ASPIRIN/FOLATE PREVENTION OF LARGE BOWEL POLYPS

这项申请是对CA59005“阿司匹林-叶酸预防肿瘤性息肉”的竞争性更新的重新提交，这是一项双盲、安慰剂对照因子设计临床试验，旨在研究阿司匹林和/或叶酸在近期有大肠腺瘤病史的受试者中预防大肠腺瘤复发的疗效。这项试验的动机是最近的流行病学和实验数据表明，叶酸和包括阿司匹林在内的非类固醇抗炎药在大肠中具有抗肿瘤特性。由于肿瘤性息肉(腺瘤)是肠道中的癌前病变，因此它们是试验这些影响的合适终点。这项研究始于1994年，当时只对阿司匹林进行了研究。在1995年获得补充资金后，这项研究转换为2×3析因设计，包括两种药物：叶酸(安慰剂或每天1毫克叶酸)和阿司匹林(安慰剂，每天80毫克或325毫克)。在研究进入时，受试者完成一份病史/个人史问卷以及一份食物频率问卷。在研究开始时，还会收集血液样本，作为DNA和血浆的来源储存起来，供未来研究使用。受试者最初参加为期3个月的阿司匹林磨合期，在此期间评估研究的适宜性，即对阿司匹林的耐受性和对研究程序的遵守。随机后每4个月，受试者完成一份关于研究药物依从性、药物和维生素/矿物质补充剂的使用、疾病和住院情况的问卷。结肠镜随访和研究完成计划在合格的内窥镜检查后3年内完成。受试者当时提供了第二次血样和食物频率调查问卷。1998年3月，招聘结束。当时，共有1406名受试者进入试验：1028名被随机分组，268名被认为不适合随机分组，110名仍处于3个月的运行期。到目前为止，受试者对研究的依从性一直很好；根据随机化以来的时间，83%-90%的受试者实际上正在服用他们所有的研究药片。有了这里要求的资金，我们预计完成治疗阶段和初步统计分析。我们还建议在研究完成时检测尿液中的血栓素B2、红细胞和血清叶酸。这些将被用作遵守研究代理的衡量标准。

This application is a resubmission for the competitive renewal of CA59005, "Aspirin-Folate Prevention of Neoplastic Polyps," a double-blind, placebo-controlled factorial design clinical trial of the efficacy of aspirin and/or folate in the prevention of the recurrence of large bowel adenomas in subjects with a recent history of these tumors. The trial was motivated by recent epidemiological and experimental data suggesting that folic acid and non-steroidal anti-inflammatory drugs, including aspirin, have anti-neoplastic properties in the large bowel. Since neoplastic polyps (adenomas) are pre-malignant lesions in the bowel, they are appropriate endpoints for trials of these effects. The study began in 1994 as an investigation of aspirin alone. After supplemental funding was secured in 1995, the investigation was converted to a 2 x 3 factorial design with two agents: folate (placebo or 1 mg folate daily), and aspirin (placebo, 80 mg, or 325 mg daily). At study entry, subjects complete a medical/personal history questionnaire as well as a food frequency questionnaire. A blood sample is also collected at study entry and stored as a source of DNA and plasma for future research. Subjects initially enroll in a 3-month aspirin run-in period during which suitability for the study is assessed, i.e. tolerance to aspirin and adherence to study procedures. Every 4 months after randomization, subjects complete a questionnaire regarding compliance with study agents, use of medications and vitamin/mineral supplements, illnesses, and hospitalizations. Colonoscopic follow-up and study completion is planned for 3 years after the qualifying endoscopy. Subjects provide a second blood sample and a food frequency questionnaire at that time. In March, 1998, recruitment ended. At that time, total of 1406 subjects had entered the trial: 1028 were randomized, 268 were considered unsuitable for randomization and 110 were still in the 3-month run-period. To date, compliance of subjects with the study has been excellent; depending on time since randomization, 83 percent-90 percent of subjects are taking virtually all their study tablets. With the funds requested here, we anticipate completion of the treatment phase and initial statistical analyses. We also propose to measure urinary thromboxane B2, and red blood cell and serum folate near the time of study completion. These will be used as measures of compliance with study agents.