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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01214681
• Other study ID #: 002
• Status: Active, not recruiting
• Phase: N/A
• First received: October 1, 2010
• Last updated: October 25, 2011
• Start date: May 2010
• Est. completion date: December 2012

Study information

• Verified date: October 2011
• Source: Newcastle University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: National Health ServiceUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 75
• Est. completion date: December 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 16 Years to 85 Years

Eligibility

Inclusion Criteria:

Attended for flexible sigmoidoscopy or colonoscopy and no macroscopic pathology identified

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Dietary Supplement:
• Maltodextrin and Amioca starch
12g Maltodextrin and 23g Amioca starch daily in divided doses for 50 days. Provided as a powder to be added to food or drink.
• Hi-maize 260
23g Hi-maize 260 and 12g Maltodextrin daily in divided doses for 50 days. Provided as a powder to be added to food or drink.
• Polydextrose
12g polydextrose and 23g amioca starch daily in divided doses for 50 days. Provided as a powder to be added to food or drink.
• Hi-maize 260 and polydextrose
12g polydextrose and 23g Hi-maize 260 daily in divided doses for 50 days. Provided as a powder to be added to food or drink.

Locations

Country	Name	City	State
United Kingdom	Wansbeck General Hospital	Ashington	Northumberland
United Kingdom	North Tyneside General Hospital	North Shields	Tyne & Wear

Sponsors (2)

Lead Sponsor	Collaborator
Newcastle University	Northumbria Healthcare NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (4)

Asp NG, van Amelsvoort JM, Hautvast JG. Nutritional implications of resistant starch. Nutr Res Rev. 1996 Jan;9(1):1-31. doi: 10.1079/NRR19960004. — View Citation

Auerbach MH, Craig SA, Howlett JF, Hayes KC. Caloric availability of polydextrose. Nutr Rev. 2007 Dec;65(12 Pt 1):544-9. Review. — View 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 — View Citation

Wächtershäuser A, Stein J. Rationale for the luminal provision of butyrate in intestinal diseases. Eur J Nutr. 2000 Aug;39(4):164-71. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Faecal calprotectin concentration		50 days	No
Secondary	Serum C reactive protein concentration		50 days	No
Secondary	COX 2 expression in mucosal biopsies		50 days	No
Secondary	Number and distribution of mitotic and apoptotic cells within colonic crypts (mucosal cell kinetics)		50 days	No
Secondary	Cellular CDK 4 RNA expression		50 days	No
Secondary	Cellular GADD45A RNA expression		50 days	No
Secondary	Target gene methylation (p16, GSTP1, RARß2, CDH1 GATA4 APC, SFRP1, 2, 4 and 5, AXIN2, DKK1 and WIF1)		50 days	No
Secondary	Global genetic methylation		50 days	No
Secondary	Cellular protein biomarker (CK8) expression		50 days	No
Secondary	Faecal pH		50 days	No
Secondary	Faecal bacterial abundance and population		50 days	No
Secondary	Faecal short chain fatty acid concentration		50 days	No
Secondary	Urinary short chain fatty acid concentration		50 days	No
Secondary	Plasma short chain fatty acid concentration		50 days	No