Lynch syndrome research registry pilot study
| ISRCTN | ISRCTN14826039 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14826039 |
| IRAS number | 295605 |
| Secondary identifying numbers | 22IC7518, IRAS 295605, CPMS 52834 |
- Submission date
- 05/04/2022
- Registration date
- 08/04/2022
- Last edited
- 07/03/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English Summary
Background and study aims
Lynch Syndrome (LS) is an inherited disorder that is associated with an increased risk of several cancers, particularly bowel cancer, as well as cancer of the womb. In the UK, there are only 6,000 known LS patients, however, it is estimated that there are about 176,000 undiagnosed cases. Given their high risk of bowel cancer, these patients require close monitoring, also known as ‘surveillance’, by colonoscopy - a thin tube with a camera on one end which is used to examine the bowel lining.
Despite national guidelines, the management of LS patients is not well-organised and varies significantly throughout the UK, so many of these patients are not getting the surveillance they need to protect against bowel cancer. To address this variability and to support the national guidelines, several experts in the field have called for a national registry to ensure that all LS patients have access to the timely surveillance they need.
In this study the researchers will develop an LS registry with multiple aims. It will be used to review and improve how LS patients are managed; it will provide data to better support the national screening programme's upcoming role in taking on and managing LS surveillance; and it will provide a unique resource to conduct and support future research into LS.
Who can participate:
LS patients who have previously taken part in the Cancer Prevention Project 3 (CaPP3) trial will be recruited from five sites in England over 9 months.
What does the study involve:
This small-scale initial study, known as a pilot study, will help to answer several important research questions around how LS patients are currently managed, as well as assisting with optimising the data collection process and functionality of the registry for both users and researchers.
Participation will involve completing and returning a baseline health questionnaire, followed by collecting surveillance data at the local hospital with additional data provided by NHS Digital. Data will be held on a secure and confidential database and in accordance with GDPR and Data Protection legislation. Further information will be available at the study website (https://lynchregistry.org.uk/) once the study is open to recruitment.
What are the possible risks and benefits of participating?
There are no risks of physical harm associated with taking part in this study. However, as the registry will be storing some personal information, there is a risk of a breach of confidentiality. The risks stemming from a data breach include; patient distress or loss of patient confidence and fraud by way of identity theft. To minimise the possibility of this occurring, several policies and procedures are in place to help protect participant information and to ensure that any personal information that could identify individuals remains strictly confidential. A data security policy is in place detailing precautions for safe operation such as encryption, access restrictions, security audits and secure software development practices. In the event that there is a breach of confidentiality, all participants will be notified.
There may not be an immediate direct benefit from joining the registry pilot study, but the information we get might help improve the treatment of people with Lynch Syndrome. As the national registry eventually becomes more established Lynch syndrome patients will benefit by being offered regular screening examinations, in line with the national guidelines. Additionally, the national registry will help to raise awareness of Lynch syndrome amongst clinical teams and promote future research projects and collaborations.
Where is the study run from?
Imperial College London (UK)
When is the study starting and how long is it expected to run for?
April 2020 to March 2026
Who is funding the study?
1. Cancer Research UK
2. 40tude (UK)
Who is the main contact?
Prof. Amanda Cross
amanda.cross@imperial.ac.uk
Contact information
Principal Investigator
Room 505
Imperial College London
St Mary's Campus
Norfolk Place
London
W2 1PG
United Kingdom
 ORCID ID |
0000-0002-0893-2377 |
|---|---|
| Phone | +44 (0)20 7594 3401 |
| amanda.cross@imperial.ac.uk |
Study information
| Study design | Multicentre observational questionnaire-based pilot study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Pilot study |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Surveillance for individuals at high-risk of colorectal cancer – using Lynch Syndrome patients as a model |
| Study hypothesis | Lynch Syndrome (LS) is a hereditary cancer syndrome with a population prevalence of between 1 in 125 and 1i n 400 people. LS is especially associated with an elevated colorectal cancer (CRC) and endometrial cancer risk, but also an increased risk of others such as ovarian, gastric and hepatobiliary cancers. LS arises from germline mutations in mismatch repair genes MLH1, MSH2, MSH6 and PMS2, or also EPCAM, deletions within which result in aberrant expression of MSH2. The lifetime CRC risk associated with LS is as high as 80% without surveillance. LS is, however, ‘under-recognised, under-diagnosed and under-managed’, as highlighted in a letter to the British Medical Journal from numerous experts in the field. In the United Kingdom (UK), there are only 6000 known LS patients, however, it is estimated that there are ~176,000 undiagnosed cases. To address this, the National Institute for Health and Care Excellence (NICE) issued new guidelines in 2017 recommending universal testing for LS in all newly diagnosed CRCs. Although this will improve LS diagnosis, urgent improvements are needed in other aspects of LS patient care. NICE guidelines have also highlighted that testing for LS in people diagnosed with endometrial cancer is currently not often done or may only be done for people with an identified risk factor for LS; this could be age at diagnosis or a family history of LS-related cancers. The guidelines recommend undertaking IHC of MMR proteins in all cases of endometrial cancer. Given their high lifetime CRC risk, LS patients should undergo colonoscopy surveillance, which has been associated with a 72% reduction in CRC mortality and a 10-year survival of 90% in those diagnosed with CRC. National guidelines recommend that LS patients undergo colonoscopy surveillance every two years. The responsibility for surveillance of LS patients currently lies with local healthcare providers and, despite these national guidelines, the management of these patients varies significantly across the UK. A national survey reported a widespread perception amongst gastroenterologists, surgeons and oncologists that LS patients were being managed by ‘somebody else’. There is also concern about the robustness and timeliness of the surveillance recall system; few hospitals, for example, have an organised method of providing LS patients with the recommended surveillance. The recent NICE guidelines for CRC tumour testing will increase the number of LS patients identified, which will further exacerbate the need for efficient and well-organised surveillance procedures. It has recently been agreed that the national Bowel Cancer Screening Programme (BCSP) will eventually be taking on the management of LS patient colonoscopy surveillance in England, although this is still likely to take several years before it is fully implemented. Similarly for endometrial cancer, as more LS patients are identified, there may be a growing need for surveillance for this cancer; however, there is a lack of data on the best management of these patients and indeed whether surveillance in these patients is effective. A national registry of LS patients is essential to ensure that LS patients have nationally coordinated care, which will begin to reduce the variation in access to colonoscopy services across the country. The registry will allow healthcare providers access to coordinated assistance to adequately monitor and standardise the frequency of check-ups in line with the national guidelines for all LS patients. Appropriate surveillance consistent with the national guidelines is beneficial for this group of high-risk individuals as surveillance is associated with reduced CRC mortality. The registry will ultimately create a unique resource to conduct and support future research into LS and the associated risk of cancer, including CRC, endometrial and other LS-related cancers, and can also be used as a model for the management of other high-risk conditions. Research questions: 1. How can we optimise the data collection process and functionality of the registry database for both users and researchers? 2. What would be required to better support the national BCSP and their upcoming role in taking on and managing LS surveillance? 3. What proportion of the registry pilot data collected directly from participants and local sites can be provided by the National Disease Registration Service (NDRS) and NHS Digital on a national scale? 4. Can we capture colonoscopy quality assurance data and ascertain disease-specific colonoscopic quality indicators in LS patients? 5. What proportion of LS patients attend colonoscopy surveillance every 2 years? 6. What proportion of LS patients have been tested for Helicobacter pylori (HP) - an important risk factor in the development of gastrointestinal cancers? 7. What options are appropriate for the gynaecological management of female LS patients, particularly when considering patients with PMS2 pathogenic variants? 8. What proportion of LS patients have had a cancer diagnosis? 9. What proportion of LS patients are taking aspirin, why are they taking it and at what dosage or frequency? |
| Ethics approval(s) | Approved 27/05/2022, Newcastle & North Tyneside Research Ethics Committee (NHS BT Blood Donor Centre, Holland Drive, Newcastle upon Tyne, Tyne and Wear, NE2 4NQ; +44 (0)207 104 8171; newcastlenorthtyneside2.rec@hra.nhs.uk), ref: 22/NE/0087 |
| Condition | Cancer in patients with a confirmed Lynch Syndrome diagnosis |
| Intervention | A baseline health questionnaire and surveillance data will be collected, with additional data provided by NHS Digital. |
| Intervention type | Other |
| Primary outcome measure | Successful collection of baseline and surveillance data for consented participants and linkage with NDRS data at 9 months |
| Secondary outcome measures | Frequencies and proportions assessed from data successfully collected under the primary outcome measure at 9 months, including data on those attending colonoscopy or gynaecological surveillance, tested for Helicobacter pylori, presymptomatic and those taking aspirin and at what dose/frequency (see research questions) |
| Overall study start date | 01/04/2020 |
| Overall study end date | 01/03/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 300 |
| Total final enrolment | 257 |
| Participant inclusion criteria | 1. English participants with a confirmed genetic Lynch Syndrome diagnosis 2. Previously taken part in the CaPP3 trial 3. Consented to be contacted about participation in a national Lynch Syndrome Registry |
| Participant exclusion criteria | CaPP3 participants who have not agreed to be contacted about registry participation |
| Recruitment start date | 18/11/2022 |
| Recruitment end date | 07/12/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Watford Road
Harrow
HA1 3UJ
United Kingdom
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Oxford Road
Manchester
M13 9WL
United Kingdom
Birmingham
B4 6NH
United Kingdom
Sponsor information
University/education
Clinical Research Governance Office
G02
Sir Alexander Fleming Building
South Kensington Campus
London
SW7 2AZ
England
United Kingdom
| Phone | +44 (0)20 7594 9480 |
|---|---|
| rgit@imperial.ac.uk | |
| Website | http://www.imperial.ac.uk/ |
"ROR" |
https://ror.org/041kmwe10 |
Funders
Funder type
Charity
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/10/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | Any research results from the registry will be displayed on the ‘research’ page at https://lynchregistry.org.uk/. Research results will be presented to the research community and service providers in scientific literature and presented at national and international scientific conferences, clinical meetings and patient conferences. |
| IPD sharing plan | Individual registry participants will not be identifiable from any reports or publications placed in the public domain. In the future, anonymised information from the Lynch syndrome registry pilot study may also be used to support other studies in the UK, Europe and outside of the European Economic Area, that aim to conduct further research to improve care for Lynch syndrome patients, but only if participants give specific consent for this. The use of any information in future studies will require participant consent and the approval of the Lynch syndrome registry pilot study steering committee. Further information about approved research studies will be available at https://www.lynchregistry.org.uk. Participants can choose on the consent form if they would like their information to be used to support future research studies and if they would like to be contacted about taking part in any future research studies. If participants choose to later take part in a national registry or other studies, they will be asked to consent separately for these. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
07/03/2025: The overall end date was changed from 01/03/2025 to 01/03/2026.
10/10/2024: The following changes were made to the trial record:
1. The overall end date was changed from 31/03/2024 to 01/03/2025.
2. The intention to publish date was changed from 01/10/2024 to 01/10/2025.
01/03/2024: The following changes were made to the study record:
1. The target number of participants was changed from 400 to 300.
2. Total final enrolment added.
12/12/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/12/2023 to 07/12/2023.
2. The overall end date was changed from 01/03/2024 to 31/03/2024.
3. The intention to publish date was changed from 01/07/2024 to 01/10/2024.
22/06/2023: The following changes were made:
1. The overall trial end date has been changed from 01/10/2023 to 01/03/2024 and the plain English summary has been updated to reflect this change.
2. The recruitment end date has been changed from 01/09/2023 to 01/12/2023.
3. Leeds Teaching Hospitals NHS Trust was removed from the study participating centres
02/12/2022: The recruitment start date was changed from 14/11/2022 to 18/11/2022.
04/10/2022: The following changes were made to the trial record:
1. The recruitment start date has been changed from 01/10/2022 to 14/11/2022.
2. The recruitment end date has been changed from 01/07/2023 to 01/09/2023.
07/07/2022: The following changes have been made:
1. The recruitment start date has been changed from 01/07/2022 to 01/10/2022.
2. The recruitment end date has been changed from 01/04/2023 to 01/07/2023.
3. The overall trial end date has been changed from 01/07/2023 to 01/10/2023 and the plain English summary has been updated to reflect this change.
4. The ethics approval has been added.
05/05/2022: Internal review.
06/04/2022: Trial's existence confirmed by 40tude.
