Overview

This trial is active, not recruiting.

Condition colorectal cancer
Treatments maltodextrin and amioca starch, hi-maize 260, polydextrose, hi-maize 260 and polydextrose
Sponsor Newcastle University
Collaborator Northumbria Healthcare NHS Foundation Trust
Start date May 2010
End date June 2012
Trial size 75 participants
Trial identifier NCT01214681, 002

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model factorial assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose prevention
Arm
(Placebo Comparator)
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.
(Experimental)
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.
(Experimental)
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.
(Active Comparator)
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.

Primary Outcomes

Measure
Faecal calprotectin concentration
time frame: 50 days

Secondary Outcomes

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

Eligibility Criteria

Male or female participants from 16 years up to 85 years old.

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

Additional Information

Official title Chemoprevention of Colorectal Cancer: the Role of Non-digestible Carbohydrates
Principal investigator Naomi Willis, PhD
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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2011.
Information provided to ClinicalTrials.gov by Newcastle University.