Clinical trial NCT01075893: Changes in Stem Cells of the Colon in Response to Increased Risk of Colorectal Cancer
Official title: Changes in Stem Cells of the Colon in Response to Increased Risk of Colorectal Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colorectal Cancer
Keywords: Colorectal cancer
Stem cells
Ulcerative colitis
Polyps
Lead sponsor: Newcastle University
Sponsor class: OTHER
Collaborators: name: Northumbria Healthcare NHS Foundation Trust
First posted: 2010-02-25
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients referred for lower gastrointestinal (GI) endoscopy at a participating centre will be considered for inclusion. Patients with a previous adenomatous polyp resection under surveillance will be considered for inclusion to the polyp group. Patients with ulcerative colitis under surveillance will be considered for inclusion to the ulcerative colitis group.

Brief summary: Colorectal cancer is a common disease worldwide. Increasing evidence is demonstrating that colorectal cancers arise from 'cancer stem cells.' Stem cells in the colon reside at the bottom of thousands of microscopic crypts throughout the wall of the colon. They create all the cells lining the bowel wall. These cells are created in the base of the crypt and ascend to the top acquiring the characteristics of mature cells of the bowel wall as they ascend.

It is now thought that colorectal cancer cells arise from stem cells where the genetic material regulating growth and division of the stem cell has become defective. This leads to unregulated production of cells which in turn have defective genetic information and cancer formation.

Prior studies have demonstrated that the earliest changes before a cancer develops are changes in cellular proliferation. Now that reliable markers to identify stem cells have been found, the researchers aim to investigate stem cell numbers and changes in distribution in those at normal risk of colorectal cancer and those at higher risk. The researchers hypothesise that changes in cellular proliferation at the top of the crypt in individuals at higher risk of colorectal cancer are due to a change in the number of stem cells in the crypt base.


Eligibility criteria: Inclusion Criteria:

* Referred for endoscopy at participating centre

Exclusion Criteria:

* Age \<16 or \>85
* Familial polyposis syndrome
* Lynch syndrome
* Known colorectal tumour
* Previous colorectal resection
* Pregnancy
* Chemotherapy in last 6 months
* Therapy with aspirin/other nonsteroidal anti-inflammatory drug (NSAID)
* Other immunosuppressive medication
* Incomplete left sided examination
* Colorectal carcinoma found at endoscopy
* Iatrogenic perforation at endoscopy
* Colorectal cancer on histology
* Microscopic colitis on histology

For the colitis group

* Simple clinical colitis activity index (SCCAI) score \> 5

Primary outcomes:
measure: Number of stem cells in the colonic crypt
timeFrame: On day of endoscopy
Secondary outcomes:
measure: Stem cell position in colonic crypt
timeFrame: On day of endoscopy
Other outcomes:
Locations:
city: Ashington
country: United Kingdom
facility: Wansbeck General Hospital
state: Tyne & Wear
city: North Shields
country: United Kingdom
facility: North Tyneside Hospital
state: Tyne & Wear
Study officials:
affiliation: Newcastle University, UK
name: Iain JD McCallum, MBChB MRCS
role: PRINCIPAL_INVESTIGATOR
affiliation: Newcastle University, UK
name: John C Mathers, PhD
role: STUDY_CHAIR
affiliation: Newcastle University, UK
name: Seamus B Kelly, MD FRCS
role: STUDY_DIRECTOR
affiliation: Northumbria NHS foundation trust
name: Mike Bradburn, MD FRCS
role: STUDY_DIRECTOR
References:
citation: Dronamraju SS, Coxhead JM, Kelly SB, Burn J, Mathers JC. Cell kinetics and gene expression changes in colorectal cancer patients given resistant starch: a randomised controlled trial. Gut. 2009 Mar;58(3):413-20. doi: 10.1136/gut.2008.162933. Epub 2008 Oct 31.
citation: Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007 Oct 25;449(7165):1003-7. doi: 10.1038/nature06196. Epub 2007 Oct 14.