Biomarkers Of Colorectal cancer After Bariatric Surgery

ISRCTN	ISRCTN95459522
DOI	https://doi.org/10.1186/ISRCTN95459522
Secondary identifying numbers	N/A

Submission date: 14/11/2013
Registration date: 19/12/2013
Last edited: 16/05/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Colorectal (bowel) cancer is a common disease. Obesity is a major health problem and is a known risk factor for bowel cancer. Weight loss surgery is increasingly being used in the management of severe obesity. However, the effect of weight loss surgery on bowel cancer risk is not known. In our previous work we have developed a number of unique biomarkers of bowel cancer risk, which can be measured in small samples (biopsies) taken from the bowel during an examination of the bowel (rigid igmoidoscopy). We have shown that these biomarkers can be detected before the development of bowel cancer and so may be a useful tool to identify those at higher risk of the disease. This study will tell us if obesity and surgically induced weight loss can affect these biomarkers and as a result influence the risk of developing bowel cancer in the future.

Who can participate?
This study aims to recruit about 40 adult men and women who are planned for weight loss surgery. We also aim to recruit 20 healthy volunteers who are not overweight or obese.

What does the study involve?
Blood, urine and stool samples and bowel wall biopsies, as well as body measurements and data on dietary, lifestyle and bowel habits, will be collected from a group of obese patients before and six months after weight loss surgery. We will collect similar samples and data from healthy normal weight individuals to use as a comparison. We can then look for any changes in the expression of these biomarkers, as well as a number of other important cancer-related measures.

What are the possible benefits and risks of participating?
There will be no immediate direct benefit to those taking part. There is a very small risk of causing bleeding and an even smaller risk of causing a perforation (hole or tear) when taking biopsies from the bowel. Steps are taken to minimise these risks.

Where is the study run from?
North Tyneside General Hospital (UK)

When is study starting and how long is it expected to run for?
Participants will be enrolled on the study for a minimum period of one year starting from November 2013; however, the enrolment period may be extended if necessary. The study is expected to run until the end of April 2016.

Who is funding the study?
Northumbria Healthcare Foundation Trust (UK)

Who is the main contact?
Dr Sorena Afshar
sorena.afshar@ncl.ac.uk

Contact information

Prof John Mathers
Scientific

Newcastle University
Biomedical Research Building
Campus for Ageing and Vitality
Newcastle-upon-Tyne
NE4 5PL
United Kingdom

Phone	+44 (0)191 2481133
Email	john.mathers@newcastle.ac.uk

Dr Sorena Afshar
Scientific

Human Nutrition Research Centre
Institute of Cellular Medicine
Newcastle University
Campus for Ageing and Vitality
Newcastle upon Tyne
NE4 5PL
United Kingdom

ORCID ID	0000-0002-4676-8117
Phone	+44 (0)191 208 1141
Email	sorena.afshar@ncl.ac.uk

Study information

Study design	Single-centre observational study
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Diagnostic
Participant information sheet	Patient information can be found at: http://www.ncl.ac.uk/hnrc/opportunities/documents/Informationsheetv2.1.pdf
Scientific title	Impact of obesity surgery on biomarkers of risk of colorectal cancer
Study acronym	BOCABS
Study objectives	1. What is the impact of weight loss surgery on biomarkers of colorectal cancer risk? 2. What is the difference, in terms of the impact on the expression of biomarkers of colorectal cancer risk, between the most commonly performed types of weight loss procedures (gastric bypass, sleeve gastrectomy, gastric balloon and gastric band)? 3. What factors, other than weight loss after the weight loss procedures, impact on the biomarkers of CRC risk (such as the effects on insulin pathways, inflammatory pathways and the gut luminal content)?
Ethics approval(s)	NRES Committee North East - Newcastle & North Tyneside 2, 02/08/2013, ref: 13/NE/0204
Health condition(s) or problem(s) studied	Obesity; Colorectal cancer; Bariatric surgery
Intervention	BOCABS is an observational study of patients undergoing weight loss surgery. Pre-operatively participants will have anthropometric measurements. A food portion size estimation interview will be carried out using a photographic food atlas. The participants will be asked to complete a validated food frequency questionnaire, lifestyle questionnaire and a Bristol stool chart diary. Fasting bloods and urine and stool samples will be collected. Rectal biopsies will be obtained using rigid sigmoidoscopy. The participants will be asked to wear an accelerometer (GeneActiv wrist worn physical activity monitor) during awake hours for one week. At the preoperative upper GI endoscopy, as part of routine care, duodenal biopsies will be taken for research purposes. Body composition analysis will be performed using a bioimpedance device (Tanita TBF300MA). Similar measurements and samples will be taken at the 6-month post-operative follow-up (apart from visceral fat and duodenal biopsies). This will also be the case for the 'normal weight' healthy control group. Participation will be over a six-month period.
Intervention type	Procedure/Surgery
Primary outcome measure	Epithelial cell kinetics of rectal mucosa measured using direct counting of mitotic figures after crypt microdissection; at baseline and repeated at 6 months for those who have bariatric surgery.
Secondary outcome measures	1. Epigenetic markers (Wnt signalling pathway) measured using pyrosequencing 2. Gene expression (Wnt signalling pathway) measured using qPCR 3. Mucosal expression of inflammatory markers measured using qPCR and/or immunohistochemistry All secondary outcomes will be measured at baseline for all participants and repeated at 6 months for those who have bariatric surgery.
Overall study start date	11/11/2013
Completion date	30/04/2016

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	60
Key inclusion criteria	Current inclusion criteria as of 11/12/2014: Intervention group: Obese adult patients planned for bariatric surgery Control group: Healthy adult patients with a normal Body Mass Index (18.5 to 24.9 kg/m2) and a recent (within 1 year) normal endoscopic (colonoscopy or flexible sigmoidoscopy) examination. Previous inclusion criteria: Intervention group: Obese adult patients planned for bariatric surgery Control group: Healthy adult patients with a normal Body Mass Index (18.5 to 24.9 kg/m2) and either: 1. A recent (within 6 months) normal colonoscopy undergoing minor anorectal surgery 2. The need for a rigid sigmoidoscopy & completion colonoscopy, as part of routine care
Key exclusion criteria	Pre-bariatric surgery/controls: 1. Age under 16 years old or over 65 years old 2. Previous colorectal resection 3. Previous weight loss surgery 4. Active or previous history of any type of Inflammatory Bowel Disease 5. Familial adenomatous polyposis 6. Lynch syndrome (Amsterdam II criteria) 7. Steroids, except topical, or other immunosuppressive medication 8. Warfarin or other anticoagulation Added 11/12/2014: 9. Pregnancy Post-bariatric surgery: 1. Major post-operative complications (defined using Clavien-Dindo classification ≥3) 2. Pregnancy Exclusion based on rigid sigmoidoscopy findings: 1. Difficulty in performing rigid sigmoidoscopy, either due to anal pathology or other technical difficulty 2. Macroscopically abnormal rectal mucosa 3. Unexpected microscopic abnormality on histological examination of rectal biopsies (e.g. microscopic colitis) Removed as of 11/12/2014: Additional exclusion for the 'normal weight' healthy controls: 1. Significant pathology on follow-up colonoscopy
Date of first enrolment	11/11/2013
Date of final enrolment	30/04/2015

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

North Tyneside General Hospital

Northumbria Healthcare Foundation Trust
Rake Lane
North Shields
NE29 8NH
United Kingdom

Sponsor information

Northumbria Healthcare NHS Foundation Trust (UK)
Hospital/treatment centre

North Tyneside General Hospital
Rake Lane
North Shields
NE29 8NH
England
United Kingdom

Phone	+44 (0)844 811 8111 (ext 2842 or 2816)
Email	caroline.potts@nhct.nhs.uk
Website	https://www.northumbria.nhs.uk
"ROR"	https://ror.org/01gfeyd95

Funders

Funder type

Hospital/treatment centre

Northumbria Healthcare Foundation Trust (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
Publication and dissemination plan	To be confirmed at a later date
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/04/2018		Yes	No
HRA research summary			28/06/2023	No	No

Editorial Notes

16/05/2018: Publication reference added.

11/12/2014: The following changes were made to the trial record:
1. The overall trial end date was changed from 31/03/2016 to 30/04/2016.
2. The target number of participants was changed from 95 to 60.