Detection of Colorectal Cancer in Patients With a Positive Fecal Immunochemical Test Using an Electronic Nose Device (AeoNoseTM)

The present study aims to investigate the diagnostic accuracy of exhaled breath analysis with the Aeonose (the eNose Company, Zutphen, the Netherlands) to distinguish the breath of patients suspected for CRC (based on a positive fecal immunochemical test), who are truly diagnosed with CRC, from patients suspected for CRC in whom this diagnosis is rejected after colonoscopy.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Polyps of Colon
• Intervention / Treatment: Device: Aeonose

Detailed Description

Study rationale:

Colonoscopy plays a key role in all colorectal cancer (CRC) screening modalities. An important limitation of colonoscopy remains that the diagnostic accuracy and therapeutic safety of colonoscopy both depend on several physician and patient-related factors. Significant amounts of polyps are missed during colonoscopy and severe untoward effects still occur in 0.1%-0.3% of all colonoscopy procedures, even among expert examiners. Moreover, the burdensome nature of the procedure and the necessity of full bowel preparation negatively influences participation rates and the use of colonoscopy as a CRC screening test is limited by healthcare costs and the expertise needed to perform the screening. These disadvantages of colonoscopy warrant the development of a new, non-invasive, accurate CRC screening test.

An electronic nose device is an artificial olfactory system that analyses volate organic compounds (VOCs) in exhaled breath. The use of electronic noses has already been assessed as a potential non-invasive diagnostic biomarker test for lung cancer, breast cancer and malignant melanomas. The present study aims to investigate the diagnostic accuracy of exhaled breath analysis with the AeonoseTM (The eNose Company, Zutphen, the Netherlands) to distinguish the breath of patients suspected for CRC (based on a positive fecal immunochemical test (FIT)), who are truly diagnosed with CRC, from patients suspected for CRC in whom this diagnosis is rejected after colonoscopy.

Objectives:

• To investigate the diagnostic accuracy of exhaled breath analysis with the AeonoseTM to distinguish the breath of patients suspected for CRC based on a positive FIT test, who are truly diagnosed with CRC, from patients suspected for CRC in whom this diagnosis is rejected after colonoscopy.
• To investigate the diagnostic accuracy of exhaled breath analysis with the AeonoseTM for other (pre-)malignant colon lesions (e.g. advanced adenomas, non-advanced adenomas, and sessile serrated lesions).
• To assess the acceptance rate of using the AeonoseTM device.

Study design: The present multicenter study will include 1950 FIT-positive patients. The study will be conducted in seven hospitals in the Netherlands. First a database of breath prints will be developed to detect CRC. In this study phase the AeonoseTM will be trained and the database of breath prints will be verified using "leave 10% out" cross validation. After the calibration phase the diagnostic accuracy of AeonoseTM will be assessed in new study patients (external validation).

Study population: Patients between the ages of 55 and 75 years old with a positive FIT-test referred for a colonoscopy procedure.

Main study parameters/endpoints:

• The ability of AeonoseTM to distinguish between patients with and without CRC in a FIT-positive population in terms of sensitivity and specificity.
• The diagnostic accuracy of AeonoseTM for other (pre-)malignant colon lesions.
• Acceptance rate of AeonoseTM

Statistical analysis:

Data on demographic and baseline characteristics will be summarized for continuous variables, in case of normal distribution by mean and standard deviation, and in case of non-normal distribution by median and interquartile range. For discrete variables (eg, race and sex) data will be summarized by proportions (percentages). Differences in baseline characteristics will be determined using independent sample t test, Fisher's exact test or Chi-square test, when appropriate. A 2-sided p-value <0.05 will be considered statistically significant.

The data will be analyzed by an artificial neural network (ANN) to identify data classifiers to extract differences between the patterns in patients by the presence or absence of CRC in biopsies. By analyzing a group of breath prints from patients with and without CRC, individual differences of diet, medications, co-morbidities, and other factors can be filtered out to identify features that distinguish the compounds of patients with CRC. This process continues until a selected level of discrimination is met. Data compression and ANN have been integrated in a proprietary software package (Aethena) of the eNose Company (Zutphen, the Netherlands).

The binary results will be presented in a scatterplot and a receiver operating characteristics curve (ROC-curve). Matthews correlation coefficients will be calculated to measure the quality of binary classifications. Cross-validation of the data will be performed using a leave-10%-out method. A portion of the data is left out to predict the most optimal model.

• Study Type: Interventional
• Enrollment (Actual): 3345
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525
      • Radboud University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients between the ages of 55 and 75 years referred for a colonoscopy procedures after a positive FIT test.

Exclusion Criteria:

• Patients with a history of any type of malignancy (not including basal-cell skin cancer (BCC) and squamous-cell skin cancer (SCC))
• Prior surgical resection of any portion of the colon
• Patients who are unable to perform breathing maneuver needed for Aeonose-analysis of exhaled air

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Adult patients with positive FIT test; Adult patients with a positive FIT-test will breath into an e-nose device for 5 minutes.

Device: Aeonose; An electronic nose device is an artificial olfactory system that analyses volate organic compounds (VOCs) in exhaled breath. The AeonoseTM is a handheld device of 650 gram. A nose clip will be used to prevent the entry of non-filtered air and patients will be instructed to enclose the mouthpiece with their mouth at all times. A measurement cycle lasts for about 15 minutes, of which 5 minutes of in-and exhalation by the patient takes place.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The ability of AeonoseTM to distinguish between patients with and without colorectal cancer in a FIT-positive population in terms of sensitivity and specificity.	Sensitivity and specificity of the Aeonose	1.5 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The diagnostic accuracy of AeonoseTM for other (pre-)malignant colon lesions (e.g. advanced adenomas, non-advanced adenomas, and sessile serrated lesions).	Sensitivity and specificity of the Aeonose	1.5 year
Acceptance rate of AeonoseTM.	Willingness to repeat the procedure and discomfort during test	1.5 year

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2017
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: November 14, 2017
• First Submitted That Met QC Criteria: November 14, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): March 16, 2020
• Last Update Submitted That Met QC Criteria: March 12, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Pathological Conditions, Anatomical; Intestinal Neoplasms; Rectal Diseases; Polyps; Intestinal Polyps; Colorectal Neoplasms; Colonic Polyps
• Other Study ID Numbers: 2017-3704

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No