ENDCaP-C test accuracy study

Plain English Summary

Background and study aims
Ulcerative colitis (UC) is a long-term condition where the colon and rectum become inflamed. It affects over 30,000 patients in the UK and patients with long-term UC are at an increased risk of developing bowel cancer. Timely recognition of the development of cancer is vital in order to improve outcome for patients. Currently in the UK patients undergo regular and thorough surveillance of the colon to look for the early signs of cancer. Unfortunately this is not adequate and the mortality from late-detected colitis-associated cancers remains high. The main aim of this study is to evaluate the ability of a new diagnostic test to detect patients at high risk of developing colon cancer compared to histology. The test is based on determining whether certain genes that protect against the development of cancer have been inactivated and if effective, could result in a significant change in practice.

Who can participate?
This study aims to recruit up to 1000 patients across NHS hospitals in the UK that have active long-term inflammatory bowel disease endoscopic surveillance programmes. Eligible patients will have UC (either for at least 10 years with extensive disease, or also have primary sclerosing cholangitis), will be on the surveillance programme and undergoing a routine colonoscopy during the study period, have no previous history of colorectal cancer and meet the rest of the rest of the eligibility criteria.

What does the study involve?
All patients will undergo a routine surveillance colonoscopy. In addition to the routine biopsies, an additional five biopsies will be taken. If cancer or the early stages of cancer are detected, then the patient will be offered surgery. Patients for which the new test detects cancer but histology does not, will undergo a repeat colonoscopy at 4 to 12 months. Patients will be followed up through routinely collected data sources, to include, for example, cancer development and long-term survival.

What are the possible benefits and risks of participating?
There may be no direct benefit in taking part in this study, however, participants may benefit from that any pre-cancer changes will be detected early which would ensure that treatments could be started earlier. It has been shown that starting treatment earlier is often more effective. The study may involve an extra colonoscopy between 6 and 9 months after entry into the study. This will involve standard bowel preparation (including laxatives or an enema). A sedative and pain killers may also be given during the colonoscopy. The procedure will be of roughly the same duration as the initial colonoscopy. There is a very small risk (a 1 in 1000 chance) with colonoscopy of bowel perforation or bleeding. If this happened, an operation would be required to repair the hole. At the second colonoscopy you will also be asked to provide a stool sample and to collect a small blood sample.

Where is the study run from?
University of Birmingham (UK)

When is the study starting and how long is it expected to run for?
From November 2014 to May 2018

Who is funding the study?
NIHR Efficacy and Mechanism Evaluation (UK)

Who is the main contact?
Dr Steve Johnson
As of 10/02/2017: Laura Magill

Study website

http://www.birmingham.ac.uk/ENDCaP-C

Type

Scientific

Contact name

Dr Laura Magill

ORCID ID

Contact details

Birmingham Clinical Trials Unit
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

EudraCT/CTIS number

IRAS number

ClinicalTrials.gov number

Protocol/serial number

17739

Scientific title

Enhanced Neoplasia Detection and Cancer Prevention in Chronic Colitis (ENDCaP-C): a multicentre test accuracy study

Acronym

ENDCaP-C

Study hypothesis

The main aim of this study is to evaluate the ability of a new diagnostic test to detect patients at high risk of developing colon cancer compared to histology.

Ethics approval(s)

First MREC approval date 30/10/2014, ref: 14/LO/1842

Study design

Non-randomised; Observational; Design type: Cohort study

Primary study design

Observational

Secondary study design

Cohort study

Study setting(s)

Hospital

Study type

Diagnostic

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Topic: Gastroenterology; Subtopic: Gastroenterology; Disease: All Gastroenterology

Intervention

Current interventions as of 21/05/2018:
Colonoscopy and biopsy: patients will have five biopsy samples taken at their routine surveillance colonoscopy. Biopsy samples will be histologically analysed and methylation status will be determined.

Patients that have a positive methylation test but negative histology will undergo a second colonoscopy at 4-12 months and an additional five biopsy samples will be taken. Histology and methylation status will be determined.

A selection of patients that have a negative methylation test but negative histology will undergo a second colonoscopy at 4-12 months and five biopsy samples will be taken. Histology and methylation status will be determined.

Study Entry: Registration only


Previous interventions:
Colonoscopy and biopsy: patients will have five biopsy samples taken at their routine surveillance colonoscopy. Biopsy samples will be histologically analysed and methylation status will be determined.

Patients that have a positive methylation test but negative histology will undergo a second colonoscopy at 6 months and an additional five biopsy samples will be taken. Histology and methylation status will be determined.

Added 10/02/2017: A selection of patients that have a negative methylation test but negative histology will undergo a second colonoscopy at 6-9 months and five biopsy samples will be taken. Histology and methylation status will be determined.

Study Entry: Registration only

Intervention type

Procedure/Surgery

Primary outcome measure

Current outcome measures as of 21/05/2018:
1. The presence of dysplasia in a mucosal biopsy taken at follow up colonoscopy at 4-12 months
2. The presence of hypermethylation and dysplasia in a mucosal biopsy taken at follow up colonoscopy at 4-12 months

Previous outcome measures as of 10/02/2017:
1. The presence of dysplasia in a mucosal biopsy taken at follow up colonoscopy at 6-9 months
2. The presence of hypermethylation and dysplasia in a mucosal biopsy taken at follow up colonoscopy at 6-9 months

Previous primary outcome measures:
1. The occurrence of dysplasia in mucosal biopsies taken at follow-up colonoscopy at 4-6 months in patients demonstrating hypermethylation (the positive predictive value)
2. The ability of hypermethylation to discriminate between patients with and without dysplasia in mucosal biopsies taken at follow up colonoscopy at 4-6 months (the diagnostic odds ratio)

Secondary outcome measures

Current secondary outcome measure as of 10/02/2017:
Complications from colonoscopy

Previous outcome measures:
1. Correlation of dysplasia in mucosal biopsies with the presence of significant hypermethylation in nondysplastic biopsies taken at the same procedure
2. Correlation of dysplasia with hypermethylation in the same biopsy
3. Correlation of methylation in biopsies from initial and reference colonoscopy
4. Complications from colonoscopy

Overall study start date

13/11/2014

Overall study end date

31/05/2018

Reason abandoned (if study stopped)

Participant inclusion criteria

Current inclusion criteria as of 21/05/2018:
1. Diagnosis of chronic ulcerative colitis with symptoms for over 10 years or diagnosis of primary sclerosing cholangitis (PSC)
2. On the surveillance programme and undergoing a routine colonoscopy during the study period
3. Willing to accept the possibility of an additional colonoscopy between 4 months and 12 months
4. No previous history of colorectal cancer
5. Aged 18 years or over
6. Be able and willing to provide written informed consent for the study

Previous inclusion criteria:
1. Diagnosis of chronic ulcerative colitis of over 10 years duration and disease beyond the splenic flexure or known primary sclerosing cholangitis
2. Scheduled for surveillance colonoscopy during study period
3. Willing to accept the possibility of an additional colonoscopy between 6 months and 9 months
4. No previous history of colorectal cancer
5. Aged 18 years or over
6. Be able and willing to provide written informed consent for the study

Participant type(s)

Patient

Age group

Adult

Lower age limit

18 Years

Sex

Both

Target number of participants

Planned Sample Size: 1000; UK Sample Size: 1000

Total final enrolment

818

Participant exclusion criteria

Current exclusion criteria as of 21/05/2018:
1. Patients with fulminant colitis (if not PSC)
2. Bowel obstruction
3. Patients for whom it is not possible to undergo complete colonoscopies
4. Patients with proctitis only
5. Crohn's colitis patients (if no PSC)
6. Patients with unclassified IBD (if no PSC)
7. Patients with microscopic colitis (if no PSC)
8. Unable to give written informed consent
9. Aged under 18 years

Previous exclusion criteria:
1. Patients with fulminant colitis
2. Bowel obstruction
3. Patients in whom it is not possible to do complete colonoscopies
4. Patients with proctitis only
5. Crohn's colitis patients
6. Patients with unclassified IBD
7. Patients with microscopic colitis
8. Unable to give written informed consent
9. Less than 18 years of age

Recruitment start date

13/11/2014

Recruitment end date

31/03/2017

Countries of recruitment

England, United Kingdom

Study participating centre

Queen Elizabeth Hospital Birmingham
B15 2TH
United Kingdom

Study participating centre

Heartlands Hospital
B9 5SS
United Kingdom

Study participating centre

New Cross Hospital
WV10 0QP
United Kingdom

Study participating centre

Russells Hall Hospital
DY1 2HQ
United Kingdom

Study participating centre

Manor Hospital
WS2 9PS
United Kingdom

Study participating centre

City Hospital, Birmingham
B18 7QH
United Kingdom

Study participating centre

St Mark's Hospital
HA1 3UJ
United Kingdom

Study participating centre

John Radcliffe Hospital
OX3 9DU
United Kingdom

Study participating centre

St James’s University Hospital
LS9 7TF
United Kingdom

Study participating centre

Royal Liverpool University Hospital
L7 8XP
United Kingdom

Study participating centre

Addenbrooke’s Hospital
CB2 0QQ
United Kingdom

Study participating centre

Leicester General Hospital
LE5 4PW
United Kingdom

Study participating centre

Salford Royal Hospital
M6 8HD
United Kingdom

Study participating centre

Blackpool Victoria Hospital
FY3 8NR
United Kingdom

Study participating centre

Bournemouth Royal Hospital
BH7 7DW
United Kingdom

Study participating centre

Royal United Hospital Bath
BA1 3NG
United Kingdom

Study participating centre

West Middlesex University Hospital
TW7 6AF
United Kingdom

Study participating centre

Basingstoke and North Hampshire Hospital
RG24 9NA
United Kingdom

Study participating centre

Queen Alexandra Hospital
PO6 3LY
United Kingdom

Study participating centre

St Mary's Hospital, Isle of Wight
PO30 5TG
United Kingdom

Study participating centre

Basildon University Hospital
Basildon
SS16 5NL
United Kingdom

Study participating centre

Whipps Cross University Hospital
London
E11 1NR
United Kingdom

Study participating centre

James Cook University Hospital
Middlesbrough
TS4 3BW
United Kingdom

Study participating centre

Hull Royal Infirmary
Hull
HU3 2JZ
United Kingdom

Study participating centre

Princess Alexandra Hospital
Harlow
CM20 1QX
United Kingdom

Study participating centre

North Tyneside General Hospital
North Shields
NE29 8NH
United Kingdom

Study participating centre

Darlington Memorial Hospital
Darlington
DL3 6HX
United Kingdom

Study participating centre

Kettering General Hospital
Kettering
NN16 8UZ
United Kingdom

Study participating centre

King's Mill Hospital
Sutton-in-Ashfield
NG17 4JL
United Kingdom

Study participating centre

Luton and Dunstable University Hospital
Luton
LU4 0DZ
United Kingdom

Study participating centre

St Mary's Hospital (Paddington)
London
W2 1NY
United Kingdom

Study participating centre

Queen Elizabeth Hospital (Gateshead)
Gateshead
NE9 6SX
United Kingdom

Organisation

University of Birmingham

Sponsor details

Edgbaston
Birmingham
B15 2TT
England
United Kingdom
-
Researchgovernance@Contacts.bham.ac.uk

Sponsor type

University/education

Website

www.birmingham.ac.uk

ROR

https://ror.org/03angcq70

Funder type

Government

Funder name

NIHR Efficacy and Mechanism Evaluation; Grant Codes: EME/11/100/29

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Publication and dissemination plan

A final report will be submitted for publication in the NIHR Journals Library, as required by the contract for funding for the trial. It is also intended that papers on aspects of the study will be will be submitted to high-impact peer reviewed journals.

Intention to publish date

31/05/2019

Individual participant data (IPD) sharing plan

All data requests should be submitted to the Dr Laura Magill (e.l.magill@bham.ac.uk). Access to available anonymised data may be granted following review.

IPD sharing plan summary

Available on request

Study outputs