Chemopreventive Effects of Mesalazine in Patients at High Risk of Recurrent (Nonfamilial) Colorectal Adenomas
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- UMC Utrecht
- 入组人数
- 74
- 试验地点
- 1
- 主要终点
- Apoptotic index
研究概览
简要总结
Several studies indicate that mesalazine might have a preventive effect on recurrence of adenomas in patients with and without inflammatory bowel disease. As mesalazine has limited adverse effects, it is an attractive candidate for chemoprevention. In this study we aim to investigate the antineoplastic properties of mesalazine in patients with sporadic colorectal adenomas.
详细描述
Rationale: Patients with sporadic colorectal adenomatous polyps removed by polypectomy have a high rate of polyp recurrence and carry an increased risk for the development of colorectal carcinoma (CRC). Chemoprevention may lower the rate of adenoma recurrence after polypectomy, thereby reducing the risk of development or death from CRC. Mesalazine is an attractive candidate for chemoprevention, since even during long-term use it has only limited systemic adverse effects and no gastrointestinal toxicity. In a prospective trial a trend towards reduced adenoma recurrence has been observed in high risk patients with a history of at least 3 sporadic colorectal adenomas treated with mesalazine. Identification of biologically relevant antineoplastic properties of mesalazine in patients with sporadic adenomatous polyps will support further investigation of mesalazine as chemopreventive agent against colorectal neoplasia in the sporadic setting. Growth inhibition of colonic epithelial cells through induction of apoptosis and inhibition of proliferation is widely recognized as a potential mechanism for chemoprevention of colorectal cancer. In vivo data suggest that mesalazine exerts pro-apoptotic and anti-proliferative effects on normal colorectal epithelial cells. Furthermore, there is in vitro evidence in CRC cells that mesalazine inhibits Wnt/beta-catenin signalling, an early and common inappropriately activated pathway in colorectal carcinogenesis and molecular target for chemoprevention.
Objective: Evaluate the effects of mesalazine therapy on histologically normal sigmoid and rectal mucosa in patients at high risk of recurrent sporadic colorectal adenomas.
Primary endpoints:
- change in apoptotic index after treatment as compared to placebo
- change in proliferation index and distribution of proliferating cells in crypts after treatment as compared to placebo
Secondary endpoint:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age: 50-75 years
- •having undergone complete colonoscopy with polypectomy for removal of
- •2 or more colorectal adenomas, irrespective of size, and/or
- •1 colorectal adenoma:
- •of at least 1 cm in diameter and/or
- •located proximal to the splenic flexure and/or
- •with high-grade dysplasia and/or villous histology
排除标准
- •inflammatory bowel disease
- •familial colorectal cancer syndrome
- •history of colorectal carcinoma
- •history of surgery to the large bowel (except appendectomy)
- •chronic renal insufficiency
- •chronic hepatic insufficiency
- •allergy to salicylates
- •diabetes mellitus (higher risk for developing renal disease)
- •coagulation disorder or anticoagulant use, which cannot be temporarily discontinued (precludes biopsy taking)
- •prescription use of acetylsalicylic acid or calcium carbasalate (high- and low-dose) or other NSAIDs
- •use of medicines which may interact with mesalazine: methotrexate, thiopurines, cyclosporine, coumarin anticoagulants and rifampicin
研究组 & 干预措施
Mesalazine
Mesalazine, 3 grams once daily for six months
干预措施: Mesalazine (Drug)
Placebo
Placebo, 3 grams, once daily for six months
干预措施: Placebo (Drug)
结局指标
主要结局
Apoptotic index
时间窗: 6 months
Change in apoptotic index after treatment with mesalazine as compared to placebo
Proliferation index
时间窗: 6 months
Change in proliferation index and distribution of proliferating cells in crypts after treatment with mesalazine as compared to placebo
次要结局
- Expression of β-catenin signaling pathway(6 months)
研究者
Prof. dr. P.D. Siersema
Prof. dr. (MD, PhD) P.D. Siersema
UMC Utrecht