Chemoprevention of Colorectal Cancer: the Role of Non-digestible Carbohydrates
试验速览
- 阶段
- 不适用
- 入组人数
- 75
- 试验地点
- 4
- 主要终点
- Faecal calprotectin concentration
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 85 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Attended for flexible sigmoidoscopy or colonoscopy and no macroscopic pathology identified
排除标准
- •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
结局指标
主要结局
Faecal calprotectin concentration
时间窗: 50 days
次要结局
- 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)