Colorectal Chemoprevention with Calcium and Vitamin D

使用钙和维生素 D 进行结直肠化学预防

• 批准号: 8144874
• 负责人: John Anthony Baron
• 金额: $ 348.03万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-17 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8144874
• 关键词: Adverse event; Aftercare; Calcium; Calcium Carbonate; Caliber; Chemoprevention; Cholecalciferol; Clinical; Colonoscopy; Colorectal; Colorectal Adenoma; Colorectal Cancer; Creatinine; Data; Data Files; Double-Blind Method; Dysplasia; Effectiveness; Enrollment; Epidemiology; Event; Funding; Gastroenterologist; Genetic Polymorphism; Histology; Hospitalization; Imagery; Individual; Intestines; Kidney Calculi; Large Intestine; Lesion; Measures; Mucous Membrane; Neoplastic Polyp; Osteoporosis; Participant; Pathology; Patients; Phase; Placebos; Polyps; Prevention; Procedures; Qualifying; Questionnaires; Randomized; Reading; Receptor Gene; Recording of previous events; Recurrence; Risk; Safety; Schedule; Serum; Supplementation; Toxic effect; Villous; Vitamin D; Vitamin D3 Receptor; Woman; Work; adenoma; carcinogenesis; double-blind placebo controlled trial; follow-up; meetings; neoplastic; pre-clinical; prevent; randomized placebo controlled trial; treatment duration; treatment planning; tumor

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.

描述（由申请人提供）：此申请是针对CA098286的更新，这是一种多中心，双盲，随机，安慰剂对照试验，用于补充维生素D和/或钙，用于预防结直肠腺瘤。这项研究基于广泛的流行病学和实验数据，表明维生素D和钙在大肠中发挥抗可塑性作用。该研究涉及美国的11个临床中心，一个病理中心和一个协调中心。每个受试者在研究入学前的4个月中至少有一个大肠腺瘤，并完全结肠镜可视化结直肠粘膜，肠道中没有已知的息肉。排除研究剂毒性风险的受试者（例如，肾结石的近期历史）被排除在外，可能需要研究治疗的人（例如，骨质疏松症）。参与者同意避免将学习人员带到审判之外。合适的受试者以2 x 2阶乘方式随机分配给碳酸钙（1200毫克钙/天），维生素D（1000 IU/天），无论是药物还是安慰剂。根据每个受试者的胃肠病医生计划，我们为妇女提供选择的选择，或者在合格考试后的3年或5年后进行结肠镜的随访。结肠镜随访。作为安全措施，将在基线和治疗期间获得血清钙，肌酐和25-（OH）维生素D水平。该研究的主要终点是随访时肠道的一个或多个肿瘤息肉。评估晚期病变的影响将包括在次级分析中。在有关事件率和研究行为的保守假设下，我们将拥有超过89％的功率，以检测维生素D与安慰剂相对于安慰剂的腺瘤复发降低20％，以及85％的功率，可通过钙加上维生素D对单独的钙降低25％的降低。其他分析也将具有良好的统计能力。在资金的前5年中，入学人数几乎按时间表进行；我们将在2007年11月30日达到或超过目标入学率。迄今为止，受试者表现出非常符合研究程序和药物的符合性，并且由于不良事件（例如肾结石）或对研究药物的需求（例如骨质骨质造影），很少有受试者不得不停止随机治疗。现在，我们要求资金完成所有2,200名随机受试者的计划治疗和随访，为首次疗效分析做准备，并实施治疗后的随访。