Clinical trial NCT03699163: The Colorectal Breath Analysis (COBRA) Study
Official title: Non-invasive Testing for the Diagnosis and Assessment of Colorectal Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colorectal Cancer
Colorectal Polyps
Colorectal Adenocarcinoma
Keywords: Volatile organic compounds
Mass spectrometry
Early detection
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Imperial Health Charity
name: Rosetrees Trust
name: National Institute for Health Research, United Kingdom
First posted: 2018-10-09
Enrollment: 1855
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who are attending for a planned colonoscopy or who are scheduled to undergo elective resection of histologically confirmed colorectal adenocarcinoma will be eligible for inclusion in this study

Brief summary: This study aims to determine whether a breath test could be used for early detection of colorectal cancer and colorectal polyps.

Patients who are attending for a planned colonoscopy or who are scheduled to undergo elective resection of histologically confirmed colorectal cancer (adenocarcinoma) will be approached to provide a breath sample.

Multi platform mass spectrometry analysis will be performed to establish volatile biomarkers that can discriminate between colorectal cancer, benign colorectal disease (e.g. polyps) and healthy controls.

Detailed description: Colorectal cancer is the 2nd most common cause of cancer death in the UK where survival rates are among the lowest in Europe. If diagnosed early survival may exceed 90%.

The proposed breath test is a non-invasive investigation that can detect the presence of volatile organic compounds (VOCs) in breath and their relative abundance in disease states including colorectal cancer. This test has potential to be used in a primary care setting to identify patients at high risk of colorectal cancer, supporting earlier referral for definitive investigation. A negative test may provide reassurance to patients and prevent unnecessary tests in this group. The test could also have an application for colorectal cancer screening.

In this study the investigators will determine the diagnostic accuracy of an exhaled breath test for the detection of colorectal adenocarcinoma and colonic polyps. To determine the accuracy of the breath test a multicentre cross-sectional study will be conducted to analyse single breath samples from patients attending hospital for planned colonoscopy or elective resection of histologically confirmed colorectal cancer. The target for the study is 1463 patients.

Breath collection will be conducted using a previously validated method. Samples of breath (500ml) collected using a CE-marked handheld ReCIVA sampling device (Owlstone Medical Ltd., Cambridge, UK) during a period of tidal breathing (approximately 5minutes) will be absorbed onto thermal desorption tubes (Markes International, Llantrisant, UK). All patients will have received bowel preparation and will be fasted for a minimum of 6 hours prior to the breath sample. Breath samples collected within thermal desorption tubes will be transferred to a central laboratory for analysis by gas chromatography mass spectrometry (GC-MS) and proton transfer reaction time of flight mass spectrometry (PTR-ToF-MS). Raw data files will be extracted and analysed in accordance with established protocols. Quality assurance measures will be formally assessed at each stage of sample handling.

Eligibility criteria: Inclusion Criteria:

* ≥18 years and ≤90 years of age
* Undergoing planned colonoscopy or elective resection of histologically confirmed colorectal adenocarcinoma
* Fasted \>6 hours
* Able to provide informed written consent

Exclusion Criteria:

* Any patient \<18 years or \>90 years of age.
* Lacks capacity or is unable to provide informed written consent.

Primary outcomes:
measure: Determine the Diagnostic Accuracy of the Proposed Breath Test for Detection of Colorectal Cancer in All Patients
timeFrame: 30 minutes
measure: Determine the Diagnostic Accuracy of Using VOCs Present in Breath for the Detection of Colorectal Cancer in Symptomatic Patients
timeFrame: 30 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Homerton Hospital
city: London
country: United Kingdom
facility: St Mark's Hospital
city: London
country: United Kingdom
facility: St George's Hospital
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: London
country: United Kingdom
facility: West Middlesex Hospital
city: London
country: United Kingdom
facility: St Mary's Hospital
city: London
country: United Kingdom
facility: Charing Cross Hospital
Study officials:
affiliation: Imperial College London
name: George B Hanna, FRCS PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Woodfield G, Belluomo I, Laponogov I, Veselkov K; COBRA1 WORKING GROUP; Cross AJ, Hanna GB. Diagnostic Performance of a Noninvasive Breath Test for Colorectal Cancer: COBRA1 Study. Gastroenterology. 2022 Nov;163(5):1447-1449.e8. doi: 10.1053/j.gastro.2022.06.084. Epub 2022 Jul 5. No abstract available.