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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2011 by Newcastle University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Northumbria Healthcare NHS Foundation Trust
Information provided by (Responsible Party):
Newcastle University
ClinicalTrials.gov Identifier:
NCT01214681
First received: October 1, 2010
Last updated: October 25, 2011
Last verified: October 2011
  Purpose

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 Intervention
Colorectal Cancer
Dietary Supplement: Maltodextrin and Amioca starch
Dietary Supplement: Hi-maize 260
Dietary Supplement: Polydextrose
Dietary Supplement: Hi-maize 260 and polydextrose

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Chemoprevention of Colorectal Cancer: the Role of Non-digestible Carbohydrates

Resource links provided by NLM:


Further study details as provided by Newcastle University:

Primary Outcome Measures:
  • Faecal calprotectin concentration [ Time Frame: 50 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Serum C reactive protein concentration [ Time Frame: 50 days ] [ Designated as safety issue: No ]
  • COX 2 expression in mucosal biopsies [ Time Frame: 50 days ] [ Designated as safety issue: No ]
  • Number and distribution of mitotic and apoptotic cells within colonic crypts (mucosal cell kinetics) [ Time Frame: 50 days ] [ Designated as safety issue: No ]
  • Cellular CDK 4 RNA expression [ Time Frame: 50 days ] [ Designated as safety issue: No ]
  • Cellular GADD45A RNA expression [ Time Frame: 50 days ] [ Designated as safety issue: No ]
  • Target gene methylation (p16, GSTP1, RARβ2, CDH1 GATA4 APC, SFRP1, 2, 4 and 5, AXIN2, DKK1 and WIF1) [ Time Frame: 50 days ] [ Designated as safety issue: No ]
  • Global genetic methylation [ Time Frame: 50 days ] [ Designated as safety issue: No ]
  • Cellular protein biomarker (CK8) expression [ Time Frame: 50 days ] [ Designated as safety issue: No ]
  • Faecal pH [ Time Frame: 50 days ] [ Designated as safety issue: No ]
  • Faecal bacterial abundance and population [ Time Frame: 50 days ] [ Designated as safety issue: No ]
  • Faecal short chain fatty acid concentration [ Time Frame: 50 days ] [ Designated as safety issue: No ]
  • Urinary short chain fatty acid concentration [ Time Frame: 50 days ] [ Designated as safety issue: No ]
  • Plasma short chain fatty acid concentration [ Time Frame: 50 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 75
Study Start Date: May 2010
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Experimental: Polydextrose 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.

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.

  Eligibility

Ages Eligible for Study:   16 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01214681

Locations
United Kingdom
Wansbeck General Hospital
Ashington, Northumberland, United Kingdom, NE63 9JJ
North Tyneside General Hospital
North Shields, Tyne & Wear, United Kingdom, NE29 8NH
Sponsors and Collaborators
Newcastle University
Northumbria Healthcare NHS Foundation Trust
Investigators
Study Director: John Mathers, PhD Newcastle University
Principal Investigator: Naomi Willis, PhD Newcastle University
  More Information

Publications:
Responsible Party: Newcastle University
ClinicalTrials.gov Identifier: NCT01214681     History of Changes
Other Study ID Numbers: 002
Study First Received: October 1, 2010
Last Updated: October 25, 2011
Health Authority: United Kingdom: National Health Service
United Kingdom: Research Ethics Committee

Keywords provided by Newcastle University:
Biomarkers
Colorectal cancer
Resistant starch
Polydextrose
Non-digestible carbohydrate

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on September 18, 2014