Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03663062 |
| Other study ID # |
OSCAR |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
December 27, 2017 |
| Est. completion date |
June 7, 2019 |
Study information
| Verified date |
September 2018 |
| Source |
South Tyneside and Sunderland NHS Foundation Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
In the UK, around 1 in 16 men and 1 in 20 women will develop bowel cancer at some point in
their lives. Most bowel cancers happen when a type of growth in the bowel called an adenoma
eventually becomes cancerous. Cutting out adenomas reduces the risk of developing bowel
cancer.
Certain people are more likely to have adenomas than others, for example people who are
overweight. People who are overweight are also more likely to develop liver disease by laying
too much fat down in the liver. Studies in Asia have shown that people with fatty liver
disease are more likely to have adenomas and these are more commonly found in the part of the
bowel (right colon) furthest from the bottom end.
Information on the link between obesity, fatty liver disease and adenomas is very limited,
particularly in the Western population.
The investigators will assess the link between body weight, fatty liver and adenomas in the
UK population. 1430 patients will be invited; some through the bowel cancer screening
programme and some with symptoms such as low blood count, bleeding or changed bowel habit.
These patients will already have been referred for a camera test looking into the bowel,
called a colonoscopy. Information including height, weight and some health questions will be
taken. Blood samples will be taken. The investigators will compare the number of patients
with adenomas who have liver disease or who are overweight with those who don't. This
information will be used to develop a scoring system to predict risk of adenomas. This will
help the investigators to decide if undertaking colonoscopies in these patients will identify
those at increased risk of bowel cancer.
Description:
Bowel cancer, or colorectal cancer (CRC), is the second most common cancer affecting both men
and women in England. The majority of CRCs develop from a pre-cancerous type of growth in the
bowel called an adenoma. Detecting and removing these adenomas is important in reducing CRC
risk. A study which undertook a once-off camera examination of the left hand side of the
bowel (flexible sigmoidoscopy), removing any adenomas, demonstrated a reduction in CRC by 23%
and reduced mortality by 31%.
Although a single cause for adenomas is not known, several factors can predispose patients to
adenomas, including; age, gender, family history, cigarette smoking and excess body weight
(EBW).
Obesity is becoming an increasing problem in the UK, with approximately a quarter of adults
classed as obese in England. Patients who are obese are at higher risk of having adenomas.
Studies have shown that patients with EBW are more likely to have fatty disease of the liver
(non-alcoholic fatty liver disease, NAFLD) by laying down fat in the liver. Studies in Asia
have shown that patients with NAFLD are more likely to have adenomas, and that these are more
likely to be in the right side of the bowel which is furthest from the anus (right colon).
Although these studies have shown a link between NAFLD and adenomas, they have all used
invasive or expensive markers of fatty liver disease. No study has correlated the link
between liver enzymes (blood tests) and adenomas or by using scoring systems to determine the
presence or absence of significant fatty liver disease. Furthermore, no Western studies have
confirmed the link between NAFLD and adenomas, meaning it is unclear whether this link is
only present in the Asian population.
Approximately 400,000 colonoscopies (camera examinations of the large bowel) are performed
each year within the NHS for the investigation of gastrointestinal symptoms, including:
altered bowel habit, rectal bleeding and low blood count. When polyps are found, patients
often have a follow-up surveillance colonoscopy to check that no new adenomas have formed.
The timing and need for surveillance is based only on the number and size of adenomas found
and does not take into account any risk factors which the patient may have.
The NHS Bowel Cancer Screening Programme (BCSP) invites all individuals aged 60-74 to
undertake a stool sample test which looks for blood, called faecal occult blood testing
(FOBt), every two years. Those who have a positive FOBt are then invited for a colonoscopy.
This programme is purely based on age and is not targeted. Another arm of the BCSP was
introduced in 2013, where all individuals aged 55 are invited for a flexible sigmoidoscopy
and removal of adenomas. Anyone who is felt to be high risk according to the number or size
of adenomas then undergoes a colonoscopy.
The BCSP has led to cancers being detected at an earlier stage, but is not protecting the
population against cancers in the right side of the bowel.
In summary, although studies in Asian populations have suggested an association between NAFLD
and colorectal adenomas, this has not been repeated in a Western population. It is important
that the association is explored further in a Western population, in a simple, non-invasive
manner. Assessing markers of NAFLD and a wider range of risk factors for adenomas will allow
us to develop a tool to predict which patients are at increased risk of adenomas, called a
risk model.
The OSCAR study is a multicentre observational study has been designed which will recruit
1430 participants from nine sites, eight in the North of England who are all members of the
Northern Region Endoscopy Group (NREG) and one from Kettering General Hospital NHS Trust.
NREG is an endoscopy research collaborative group with an excellent track record of
delivering similar endoscopy based research studies to time and target. Participation will
involve collecting information relating to obesity and fatty liver disease in patients
already attending for colonoscopy in addition to collecting information about the number and
size of any adenomas found.
All patients scheduled for colonoscopy will be provided with an invitation letter and patient
information sheet in addition with the standard information about the colonoscopy procedure
that the endoscopy unit provides. As colonoscopy requires a period of preparation prior to
the test, patients will receive this information at least 24 hours before the procedure,
allowing ample time to consider the study before attending the endoscopy department.
Taking part in this study will change very little about the patients' experience of the
colonoscopy test itself. If the patient agrees to take part in this study, the information
sheet will be reviewed with them by a research team member, an opportunity to ask questions
given, and the consent form signed. Eligibility to take part in the study will be checked,
and the patient will be weighed, have their height checked, waist circumference measured,
body mass index (BMI) calculated and blood pressure checked. A research team member will
undertake a health questionnaire which will include the following items:
1. Current and previous smoking history
2. Current and previous alcohol history
3. Current medications: including Aspirin, Statin, Insulin, non-steroidal anti-inflammatory
drugs (NSAIDs), Diabetic medication, antibiotics and others
4. Family history of colorectal cancer
5. Family history of ischaemic heart disease in a first degree relative under the age of 60
6. History of liver disease
7. History of hypertension
8. History of diabetes- Type I, Type II
9. History of chronic kidney disease (Stage 4/5)
10. History of atrial fibrillation
11. History of rheumatoid arthritis
12. Personal history of anti-obesity surgery
These will be entered onto the case report form (CRF).
An intravenous cannula (a thin, plastic tube which is inserted into a vein in the arm) is
then inserted as part of routine care before the colonoscopy procedure. Blood tests will be
taken from this at the time of insertion to prevent the need for a separate blood test. These
tests will include:
1. Bilirubin
2. Alanine aminotransferase (ALT)
3. Alkaline phosphatase (ALP)
4. Aspartate aminotransferase (AST)
5. Gamma-glutamyl transferase (GGT)
6. Full blood count (FBC)
7. HbA1c
8. Fasting blood glucose
9. Lipids: Cholesterol, HDL and Triglycerides
10. Albumin
11. Immunoglobulin A
Patients will also need to sign a separate consent form for the colonoscopy procedure itself
as part of routine practice.
The patient will then enter the procedure room as per usual practice for their colonoscopy.
During the procedure, the research team member will record data onto the CRF (procedural
data, findings at colonoscopy etc). The colonoscopy report will be generated as per the usual
practice in each unit.
A subset of patients will undergo Fibroscan, which is a non-invasive test to evaluate for
liver fibrosis, to explore the association between the presence of colorectal adenoma/CRC and
the presence of liver fibrosis.
After the procedure, the patient will enter the recovery ward and follow usual practice in
the unit. Although participants will remain in the study for 14 days to allow data collection
and to follow-up any abnormal results, participants will not require any further visits and
the majority will not be contacted by the research team. If a new abnormality is found on
checking blood samples, the patient will be contacted by a member of the research team and
advised to make an appointment with their General Practitioner (GP).
Statistical analysis will be undertaken by Professor Steven Rushton, Professor of Biological
Modelling at Newcastle University.
The primary outcome of this study is to develop a risk model which can be used to inform
colorectal neoplasia screening and surveillance guidelines and to inform a future study
targeting screening of higher risk individuals.
The secondary outcomes will support this model by identifying which demographics contribute
to increased predisposition to colorectal neoplasia, namely smoking history, alcohol intake,
and obesity (measured by BMI and waist circumference). The investigators also aim to assess
whether the presence or degree of liver fibrosis, as measured by FIB4 score and Fibroscan
affects the risk of colorectal neoplasia and by exploring the link between NAFLD, obesity and
colorectal neoplasia in terms of adenoma burden, site and histological features. Lastly, the
association between abnormal liver enzymes and colorectal neoplasia will be explored.
