Colorectal Chemoprevention with Calcium and Vitamin D

描述（由申请人提供）：本申请是CA098286的续期，CA098286是一项多中心，双盲，随机，安慰剂对照试验，补充维生素D和/或钙以预防结直肠腺瘤。这项研究建立在广泛的流行病学和实验数据的基础上，表明维生素D和钙在大肠中都具有抗肿瘤作用。这项研究涉及美国的11个临床中心、一个病理中心和一个协调中心。每位受试者在研究开始前4个月内至少切除了一个大肠腺瘤，结肠镜检查显示结直肠粘膜完整，肠道内无已知息肉残留。有研究药物毒性风险的受试者（如近期有肾结石病史的受试者）和可能需要研究治疗的受试者（如骨质疏松症患者）均被排除在外。参与者同意避免在试验之外使用研究药物。合适的受试者以2 × 2因子的方式随机分为碳酸钙（1200mg钙/天）、维生素D （1000iu /天）、两种药物或安慰剂。我们让女性随机选择单独服用钙剂或服用钙剂加维生素d。结肠镜随访在资格考试后3年或5年进行，由每位受试者的胃肠病学家计划。作为安全措施，将在基线和治疗期间测定血清钙、肌酐和25-(OH)维生素D水平。研究的主要终点是随访中出现的一个或多个肠肿瘤息肉；对晚期病变的疗效评估将包括在二次分析中。在关于事件发生率和研究行为的保守假设下，我们将有超过89%的能力检测到维生素D与安慰剂相比腺瘤复发率降低20%，85%的能力检测到钙加维生素D与单独钙相比腺瘤复发率降低25%。其他分析也将具有良好的统计效力。在资助的前5年，入学几乎完全按照计划进行；我们将在2007年11月30日达到或超过我们的招生目标。到目前为止，受试者对研究程序和药物的依从性都很好，很少有受试者因为不良事件（如肾结石）或需要研究药物（如骨质疏松症）而不得不停止随机治疗。我们现在请求资金来完成所有2200名随机受试者的计划治疗和随访，准备第一次疗效分析，并实施治疗后随访。

DESCRIPTION (provided by applicant): This application is for the renewal of CA098286, a multicentered, double-blind, randomized, placebo controlled trial of supplementation with vitamin D and/or calcium for the prevention of colorectal adenomas. The study builds on extensive epidemiological and experimental data indicating that both vitamin D and calcium exert anti-neoplastic effects in the large bowel. The study involves 11 clinical centers in the US, a pathology center and a coordinating center. Each subject has at least one large bowel adenoma removed in the 4 months prior to study entry, with complete colonoscopic visualization of the colorectal mucosa and no known polyps remaining in the bowel. Subjects at risk for toxicity from study agents (e.g. with a recent history of kidney stones) are excluded, as are those with a likely need for the study treatments (e.g. with osteoporosis). Participants agree to avoid taking study agents outside the trial. Suitable subjects are randomized in a 2 x 2 factorial manner to calcium carbonate (1200 mg calcium/day), vitamin D (1000 IU/day), both agents, or placebo. We offer women the choice of being randomized to calcium alone or calcium plus vitamin D. Colonoscopic follow-up occurs at either 3 years or 5 years after the qualifying exam, as planned by each subject's gastroenterologist. As safety measures, serum calcium, creatinine and 25-(OH) vitamin D levels will be obtained at baseline, and during the treatment period. The main endpoint of the study is one or more neoplastic polyps of the bowel on followup; assessment of effects for advanced lesions will be included in secondary analyses. Under conservative assumptions regarding event rates and study conduct, we will have greater than 89% power to detect a 20% reduction in adenoma recurrence with vitamin D versus placebo, and 85% power to detect a 25% reduction in recurrence with calcium plus vitamin D versus calcium alone. Other analyses will also have good statistical power. During the first 5 years of funding, enrollment has proceeded almost exactly according to schedule; we will meet or exceed our target enrollment on November 30, 2007. To date, subjects have shown excellent compliance with study procedures and agents, and few subjects have had to stop randomized treatment because of adverse events (e.g. kidney stones) or a need for the study agents (e.g. osteoporosis). We now request funds to complete the planned treatment and follow-up for all 2,200 randomized subjects, prepare for the first efficacy analyses, and implement a post-treatment follow-up.