AFI-targeted confocal endomicroscopy in Barrett's oesophagus

ISRCTN	ISRCTN16366217
DOI	https://doi.org/10.1186/ISRCTN16366217
Secondary identifying numbers	33291

Submission date: 12/06/2017
Registration date: 25/07/2017
Last edited: 23/09/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-a-new-test-to-find-cell-changes-for-people-with-barretts-oesophagus-ace-b

Contact information

Ms Michele Bianchi
Public

MRC Cancer Centre
Hutchison MRC Research Centre
University of Cambridge
Cambridge
CB2 0XZ
United Kingdom

Dr Massimiliano di Pietro
Scientific

MRC Cancer Centre
Hutchison MRC Research Centre
University of Cambridge
Cambridge
CB2 0XZ
United Kingdom

Phone	+44 122 3763994
Email	md460@mrc-cu.cam.ac.uk

Study information

Study design	Randomised; Interventional; Design type: Diagnosis, Imaging
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Cross-over randomised study to evaluate the combination of autofluorescence imaging and confocal laser endomicroscopy to diagnose dysplasia in Barrett’s oesophagus
Study hypothesis	The aim of this study is to test a combination of enhanced endoscopic imaging (autofluorescence imaging and confocal laser endomicroscopy) in combination to molecular tests on tissue samples to allow diagnosis of dysplasia and early cancer in Barrett’s oesophagus.
Ethics approval(s)	East of England - Cambridgeshire and Hertfordshire Research Ethic Committee, 05/04/2017, ref: 16/EE/0554
Condition	Barrett's oesophagus
Intervention	As part of this study, patients referred with flat Barrett’s oesophagus without evidence of visible lesions receive two endoscopies in a randomised order (standard procedure and experimental procedure). Standard procedure: This includes a standard endoscopy with multiple random biopsies according to the Seattle protocol (targeted biopsies on visible lesions + 4 biopsies every 2 cm within the Barrett's oesophagus). The endoscopist is only be allowed to use white light high resolution endoscopy. Experimental procedure: This procedure uses multimodal imaging. The endoscopist uses autofluorescence imaging (AFI) to identify area at risk of dysplasia. These are analysed with Probed-Based Confocal Laser Endomicrosopy (pCLE) to make a real-time optical diagnosis (Barrett’s with or without dysplasia). Two targeted biopsies stored in formalin are then taken for histology and biomarkers from each AFI targeted location. In patients with no AFI positive areas one random location are used for pCLE analysis and molecular biomarkers for every 5cm of maximum extent of the Barrett’s. The biopsies on AFI targeted areas processed for standard histology are used for clinical purpose as well and are part of the final histologic diagnosis and potentially inform treatment as per clinical guidelines. In addition to histological diagnosis, the biopsies taken during the experimental procedure are tested for a panel of 3 molecular biomarkers. After the first study procedure, the patient arecheduled for a second endoscopy 8-12 weeks after with the alternative protocol. With the second procedure the patient completes the study and referred for standard clinical management based on the histopathological result of the biopsies taken during the two study procedures.
Intervention type	Other
Primary outcome measure	The diagnostic accuracy for any grade of dysplasia of pCLE is measured comparing real-time optical diagnosis of dysplasia by pCLE on AFI-positive areas (experimental procedure) with the gold standard histologic diagnosis (overall pathological diagnosis from experimental and standard procedures).
Secondary outcome measures	1. Added value of the use of molecular biomarkers to the optical biopsy for the diagnosis of any grade of dysplasia. This will be measured by testing molecular biomarkers on tissue biopsies. The biomarkers result will be integrated with that of the optical diagnosis and the results will be compared with that of the gold standard histologic diagnosis. 2. Diagnostic accuracy for any grade of dysplasia of a panel of biomarkers performed on AFI-targeted biopsies. This will be measured by testing molecular biomarkers on tissue biopsies and comparing the results with the gold standard histologic diagnosis 3. Time to perform AFI-targeted pCLE vs gold standard (Seattle protocol). This will be measured as time from the beginning to the end of each endoscopic procedure. Standard and experimental procedure time will be compared. 4. Costs to perform AFI-targeted pCLE +/- biomarkers and conventional endoscopic surveillance with Seattle protocol. This will be measured by the costs of a single use of pCLE probe and laboratory costs of molecular biomarkers for the experimental procedure and costs for processing biopsies and costs of pathology time for histologic diagnosis for the standard procedure. 5. Patient-reported experience and outcome measures, including acceptability and anxiety levels. This outcome will be measured using 2 validated questionnaires: a 10-point visual analogue scale (VAS, 0 = worst and 10 = best), filled by participants before and after each procedure and 6-item state-trait anxiety inventory (STAI -6), completed after each procedure.
Overall study start date	02/05/2017
Overall study end date	29/02/2020

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 146; UK Sample Size: 146
Total final enrolment	146
Participant inclusion criteria	1. Able to read, comprehend, and complete the consent form 2. Aged ≥18 3. Diagnosed with dysplastic or non-dysplastic BO at least 2 cm in length if circumferential (C2) or 3 cm if not circumferential (M3)
Participant exclusion criteria	1. Oesophagitis (Los Angeles grade ≥B) 2. Previous oesophagectomy or known oesophageal abnormality (e.g. fistula or severe oesophageal stricture) 3. Previous evidence of oesophageal adenocarcinoma 4. Previous history of endoscopically visible BO-related neoplasia 5. Known allergy to fluorescein 6. Severe or uncontrolled asthma 7. Coagulopathy or anticoagulant/antiplatelet therapy for high risk conditions 8. Active or severe cardiopulmonary disease or decompensated liver disease 9. Pacemaker or other intra-cardiac electric device
Recruitment start date	02/05/2017
Recruitment end date	31/12/2019

Locations

Countries of recruitment

England
United Kingdom

Study participating centres

Cambridge University Hospital

Hills Road
Cambridge
CB2 0QQ
United Kingdom

Nottingham University Hospital

The Queen's Medical Centre Campus
Derby Road
Nottingham
NG7 2UH
United Kingdom

Sponsor information

Cambridge University Hospitals NHS Foundation Trust
Hospital/treatment centre

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom

"ROR"	https://ror.org/04v54gj93

Funders

Funder type

Charity

Cancer Research UK
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date	31/08/2020
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Presentation of final results in international conferences of gastroenterology in 2019. Planned publication in a high-impact peer reviewed journal.
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from from the Chief Investigator, Dr Massimiliano di Pietro [md460@mrc-cu.cam.ac.uk ]

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Plain English results			23/09/2022	No	Yes
HRA research summary			28/06/2023	No	No

Editorial Notes

02/09/2022: Cancer Research UK plain English results link added.
14/01/2020: The following changes have been made:
1. The overall trial end date has been changed from 31/01/2020 to 29/02/2020.
2. The total final enrolment number has been added.
25/09/2019: The recruitment end date was changed from 30/11/2019 to 31/12/2019.
09/09/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/10/2019 to 30/11/2019.
2. The overall trial end date was changed from 31/12/2019 to 31/1/2020.
3. The intention to publish date was changed from 30/06/2020 to 31/8/2020.
05/09/2019: The recruitment end date has been changed from 01/08/2019 to 31/10/2019.
03/04/2019: The condition has been changed from "Specialty: Gastroenterology, Primary sub-specialty: Gastroenterology; UKCRC code/ Disease: Oral and Gastrointestinal/ Other diseases of the digestive system, Cancer/ Malignant neoplasms of digestive organs" to "Barrett's oesophagus" following a request from the NIHR.
15/01/2018: The recruitment end date was changed from 01/10/2018 to 01/08/2019.
13/10/2017: Cancer Help UK lay summary link added to plain English summary field
11/08/2017: Internal review.