease according to data obtained in colonoscopy
Control group patients without colorectal cancer	Colonoscopy	Patients without colorectal malignant disease according to data obtained in colonoscopy
Patients with polyps undergoing polypectomy	Colonoscopy	Patients with colon polyps that will perform polypectomy
Colorectal cancer patients undergoing surgery	Microbiota testing	Patients with histologically confirmed colorectal cancer (adenocarcinoma) planned for surgical management
Colorectal cancer patients	Blood sample collection	Patients with histologically confirmed colorectal cancer (adenocarcinoma)
Colorectal cancer patients	Microbiota testing	Patients with histologically confirmed colorectal cancer (adenocarcinoma)
Control group patients without colorectal cancer	Microbiota testing	Patients without colorectal malignant disease according to data obtained in colonoscopy
Control group patients without colorectal cancer	Blood sample collection	Patients without colorectal malignant disease according to data obtained in colonoscopy
Average risk population	Microbiota testing	Average risk population of both genders aged 40-64 at the time of inclusion lacking alarm symptoms for gastrointestinal cancer
Average risk population	Colonoscopy	Average risk population of both genders aged 40-64 at the time of inclusion lacking alarm symptoms for gastrointestinal cancer
Patients with polyps undergoing polypectomy	Breath sampling for VOC detection	Patients with colon polyps that will perform polypectomy
Patients with polyps undergoing polypectomy	Blood sample collection	Patients with colon polyps that will perform polypectomy

Primary Outcome Measures

Name	Time	Method
Characteristic VOC pattern identification for colorectal cancer detection	2 years following initiation of patient recruitment	The characteristic VOC pattern based on sensor analysis and its performance indicators will be detected.
Specific chemistry identification in the exhaled breath	2 years following initiation of patient recruitment	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.

Secondary Outcome Measures

Name	Time	Method
Gut microbiota analysis in relation to breath VOCs	3 years following initiation of patient recruitment	Analysis of the role of faecal microbiota in the origin of VOCs in the exhaled breath.
Identification of the best-performing sensors	3 years following initiation of patient recruitment	Decision on the optimal set of breath sensors that potentially will be included in a sensor analyser for CRC detection. Comparative analysis between the performance of different sensor performance in target disease identification.

Trial Locations

Locations (1)

University of Latvia; 🇱🇻 Riga, Latvia