Investigating the use of a new fluorescent compound to identify pre cancerous and cancerous lesions in the bowel
| ISRCTN | ISRCTN90128107 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN90128107 |
| Secondary identifying numbers | LECTIN Trial |
- Submission date
- 29/07/2016
- Registration date
- 07/04/2017
- Last edited
- 16/01/2018
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
In the UK, over 40,000 patients are diagnosed with colorectal cancer each year1. Colonoscopy is an important diagnostic and therapeutic procedure in the management of colorectal cancer. The gold standard has been white-light endoscopy for screening the general population and for surveillance of patients at high risk of developing cancer. Early detection of colorectal lesions in screening has been shown to reduce colorectal cancer mortality. However, the detection of flat and depressed neoplasms presents a particular challenge. Recent developments to aid the detection and characterisation of dysplastic lesions include chromoendoscopy, narrow band imaging (NBI), auto-fluorescence (AFI) and confocal endomicroscopy. The development of an adjunct tool to specifically identify premalignant colorectal dysplasia and cancer, and to help distinguish between polyps. A key issue during transanal endoscopic microsurgery (TEMS) and endoscopic mucosal resection (EMR) is to determine where the resection margin should be. Based on conventional white light visualisation, it is often difficult to discern where that margin should be, particularly for flat or carpet-like lesions. A fluorescent tool that can highlight dysplastic tissue would therefore allow complete resection of abnormal tissue. Recent developments in molecular imaging include the generation of fluorescent probes. Lectins are specific carbohydrate recognition proteins and have previously been used to identify malignant tissue through changes in glycosylation observed in carcinogenesis. A detailed understanding of the changes in glycoprotein expression and glycosylation patterns that occur during carcinogenesis may help to identify potentially useful markers of dysplasia. Fluorescently labelled lectins therefore have the potential to distinguish dysplasia and cancer from normal mucosa, based on their differential binding. We have identified and used a fluorescently labelled lectin, Wisteria floribunda (WFA) as an adjunct endoscopic tool, which binds to normal mucosa, but not to high grade dysplasia or cancer. This lectin can also distinguish benign hyperplastic polyps (HPs) from pathologically significant polyps, including sessile serrated polyps (SSPs), traditional serrated adenomas (TSAs) and mucinous cancers. Our lectin can also identify areas of dysplasia in freshly resected ulcerative colitis and TEMS specimens. The lectin can be visualised using fluorescence-enabled endoscopes, e.g. ETMI (endoscopic Trimodal Imaging) colonoscopies.
Who can participate?
Adults aged 18 and older who are undergoing endoscopy procedures.
What does the study involve?
Participants who are undergoing endoscopy have their colonoscopy with white light as per standard practice. The fluorescent lectin is applied to any lesions identified with white light and an assessments are made on the fluorescence level. Where no lesions have been identified with white light, the fluorescent lectin is applied to a segment of colon to assess whether the lectin identifies any additional abnormalities. Following this their procedure is completed as per standard practice and the participant returns to recovery. Routine observations will be taken by the nursing staff and any side effects will be reported. Participants undergoing surgery are anaesthetised and positioned as per standard care. The lectin is applied to the lesion prior to excision and an assessment be made on its fluorescence. After excision, images aretaken of the resection margin. The procedure is completed. Following the procedure the surgeon is asked whether they would change the resection margin based on the appearance of the lectin, and this is compared to the histolopathologists reports of the margin. The participant returns to recovery and receive their routine care. All patients have their clinical notes reviewed 30 days post-procedure for any complications.
What are the possible benefits and risks of participating?
The potential benefits of this procedure would be the earlier and clearer identification of tumours and cancers, and to help guide resection margins during polypectomy and surgery. The potential risks would be the possible side effects of application of lectins topically to patient’s colon and rectum, which may include diarrhoea and nausea, and a lengthier examination as a result of using this new technology. The patient population would be patients undergoing endoscopic procedures, including colonoscopy and flexible sigmoidoscopy. We will also include patients undergoing transanal endoscopic microsurgery (TEMS), including robotic assisted procedures. The results of this study will inform future research and practice.
Where is the study run from?
Oxford University Hospital (UK)
When is the study starting and how long is it expected to run for?
July 2016 to January 2019
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
Mr Thomas Barnes (Public)
Contact information
Public
Nuffield Department of Surgery
John Radcliffe Hospital
Headley Way
Oxford
OX3 9DU
United Kingdom
 ORCID ID |
0000-0001-7328-5797 |
|---|
Study information
| Study design | Non-randomised single-arm feasibility study |
|---|---|
| Primary study design | Observational |
| Secondary study design | |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Investigating the use of a fluorescent lectin to identify dysplasia and cancer during endoscopy and surgery |
| Study acronym | LECTIN Trial |
| Study objectives | Fluorescein conjugated wisteria floribunda identifies dysplasia and cancer during colonoscopy and transanal endoscopic microsurgery (TEMS). |
| Ethics approval(s) | Board NRES Committee South Central - Oxford B, 01/07/2016, ref: 14/SC/1250 |
| Health condition(s) or problem(s) studied | Colorectal cancer |
| Intervention | For patients having endoscopy, they will initially have their colonoscopy with white light as is standard practice. The fluorescent lectin is applied to any lesions identified with white light and an assessments are made on the fluorescence level. Where no lesions have been identified with white light, the fluorescent lectin is applied to a segment of colon to assess whether the lectin identifies any additional abnormalities. Following this their procedure is completed as per standard practice and the patient returns to recovery. Routine observations will be taken by the nursing staff and any side effects will be reported. Patients are discharged as per instructed by their clinician. For patients undergoing surgery they are anaesthetised and positioned as per standard care. The lectin is applied to the lesion prior to excision and an assessment be made on its fluorescence. After excision, images are taken of the resection margin. The procedure is completed. Following the procedure the surgeon are asked whether they would change the resection margin based on the appearance of the lectin, this is compared to the histolopathologists reports of the margin. The patient returns to recovery and receive their routine care. All patients have their clinical notes reviewed 30 days post-procedure for any complications. |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | 1. Signal to background ratio after application of lectin is measured using the fluorescence ratio of WFA binding to normal versus dysplastic/early cancer tissue during endoscopic or surgical procedure 2. Detection rate of dysplastic and cancerous lesions compared to white light alone is measured as the number of lesions identified during endoscopic or surgical procedure and calculating the sensitivity and specificity |
| Secondary outcome measures | No secondary outcome measures |
| Overall study start date | 21/08/2014 |
| Completion date | 01/01/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 50 |
| Key inclusion criteria | 1. Participant is willing and able to give informed consent for participation in the study 2. Male or female, aged 18 years or over 3. Patients undergoing endoscopic procedures including colonoscopy and flexible sigmoidoscopy as well as transanal endoscopic microsurgery (TEMS), including robotic assisted TEMS 4. In the investigator’s opinion, is able and willing to comply with all study requirements |
| Key exclusion criteria | 1. Patient who is unable or unwilling to give informed consent 2. Female participant who is pregnant, lactating or planning pregnancy during the course of the trial. If there is an uncertainly regarding whether a woman could be pregnant, then they will be excluded from the study. 3. Patients with known egg allergies, ovalbumin allergy and soya allergies |
| Date of first enrolment | 01/07/2016 |
| Date of final enrolment | 01/01/2019 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Headington
Oxford
OX3 9DU
United Kingdom
Sponsor information
University/education
Joint Research Office
Block 60
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
England
United Kingdom
| Website | https://www.admin.ox.ac.uk/researchsupport/ctrg/ |
|---|---|
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/01/2020 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
16/01/2018: The plain English summary has been added.
16/10/2017: Internal review.
11/10/2017: internal review.
15/09/2017: Internal review.
06/06/2017: Internal review.
