Non-invasive Risk Stratification of CR AMN/SSP (FIT)

Evaluation of Stool and Blood Based Tests for Colorectal Advanced Mucosal Neoplasia

The purpose of this study is to determine the clinical utility of stool and blood methylation tests for detection of advanced mucosal neoplasia (AMN) and sessile serrated polyps (SSP).

Study Overview

• Status: Completed
• Conditions: Adenomatous Polyps
• Intervention / Treatment: Other: blood or stool samples will be collected

Detailed Description

By not only diagnosing colorectal cancer (CRC) at an early stage, but also removing precursor lesions (adenomas), colonoscopy with polypectomy reduces the risk of developing and dying from CRC. Approximately 90% of polyps are less than 10 mm and are easily removed by competent endoscopists. Laterally spreading lesions (LST) and sessile lesions of the colon, also known as advanced mucosal neoplasia (AMN) are underrecognised types of lesions that are more likely to progress to cancer. They include sessile serrated polyps (SSP), an emerging entity of flat polyps with malignant potential. Detection of hemoglobin (a component of blood) in stool is an established validated screening tool for CRC. Its specific role in the prediction of AMN, and particularly SSPs is yet to be defined. Blood tests measuring the level of tumour derived methylated deoxyribonucleic acid (DNA) in blood circulating have been demonstrated to have clinical utility for detection of CRC and AMN. A blood based CRC screening test has the potential to increase compliance. This study aims to determine the clinical utility of stool and blood methylation tests for detection of AMN and SSPs. Stool and blood will be obtained from consenting patients referred for endoscopic removal of known ANM and SSP (study arm) as well as from consenting patients scheduled for colonoscopy screening (control arm). The level of stool hemoglobin and methylated tumour derived DNA in circulation will be measured in the two study groups. Cutoff values will be generated to assess best predictive capability of high risk lesions based on these tests.

• Study Type: Observational
• Enrollment (Actual): 205

Contacts and Locations

• Study Contact: Name: Rebecca Sonson, BN MPH; Phone Number: 59779 0298455555; Email: Rebecca.Sonson@health.nsw.gov.au
• Study Contact Backup: Name: Michael J Bourke, MBBS, FRACP; Phone Number: 59779 98455555; Email: bec2153@gmail.com

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Endoscopy Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

The study population will be comprised of subjects diagnosed with AMN/SSP and subjects scheduled for screening colonoscopy.

Description

Inclusion Criteria:

• Individuals capable and willing of proving satisfactory informed consent
• Individuals with colonic lesions larger than 20mm
• Individuals diagnosed with laterally spreading or sessile polyp morphology
• Individuals schedules for screening colonoscopy and with no prior history of CRC
• Ability and willingness to collect stool sample at home
• Ability and willingness to undergo venepuncture procedure

Exclusion Criteria:

• Individuals not able or unwilling to provide informed consent
• Individuals less than 18 year of age
• Individuals who undergo an incomplete colonoscopy or resection, which raises doubt as to the status of the colon (post-hoc exclusion)
• Individuals with a prior history of CRC
• Individuals with a history of Irritable Bowel Disease (IBD), hereditary nonpolyposis colorectal cancer (HNPCC) or Familial adenomatous polyposis (FAP)
• Individuals with bleeding diathesis
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Normal subjects; blood or stool samples will be collected from people referred for screening colonoscopy	Other: blood or stool samples will be collected; blood or stool samples will be collected
Colorectal cancer; blood or stool samples will be collected from people with colorectal cancer detected at colonoscopy or resection	Other: blood or stool samples will be collected; blood or stool samples will be collected
Polyps <10mm and no high risk features; blood or stool samples will be collected from people with no polyps or low risk polyps (<10mm, no villous component or dysplasia) detected at colonoscopy	Other: blood or stool samples will be collected; blood or stool samples will be collected
Advanced Mucosal Neoplasia; blood or stool samples will be collected from people with AMN detected at resection
Sessile Serrated Adenoma; blood or stool samples will be collected from people with SSP detected at resection
non-colorectal neoplastic disease; Participants with disease that is not colorectal neoplasia. Analysis of this cohort is not a primary endpoint but the investigators will report assay positivity in this group on an opportunistic basis. This cohort will include patients diagnosed with, for example, inflammatory bowel disease or extracolonic cancer.	Other: blood or stool samples will be collected; blood or stool samples will be collected

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Demographics	Data to adequately describe demographic situations of each participant.	1 day
Level of methylated DNA in circulation	The process will use an automated extraction procedure incorporating state-of-the-art magnetic silica-coated beads on a QIASymphony (Qiagen). The extracted DNA is bisulphite-converted and further purified (automated on a QIACube HT liquid handler) prior to analyzing 12uL of bis-DNA in a multi-plexed (BCAT1, IKZF1, ACTB (control assay)) real-time PCR for measuring the methylation levels of target amplicons.	5 years
Level of haemoglobin in stool	Suspended stool collected in the HM-JACKarc sampling device will be processed for Hb measurements using commercially available reagents and the bench-top analyser instrument, HM-JACKarc, according to manufacturer recommendation (Kyowa Medex Co Ltd, Japan). Measured haemoglobin concentrations will be reported as ug Hb/g stool. A 20 ug Hb/g stool a cut-off concentration will be used for qualitative reporting.	5 years
Demographics	Data to adequately decribe the clinical situations of each participant.	1 day

Collaborators and Investigators

• Sponsor: Professor Michael Bourke
• Investigators: Principal Investigator: Michael J Bourke, MBBS FRACP, Westmead Hospita

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2016
• Primary Completion (Actual): July 1, 2020
• Study Completion (Actual): July 1, 2021

Study Registration Dates

• First Submitted: June 10, 2015
• First Submitted That Met QC Criteria: June 16, 2015
• First Posted (Estimated): June 19, 2015

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 28, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Sessile serrated polyps; Advanced mucosal neoplasia
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Adenoma; Adenomatous Polyps
• Other Study ID Numbers: HREC2014/9/4.4(4079)