Saliva to predict risk of disease using transcriptomics and epigenetics
| ISRCTN | ISRCTN11921553 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11921553 |
| IRAS number | 217388 |
| Secondary identifying numbers | IRAS 217388 |
- Submission date
- 15/09/2017
- Registration date
- 04/10/2017
- Last edited
- 05/11/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
There are numerous lifestyle-altering diseases in the UK for which patients undergo multiple invasive tests before they can be properly diagnosed. These tests are often uncomfortable and inconvenient for patients, in addition to being very costly for the National Health Service (NHS). They typically involve a degree of risk to patients (e.g. bleeding and bowel rupture during endoscopy, or harmful radiation exposure from CT scanning). Many of these tests also tend to have normal results, since only a small fraction of patients are eventually diagnosed with the disease being sought. The aim of this study is to analyse symptoms, risk factors and genetic changes detected in saliva samples to predict patients’ risk of developing diseases.
Who can participate?
Patients aged over 18 who are already known to have oesophageal or colorectal disease including Crohn's disease, and patients who are awaiting tests to diagnose or exclude these diseases.
What does the study involve?
Participants complete a questionnaire to obtain information regarding their symptoms and risk factors for the disease. Saliva and blood samples are collected and, when appropriate, blood and tissue samples are taken during any investigations that they are already scheduled to undergo as part of their treatment process. No additional procedures or interventions are performed on these patients, and their clinical treatment is not affected in any way. Genetic analysis is performed on these samples to see if the characteristics of the patients’ saliva in combination with symptoms and other risk factors can accurately predict their disease. The saliva test results are compared with the blood and, where possible, tissue test results.
What are the possible benefits and risks of participating?
The results may help to create a cheap, portable and quick bedside test that uses patients’ saliva to predict their risk of disease, so that only high-risk patients will in future need to undergo invasive investigations. This will save the NHS and other healthcare systems worldwide significant amounts of money, while saving patients across the world time, inconvenience and reducing their risk of complications from unnecessary investigations.
Where is the study run from?
1. University College London (UK)
2. University College London Hospitals NHS Trust (UK)
3. Guy's and St Thomas' NHS Foundation Trust (UK)
4. Lister Hospital (UK)
5. Frimley Park Hospital (UK)
6. Wexham Park Hospital (UK)
7. Western Sussex Hospitals NHS Foundation Trust (UK)
8. Princess Alexandra Hospital (UK)
9. Royal Albert Edward Infirmary (UK)
10. Royal Surrey County Hospital (UK)
11. Shrewsbury and Telford Hospital NHS Trust (UK)
12. UK IIBD Bioresource
When is the study starting and how long is it expected to run for?
April 2017 to March 2023
Who is funding the study?
1. Rosetrees Trust (UK)
2. CORE Digestive Disorders Foundation (UK)
3. Helmsley Charitable Trust (USA)
Who is the main contact?
Prof. Laurence Lovat
Contact information
Scientific
Research Department of Targeted Intervention
Division of Surgery & Interventional Science
University College London
Floor 3, Charles Bell House
43-45 Foley Street
London
W1W 7TS
United Kingdom
Study information
| Study design | Observational basic science study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Case-control study |
| Study setting(s) | Hospital |
| Study type | Screening |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Saliva to predict risk of disease using transcriptomics and epigenetics (SPIT): an observational study |
| Study acronym | SPIT |
| Study objectives | There are numerous lifestyle-altering diseases in the UK for which patients undergo multiple invasive tests before they can be properly diagnosed. These tests are often uncomfortable and inconvenient for patients, in addition to being very costly for the National Health Service (NHS). They typically involve a degree of risk to patients (e.g. bleeding and bowel rupture during endoscopy; or harmful radiation exposure from CT scanning). Many of these tests also tend to have normal results, since only a small fraction of patients are eventually diagnosed with the disease being sought. This study will focus on using analysis of symptoms, risk factors and genetic changes detected in saliva samples to predict patients’ risk of developing diseases. |
| Ethics approval(s) | West Midlands - Coventry & Warwickshire Research Ethics Committee, 28/02/2017, ref: 17/WM/0079 |
| Health condition(s) or problem(s) studied | Oesophageal cancer, colorectal cancer, Crohn's disease |
| Intervention | A ‘symptom and risk factor’ questionnaire will be developed based on known symptoms and risk factors for the disease being studied. Saliva will be collected from patients from the identified groups representing the disease profiles being studied and appropriate control subjects and analysed for epigenetic and transcriptomic biomarkers. Matched blood samples may also be collected from patients to demonstrate whether the salivary epigenetic and transcriptomic findings match those in the blood. Where patients are already undergoing invasive tests, matched tissue samples from normal and diseased tissue may be collected to demonstrate whether the salivary epigenetic and transcriptomic findings match those in the tissue. Bioinformatics combined with novel artificial intelligence techniques will be used to analyse the samples to identify highly accurate biomarker profiles to predict the presence of both disease and disease risk. |
| Intervention type | Other |
| Primary outcome measure | Epigenetic and transcriptomic biomarkers, measured using next generation sequencing of saliva/blood/tissue samples collected at single study visit |
| Secondary outcome measures | Disease symptoms and risk factors, measured using questionnaire at single study visit |
| Overall study start date | 06/04/2017 |
| Completion date | 01/10/2023 |
Eligibility
| Participant type(s) | Mixed |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 2000 |
| Key inclusion criteria | Current participant inclusion criteria as of 25/08/2021: For the initial study of oesophageal disease, both current and new patients identified as having oesophageal disease (e.g. Barrett’s oesophagus, oesophageal cancer) will be recruited together with those being referred along the 2-week-wait cancer-target pathway. Patients without oesophageal disease attending for a clinically indicated endoscopy may be recruited as controls. For the initial study of colorectal disease, patients will be recruited from the National Bowel Cancer Screening Programme, as well as from other patients with colorectal disease attending for colonoscopy. Patients without colorectal disease attending for a clinically indicated colonoscopy may be recruited as controls. For patients with Crohn's disease, both the UK IBD Bioresource and participating centres will contact patients inviting them to sign up for the study online. Previous participant inclusion criteria: For the initial study of oesophageal disease, both current and new patients identified as having oesophageal disease (e.g. Barrett’s oesophagus, oesophageal cancer) will be recruited together with those being referred along the 2-week-wait cancer-target pathway. Patients without oesophageal disease attending for a clinically indicated endoscopy may be recruited as controls. For the initial study of colorectal disease, patients will be recruited from the National Bowel Cancer Screening Programme, as well as from other patients with colorectal disease attending for colonoscopy. Patients without colorectal disease attending for a clinically indicated colonoscopy may be recruited as controls. |
| Key exclusion criteria | Current participant exclusion criteria as of 25/08/2021: 1. Patients who are unable to undergo definitive investigations such as colonoscopy or surgery as a definitive pathological diagnosis will not be achievable in such instances 2. Patients who are unable to give informed consent in English, or in the presence of an English translator 3. Pregnant women 4. Patients under the age of 18 years Previous participant exclusion criteria: 1. Patients who are unable to undergo definitive investigations such as colonoscopy or surgery as a definitive pathological diagnosis will not be achievable in such instances 2. Patients who are unable to give informed consent in English, or in the presence of an English translator 3. Pregnant women 4. Patients under the age of 21 years |
| Date of first enrolment | 06/04/2017 |
| Date of final enrolment | 01/03/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Sponsor information
University/education
Joint Research Office
1st Floor, Maple House – Suite B
149 Tottenham Court Road
London
W1T 7DN
England
United Kingdom
"ROR" |
https://ror.org/02jx3x895 |
|---|
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Teresa Rosenbaum Golden Charitable Trust, Rosetrees
- Location
- United Kingdom
No information available
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Helmsley Charitable Trust, The Leona M. and Harry B. Helmsley Charitable Trust, Leona M. & Harry B. Helmsley Charitable Trust, The Helmsley Charitable Trust
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/10/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in high-impact peer reviewed journals. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Laurence Lovat. Data will be available after the study ends. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Other publications | 09/03/2020 | 25/11/2020 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 01/01/2024 | 05/11/2024 | Yes | No |
Editorial Notes
05/11/2024: Publication reference added.
25/08/2021: The following changes have been made:
1. The recruitment end date has been changed from 01/08/2019 to 01/03/2023.
2. The overall trial end date has been changed from 01/10/2019 to 01/03/2023.
3. The intention to publish date has been changed from 01/10/2020 to 01/10/2023.
4. A funder has been added.
5. has been updated from "Oesophageal cancer, colorectal cancer" to "Oesophageal cancer, colorectal cancer, Crohn's disease".
6. The participant inclusion criteria have been updated.
7. The participant exclusion criteria have been updated.
8. The trial participating centre "IBD Bioresource" has been added.
9. The plain English summary has been updated to reflect the changes above.
25/11/2020: Publication reference added.
03/09/2019: The scientific contact's details have been updated.
28/08/2018: The contact details were updated and the trial participating centres were added.
