Breath Analysis as an Additional Test for Colorectal Cancer Screening to Reduce the Number of Unnecessary Colonoscopies

Study Overview
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Brief Summary
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In the past decade, the demand for colonoscopy procedures has increased significantly since the introduction of population-based colorectal cancer (CRC) screening in many western countries. Post-polypectomy surveillance will increase the number of colonoscopy procedures conducted each year even further. The invasive nature of colonoscopy and the associated health-care costs warrant the development of a new non-invasive test to reduce the number of unnecessary colonoscopies. These days, many countries use a non-invasive fecal test for CRC screening which is easy to perform at home, but test characteristics such as sensitivity and specificity are suboptimal. Multiple studies have already shown that volatile organic compound (VOC) analysis has a high diagnostic accuracy for CRC and Advanced Adenomas. An additional VOC analysis, for example through breath testing, in patients with a positive fecal immunochemical test (FIT) may reduce the number of unnecessary colonoscopies. The aim of this study is to validate the diagnostic accuracy of the AeonoseTM to distinguish patients with CRC from healthy controls, and to assess reproducibility of test results.

Detailed Description
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Rationale: An electronic nose (eNose) is an artificial olfactory system that analyses volate organic compounds (VOCs) in exhaled breath. Exhaled human breath is mainly composed of inorganic compounds, inert gases and VOCs. VOCs are exhaled in very low concentrations and reflect pathological processes such as inflammation, oxidation, infection and neoplasms. The perspective is that metabolic and biochemical processes in several pathological situations cause different endogenous VOCs to arise, were they can serve as non-invasive biomarkers for certain diseases. Primary objective: To evaluate if the use of an additional breath test (AeonoseTM) for patients with a positive FIT-test can reduce the number of unnecessary colonoscopies. Secondary objectives: External validation of results for CRC and (advanced) adenoma detection established in a previous studies (second study not yet published). (15) To evaluate if VOC profiles in breath are similar at two different time points. Acceptance rate of using the AeonoseTM device for VOC analysis in participating patients. Study population: Patients between the ages of 55 and 75 years old with a positive FIT-test referred for a colonoscopy procedure. Estimated sample size: 750 participants Intervention: Participants will be asked to breath through the AeonoseTM for 5 minutes during pre-colonoscopy intake and just prior to the procedure to assess reproducibility (with >2 weeks in between). There are no risks, nor benefits for the participants.

Official Title
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Breath analysiS as an Additional Test for ColoREctal cancEr screeNing to rEduce the Number of unnecessaRy Colonoscopies

Conditions
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Colorectal Cancer, Polyp of Colon, Colorectal Neoplasms

Intervention / Treatment
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* Device: AeonoseTM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients between the ages of 55 and 75 years referred for a colonoscopy procedure after a positive FIT test, according to the population based CRC screening program in the Netherlands Exclusion Criteria: Prior surgical resection of any portion of the colon History of any type of malignancy, not including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) Current active colitis or history of polyposis syndrome

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: This is a multicenter prospective cohort study in participants eligible for colonoscopy with suspicion for (pre)malignant lesions of the colon
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Patients referred for colonoscopy<br> | Device: AeonoseTM<br>* All participants will be asked to breathe into an electronic nose (eNose, the AeonoseTM, The eNose Company, Zutphen, the Netherlands) for 5 minutes during the pre-colonoscopy intake and just prior to the procedure to assess reproducibility (with >2 weeks in between).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic accuracy in distinguishing colorectal carcinoma from healthy controls | The diagnostic accuracy, in terms of sensitivity and specificity, of the AeonoseTM in distinguishing between patients with and without CRC. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic accuracy in distinguishing advanced adenoma from healthy controls | Sensitivity and specificity | 12 months | 
| Reproducibility | The variation in VOC analysis results between two separate time points. The binary results from the eNose analysis will be presented in a scatterplot and a receiver operating characteristics curve (ROC-curve). Cohen's kappa statistic will be applied to determine interobserver agreement between the eNose results of 2 different timepoints (>2 weeks apart) | 12 months | 
| Acceptance rate | The acceptance rate of using the AeonoseTM in participating patients. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aeonose, Volatile organic compounds, VOC, Colorectal cancer, Advanced adenoma, Breath test, Electronic nose, eNose