Total Underwater Colonoscopy (TUC) for Improved Colorectal Cancer Screening: A Randomized Controlled Trial

Colorectal cancer (CRC), the third most diagnosed cancer and second most common cause of cancer death. CRCs develop from precursors like adenomas (about 70% of CRCs) or serrated lesions (SSLs) (about 25-30% of CRCs). Colonoscopy is the cornerstone in CRC screening, in screening programmes often as a work-up examination after a positive primary screening test such as faecal immunochemical test (FIT). Norway and Sweden have recently launched a nationwide faecal haemoglobin CRC screening programmes. Recently, both a Dutch and an Austrian study showed that SSL detection rate (SSLDR) is inversely correlated to CRC at follow-up. Consequently, improved SSLDR can reduce the risk of post-colonoscopy CRC. SSLs are typically located in the right colon. They are flat, with indistinctive boarders, and consequently easily missed or incompletely resected. A Norwegian study showed incomplete resection of 40% of proximal SSLs. The prevalence of SSLs is higher in women than in men, with women being on a threefold risk of developing CRC from SSLs. It seems like post-colonoscopy CRC more often is caused by SSLs than by adenomas. Total underwater colonoscopy (TUC) is a technique replacing conventional CO2 insufflation by water infusion to distend the lumen and visualise the mucosa during withdrawal of the colonoscope and simultaneously removal of water. There are several reasons to advocate TUC:

1. SSLs will be more visible as they "float" on the submucosa and contract into the lumen, while full distension by gas stretches the mucosa, making detection of flat lesions more difficult.
2. Water works like a magnifying lens, making detection and detailed characterisation of lesions easier.
3. uEMR is eased.
4. Improved bowel cleansing

The goal of this clinical trial is to compare colonoscopy outcomes for standard gas (CO2) insufflation and TUC during withdrawal in patients participating in colonoscopy in the Norwegian and Swedish colorectal cancer screening programme after a positive fecal immunochemical test.

The overarching research questions of the present trial is whether colonoscopy outcomes are improved when CO2 insufflation is replaced by TUC during withdrawal and whether the new technique reduces the ecological footprint of the colonoscopy examination.

The project has five main hypotheses:

1. TUC is superior to the standard approach (CO2 withdrawal) regarding detection of proximal SSLs.
2. TUC increases the rate of complete resection of lesions >= 10mm.
3. TUC reduces the rate of painful colonoscopies and vasovagal reactions.
4. TUC reduces the health care costs by reduced use of single use accessories and reduced number of redundant colonoscopies to obtain polypfree colon.
5. TUC reduces the carbon footprint by reduced use of single use accessories.

If TUC is superior to gas insufflation, the technique may be implemented rapidly since the technique is easy to learn. This study will increase endoscopy competence at participating centres. The centres are involved in national colonoscopy training programs, so the technique will quickly be passed on to other hospitals and screening centres.

The trial can be linked to three of the Global Goals:

• Good health and well-being: The increased detection and improved complete removal of sessile serrated lesions can subsequently decrease the risk of CRC and CRC mortality during follow-up. TUC will probably reduce the rate of painful procedures and vasovagal reactions and thus increase the acceptance of a screening programme. Consequently, the project can contribute significantly to improve screening effectiveness in Norway and Sweden, particularly in women (women have a higher risk for SSLs and a higher risk of colorectal cancer developing from this type of precursor).
• Gender equality: Women have a similar lifetime risk for CRC as men but less benefit of screening regardless of whether they are screened by sigmoidoscopy, FIT or colonoscopy. The reason is probably missed sessile serrated lesions in the proximal colon. If TUC improves SSLDR and complete lesion resection, this may lead to an equal benefit from CRC screening for women and men. Women have also a higher risk of discomfort and pain during colonoscopy than men. It has been shown that women prefer non-invasive screening modalities, potentially to avoid pain during colonoscopy, even if colonoscopy may be the most beneficial screening method for women. If TUC reduces the rate of painful colonoscopies, it can reduce women's barriers to attend screening.
• Responsible consumption and production: The TUC technique will also reduce the ecological footprint of colonoscopy activity due to reduced consumption of single use accessories and reduced number of colonoscopies to achieve polyp free colon. Furthermore, the cost for the health care system will be substantially reduced.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer; Colorectal Neoplasia; Screening Colonoscopy; Colorectal Cancer Screening; Vasovagal Reaction
• Intervention / Treatment: Procedure: Conventional colonoscopy; Procedure: Total underwater colonoscopy

• Study Type: Interventional
• Enrollment (Estimated): 1070
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anna Lisa Schult, MD, PhD; Phone Number: +47 67 80 94 00; Email: anschu@vestreviken.no
• Study Contact Backup: Name: Thomas de Lange, MD, associate prof; Email: thomas.de.lange@gu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All individuals referred to colonoscopy after a positive FIT screening at the participating screening centres

Exclusion Criteria:

• Individuals with a CRC diagnosis within the last 10 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional colonoscopy (CO2) group; this groups receives conventional colonoscopy with CO2 withdrawal	Procedure: Conventional colonoscopy; one group will be randomized to undergo a conventional colonoscopy with CO2 withdrawal
Experimental: Total underwater colonoscopy (TUC) group; This group receives total underwater colonoscopy	Procedure: Total underwater colonoscopy; one grooup will be randomized to receive a total underwater colonoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proximal sessile serrated lesion detection rate	The proportion of colonoscopies where at least one proximal SSL is detected	when histopathology report is clear, about 4 weeks after colonoscopy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete resection rate for lesions > 10mm	see above	4 weeks after colonoscopy
Rate of painful procedures and vasovagal reactions	se above	during and immediately after colonoscopy
Leakage after colonoscopy	water leakage on the way home after colonoscopy	Questionnaire 1-7 days after colonoscopy
Detection rate for other neoplasia than SSL	see above	about 4 weeks after colonoscopy
Withdrawal time	see above	immediately after colonoscopy
Total procedure time	see above	immediately after colonoscopy
Bowel cleansing quality	with help of BBPS	immediately after colonoscopy
Complications	Significant bleedings and perforations	within 30 days after colonoscopy
Number of colonoscopies to achieve polyp free colon	see above	after last colonoscopy per patient
Single use accessories for the procedure	number of single use accesoires per colonoscopy	immediately after colonoscopy

Collaborators and Investigators

• Sponsor: Vestre Viken Hospital Trust
• Collaborators: Ullevaal University Hospital; Ostfold Hospital Trust; Sahlgrenska University Hospital, Sweden

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 20, 2024
• First Submitted That Met QC Criteria: March 20, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: colorectal cancer screening; screening colonoscopy; underwater colonoscopy
• Additional Relevant MeSH Terms: Digestive System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neurologic Manifestations; Neurobehavioral Manifestations; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Autonomic Nervous System Diseases; Unconsciousness; Consciousness Disorders; Primary Dysautonomias; Orthostatic Intolerance; Syncope; Colorectal Neoplasms; Syncope, Vasovagal
• Other Study ID Numbers: TotalUnderwater_REK577567

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Access Criteria: Access to research data for external investigators, or use outside of the current protocol, will require approval from the Norwegian Regional Committee for Medical and Health Research Ethic. Research data are not openly available because of the principles and conditions set out in articles 6[1] (e) and 9 [2] (j) of the General Data Protection Regulation (GDPR).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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