Chemoprevention of Colorectal Cancer: the Role of Non-digestible Carbohydrates
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|ClinicalTrials.gov Identifier: NCT01214681|
Recruitment Status : Unknown
Verified October 2011 by Newcastle University.
Recruitment status was: Active, not recruiting
First Posted : October 5, 2010
Last Update Posted : October 26, 2011
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.
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer||Dietary Supplement: Maltodextrin and Amioca starch Dietary Supplement: Hi-maize 260 Dietary Supplement: Polydextrose Dietary Supplement: Hi-maize 260 and polydextrose||Not Applicable|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||75 participants|
|Intervention Model:||Factorial Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Chemoprevention of Colorectal Cancer: the Role of Non-digestible Carbohydrates|
|Study Start Date :||May 2010|
|Estimated Primary Completion Date :||June 2012|
|Estimated Study Completion Date :||December 2012|
|Placebo Comparator: Placebo||
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.
|Experimental: Hi-maize 260||
Dietary Supplement: 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.
Dietary Supplement: 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||
Dietary Supplement: 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.
- Faecal calprotectin concentration [ Time Frame: 50 days ]
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01214681
|Wansbeck General Hospital|
|Ashington, Northumberland, United Kingdom, NE63 9JJ|
|North Tyneside General Hospital|
|North Shields, Tyne & Wear, United Kingdom, NE29 8NH|
|Study Director:||John Mathers, PhD||Newcastle University|
|Principal Investigator:||Naomi Willis, PhD||Newcastle University|