ENDCaP-C test accuracy study
| ISRCTN | ISRCTN81826545 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN81826545 |
| Secondary identifying numbers | 17739 |
- Submission date
- 08/01/2015
- Registration date
- 11/05/2015
- Last edited
- 26/01/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
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
Contact information
Scientific
Birmingham Clinical Trials Unit
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
Study information
| 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 |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Enhanced Neoplasia Detection and Cancer Prevention in Chronic Colitis (ENDCaP-C): a multicentre test accuracy study |
| 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 |
| 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 |
Eligibility
| 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 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 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 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
United Kingdom
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SS16 5NL
United Kingdom
E11 1NR
United Kingdom
TS4 3BW
United Kingdom
HU3 2JZ
United Kingdom
CM20 1QX
United Kingdom
NE29 8NH
United Kingdom
DL3 6HX
United Kingdom
NN16 8UZ
United Kingdom
NG17 4JL
United Kingdom
LU4 0DZ
United Kingdom
W2 1NY
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NE9 6SX
United Kingdom
Sponsor information
University/education
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| Researchgovernance@Contacts.bham.ac.uk | |
| Website | www.birmingham.ac.uk |
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 31/05/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| 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. |
| 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. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/01/2021 | 26/01/2021 | Yes | No |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
26/01/2021: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
24/05/2018: The following changes have been made:
1. The publication and dissemination plan has been changed.
2. An intention to publish date has been added.
21/05/2018: The following changes have been made:
1. The interventions have been changed.
2. The primary outcome measures have been changed.
3. The overall trial end date has been changed from 31/12/2017 to 31/05/2018.
4. The participant inclusion criteria have been changed.
5. The participant exclusion criteria have been changed.
6. The plain English summary has been changed to reflect the changes above.
10/02/2017: Overall trial end date changed from 30/04/2016 to 31/12/2017. Recruitment end date changed from 30/04/2016 to 31/03/2017. Alexandra Hospital (UK), Southampton General Hospital (UK) and Norfolk and Norwich University Hospital (UK) were removed as trial participating centres. Basildon University Hospital, Whipps Cross University Hospital, James Cook University Hospital, Hull Royal Infirmary, Princess Alexandra Hospital, North Tyneside General Hospital, Darlington Memorial Hospital, Kettering General Hospital, King's Mill Hospital, Luton and Dunstable University Hospital, St Mary's Hospital (Paddington), Queen Elizabeth Hospital (Gateshead) were added as trial participating centres. Internal review was conducted.
