Non-invasive Risk Stratification of CR AMN/SSP

Adenomatous Polyps Clinical Trial

— FIT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02476682
• Other study ID #: HREC2014/9/4.4(4079)
• Status: Completed
• Start date: January 11, 2016
• Est. completion date: July 2021

Study information

• Verified date: June 2023
• Source: Western Sydney Local Health District
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 205
• Est. completion date: July 2021
• Est. primary completion date: July 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenomatous Polyps

Intervention

Other:
• blood or stool samples will be collected
blood or stool samples will be collected

Locations

Country	Name	City	State
Australia	Westmead Endoscopy Unit	Westmead	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Professor Michael Bourke

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Demographics	Data to adequately describe demographic situations of each participant.	1 day
Primary	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
Primary	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
Primary	Demographics	Data to adequately decribe the clinical situations of each participant.	1 day