Chemoprevention of Colorectal Cancer: the Role of Non-digestible Carbohydrates

Not Applicable

• Conditions: Colorectal Cancer
• Interventions: Dietary Supplement: Hi-maize 260; Dietary Supplement: Polydextrose; Dietary Supplement: Hi-maize 260 and polydextrose; Dietary Supplement: Maltodextrin and Amioca starch

• Registration Number: NCT01214681
• Lead Sponsor: Newcastle University

Brief Summary

Colorectal cancer is a common disease worldwide. 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.

Research into colorectal cancer is hampered by the fact that studies must take a very long time to produce results and be very large if the development of a cancer is the endpoint. Therefore alternative methods of quantifying the risk of developing a cancer are required so trials can be a realistic size and be completed in a realistic time frame. The investigators have previously identified several candidates for these 'biomarkers'. The next stage in proving or disproving these as useful biomarkers is to test their response to a dietary agent that the investigators know reduces the risk of colon cancer.

Detailed Description

This project is designed to enhance understanding of links between food and the health of the gut. The particular purpose of the project is to investigate the impact of a well-defined intervention in human volunteers on a panel of novel, and established, diet-related biomarkers of bowel cancer risk. We have developed a number of novel biomarkers of diet-related CRC risk measured in colo-rectal mucosal biopsies (and in stool). These biomarkers include differentially expressed proteins, DNA methylation markers and inflammation markers. In our on-going BORICC Study we are investigating the relationships between dietary exposure and nutritional status for these biomarkers in a cross-sectional study. The next logical step in this research is to determine whether a selected panel of the most promising biomarkers responds to a dietary intervention i.e. to test their utility as biomarkers of GI health and potential as surrogate endpoints in future human studies.

We propose to use Hi-maize 260 and polydextrose (PD) as our model resistant starch (RS) intervention agents. RS describes the fraction of dietary starch which is not digested in the small bowel and which flows to the colon where it is a substrate for bacterial fermentation. (Asp, 1996) PD is produced by the bulk melt polycondensation of glucose and sorbitol to produce an oligosaccharide with a mean degree of polymerisation of 12 which is resistant to mammalian GI enzymes and, like other RSs, is a substrate for bacterial fermentation. (Auerbach, 2007) Both Hi-maize and PD are fermented (to a greater or lesser extent) producing short-chain fatty acids (SCFA) including butyrate. (Asp, 1996) Butyrate has beneficial effects on gut physiology and immune function including anti-inflammatory effects. (Wächtershäuser, 2000; Dronamraju, 2009)

In the present project we will investigate the impact of PD and RS, as food-borne substrates for delivery of butyrate, on biomarkers of bowel cancer risk.

Study Timeline

• Study Start: 2010-05
• Study First Submitted: 2010-10-01
• Study First Submitted QC: 2010-10-04
• Study First Posted: 2010-10-05
• Status Verified: 2011-10
• Last Update Submitted: 2011-10-25
• Last Update Posted: 2011-10-26
• Primary Completion: 2012-06
• Study Completion: 2012-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

Attended for flexible sigmoidoscopy or colonoscopy and no macroscopic pathology identified

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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 NSAID
• Other immunosuppressive medication
• Active colonic inflammation at endoscopy
• Incomplete left sided examination
• Colorectal carcinoma found at endoscopy
• Iatrogenic perforation at endoscopy
• Colorectal cancer on histology
• Warfarin or other anticoagulant use
• Diabetes mellitus
• Crohn's disease
• Cognitive impairment

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Hi-maize 260	Hi-maize 260	-
Polydextrose	Polydextrose	-
Hi-maize 260 and polydextrose	Hi-maize 260 and polydextrose	-
Placebo	Maltodextrin and Amioca starch	-

Primary Outcome Measures

Name	Time	Method
Faecal calprotectin concentration	50 days

Secondary Outcome Measures

Name	Time	Method
Global genetic methylation	50 days
Cellular protein biomarker (CK8) expression	50 days
Faecal pH	50 days
Serum C reactive protein concentration	50 days
COX 2 expression in mucosal biopsies	50 days
Number and distribution of mitotic and apoptotic cells within colonic crypts (mucosal cell kinetics)	50 days
Cellular CDK 4 RNA expression	50 days
Cellular GADD45A RNA expression	50 days
Target gene methylation (p16, GSTP1, RARβ2, CDH1 GATA4 APC, SFRP1, 2, 4 and 5, AXIN2, DKK1 and WIF1)	50 days
Faecal bacterial abundance and population	50 days
Faecal short chain fatty acid concentration	50 days
Urinary short chain fatty acid concentration	50 days
Plasma short chain fatty acid concentration	50 days

Trial Locations

Locations (2)

North Tyneside General Hospital; 🇬🇧 North Shields, Tyne & Wear, United Kingdom

Wansbeck General Hospital; 🇬🇧 Ashington, Northumberland, United Kingdom