CALCIUM AND ASPIRIN PREVENTION TRIAL

说明(改编自调查员摘要)：修改 膳食补充剂和药物的致癌过程 是结肠癌预防研究中的一大重点。两个顺序 研究建议调查结合钙和钙的作用。 阿司匹林在结肠癌化学预防中的应用。两名特工 之所以选择是因为(A)广泛的流行病学和实验室数据 支持它们的化学预防潜力，(B)它们的安全概况 在他们的其他健康状况下被很好地描绘出来 惠益；(C)它们可能有补充的行动机制；和(D) 研究团队对这些代理人有相当丰富的经验。目标 人口将是有零星病史的研究对象 入院5年内无病史的结肠腺瘤性息肉 先前的恶性疾病。初步的2a阶段试验旨在 确定具有相关生物学特性的阿司匹林的最小剂量 活动。随后的随机、双盲、安慰剂对照 阶段2b试验旨在测试单一和组合 阿司匹林和钙的化学预防作用，给药12周。这个 阿司匹林剂量将在2a期试验中确定，钙 剂量将是先前证明的2000毫克/天的有效剂量。 主要终点是结肠粘膜前列腺素E_2水平和 用增殖细胞核抗原方法测定上皮细胞增殖指数。这个 研究人员推测，钙和阿司匹林会有一种 慢性阻塞性肺疾病患者结肠黏膜的协同、降低风险作用 腺瘤性息肉病史。这项研究将在 胃肠病专家网络，可以接触到大量的 腺瘤性息肉患者和丰富的化学预防经验 审判。2b阶段研究的数据将用于构建第三阶段 复发性息肉的研究。

DESCRIPTION (Adapted from the investigator's abstract): Modification of the carcinogenic process by dietary supplements and pharmacologic agents is a major emphasis in colon cancer prevention research. Two sequential studies are proposed to investigate the role of combined calcium and aspirin supplementation in colon cancer chemoprevention. The two agents are chosen because (a) extensive epidemiologic and laboratory data support their chemopreventive potential, (b) their safety profile has been well delineated in other health conditions in which they are of benefit, (c) they may have complementary mechanisms of action, and (d) the research team has considerable experience with these agents. Target populations will be subjects with a prior history of sporadic adenomatous polyps of the colon within 5 years of entry and no history of previous malignancy. A preliminary Phase 2a trial is designed to determine the minimum dose of aspirin which has relevant biologic activity. A subsequent randomized, double-blind, placebo controlled Phase 2b trial is designed to test the single and combined chemopreventive effects of aspirin and calcium, given for 12 weeks. The aspirin dose will be determined in the phase 2a trial, and the calcium dose will be the previously demonstrated effective dose of 2000 mg/d. The primary endpoints will be colonic mucosal prostaglandin E2 levels and epithelial proliferation indices measured by PCNA methodology. The investigators hypothesize that calcium and aspirin will have a synergistic, risk reducing effect on the colonic mucosa in subjects with a history of adenomatous polyps. The study will be performed in a network of gastroenterologists with access to a large population of adenomatous polyp patients and extensive experience in chemoprevention trials. Data from the phase 2b study will serve to construct a phase 3 study on recurrent polyps.