Ori-EGI-02 Exploratory Study
Research type
Research Study
Full title
An Exploratory Study Investigating the Potential of a Rectal Mucus Sample for Development of Biomarker Assays in Subjects with Gastrointestinal Diseases
IRAS ID
263745
Contact name
Jon Lacy-Colson
Contact email
Duration of Study in the UK
5 years, 3 months, 30 days
Research summary
The study aim is to assess whether a rectal mucus sample collected with the OriCol™ Sampling Device can be used in the development of assays with potential clinical utility, facilitating the provision of tests with superior performance to those using other sample types that could improve the management of patients with gastrointestinal disorders.
The OriCol™ Sampling Device collects rectal mucus trans-anally through a proctoscope. Proctoscopic examination is routine for patients being investigated for bowel disease. Rectal mucus is an interesting alternative to stool for analysis of gastrointestinal disease. It is a rich source of exfoliated colonocytes shed from the surface of the colon that move along the bowel in the mucus layer and accumulate in the rectum. There is increased exfoliation in diseases such as colorectal cancer, making the sample ideally suited for the analysis of disease biomarkers. Rectal mucus is also of interest in the analysis of the gut flora. Whilst most studies use stool samples to study the luminal microbiome, there is an understanding that the mucosal microbiome is a distinct entity that may be more relevant.
Whilst the study will allow the feasibility and potential of a wide range of potential assays to be investigated, including those concentrating on the microbiome, the primary focus is on development of a screening test for colorectal cancer based on the detection of tumour-associated mutations and epigenetic markers. The planned study will use sequential cohorts of patient samples to underpin assay development and initial testing of assay performance. The initial phases of this study are exploratory in nature, looking at early development of clinical assays. The work then moves to more advanced phases of assay development, including validation, and aims to show proof-of-concept, confirming whether the OriCol™ Sampling Device can be used in the development of assays with potential clinical utility.Summary of Results
The Oricol-EGI-02 Study was granted ethical approval to commence in November 2019. Initially 8 subjects were recruited from a single site whilst other sites were in process of joining. However, from March 2020 all work ceased on this clinical trial due to the outbreak of the Covid-19 pandemic and move to national lockdown.The study was re-opened with four sites in late-2020 and recruitment continued to August 2022 when the last participant entered the study. The study had been extended to 800 participants (from original 600) and the study was formally closed in August 2023 when all participants had at least one year of follow-up. For those participants diagnosed with colorectal cancer, they are continuing to be monitored remotely annually.
The study was designed to use a novel device (the Oricol device) that is passed into the lower bowel (rectum) and the balloon inflated in the lower rectum with the balloon pressing against the inner lining of the bowel to collect a sample of mucus - the material that protects the cells making up the inner lining.
This rectal mucus is then retrieved and shipped by post to our laboratory, where the components of the mucus are separated to allow genomic analysis for fragments of cellular material (DNA) that have been shed from cancer cells (if present) further up the large bowel (colon).
Our initial publication (https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F36166177%2F&data=05%7C02%7Cnottingham1.rec%40hra.nhs.uk%7C8c620085250645cf19f608dcdbbeb457%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638626859326152960%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=EMUvfl7WNfFMF8yjVh%2BR1ojSHF%2B41Vsaesfb4ZPzI%2F8%3D&reserved=0) reported on the first 300 patients recruited to assess whether the use of the Oricol device was acceptable to patients as well as retrieving material for analysis. The internal pilot supported the underlying hypothesis being tested and demonstrated very high levels of patient acceptability, supporting continuation of the study. Data on all 800 patients further supports this demonstrating very high levels of patient acceptability (internal use only at present - publication to follow).
Having further refined and improved the sample handling processes and with separation of the sample into separate genomic parts, there has been ongoing analysis of the mutations that are detected between those with colorectal cancer and those without, analysis of patients with polyps as well as analysis of samples of patients with other conditions such as diverticular disease. Parallel analysis of the metholomic data, which represents which genes are being switched on or off in a process is ongoing and there is work to characterise the microbiome (gut bacteria) on each specimen to assess for relation to disease/symptoms.
This work is now coming to a close and uses mathematics called bioinformatics and biostatistics to assess for patterns that form signatures of a condition.
All of the participants that were recruited to the study were followed up for a minimum of one year to ensure that no bowel cancers were missed on the initial clinical assessment.
There were very few adverse events in the study, with no serious adverse events reported. The adverse events related to technical failures of the sample collection device (Oricol device) and this led to changes in the manufacturing process.
The results of this study will be released to the investigators from the four hospitals in December 2024 in a closed meeting. Following this and with their consent, publications will be submitted to peer reviewed scientific and clinical journals regarding the ability to detect bowel cancer, or exclude cancer from a single mucus sample taken from the lower bowel with no requirement to take bowel preparation.
The study was designed to test a new technology that would exclude bowel cancer in symptomatic patients and hence avoid the need for unnecessary invasive tests such as a colonoscopy, and with biobanking of samples and further testing allow recognition of other patterns of biological markers of conditions such as diverticulosis, inflammatory bowel disease, and functional bowel conditions often referred to as Irritable Bowel Syndrome (IBS).
On behalf of the investigators and the team at Origin Sciences we are extremely grateful to the participants for taking their time, when referred with symptoms leading to a concern for bowel cancer, to have taken part in this study.
REC name
East Midlands - Nottingham 1 Research Ethics Committee
REC reference
19/EM/0266
Date of REC Opinion
17 Sep 2019
REC opinion
Further Information Favourable Opinion