ASPIRIN/FOLATE PREVENTION OF LARGE BOWEL POLYPS

本申请是CA 59005“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、安慰剂对照析因设计临床试验，旨在评估阿司匹林和/或叶酸预防近期有大肠腺瘤病史的受试者复发大肠腺瘤的疗效。这项试验的动机是最近的流行病学和实验数据表明，叶酸和非甾体抗炎药，包括阿司匹林，在大肠中具有抗肿瘤特性。 由于肿瘤性息肉（腺瘤）是肠道的癌前病变，因此它们是这些效应试验的适当终点。这项研究始于1994年，当时只是对阿司匹林进行研究。 在1995年获得补充资金后，研究被转换为2 × 3析因设计，使用两种药物：叶酸（安慰剂或每日1 mg叶酸）和阿司匹林（安慰剂，80 mg或每日325 mg）。在研究入组时，受试者完成医学/个人史问卷以及食物频率问卷。 还在研究入组时采集血液样本，并储存作为DNA和血浆的来源，用于未来研究。 受试者最初入组3个月的阿司匹林导入期，在此期间评估研究的适用性，即阿司匹林耐受性和对研究程序的依从性。 随机化后每4个月，受试者填写一份关于研究药物依从性、药物和维生素/矿物质补充剂使用、疾病和住院情况的问卷。 计划在合格内镜检查后3年进行结肠镜随访和研究完成。受试者提供第二份血液样本和当时的食物频率问卷。1998年3月，招聘结束。 当时，共有1406例受试者入组试验：1028例接受随机化，268例被认为不适合随机化，110例仍处于3个月运行期。 到目前为止，受试者对研究的依从性非常好;根据自随机化以来的时间，83%-90%的受试者几乎服用了所有的研究片剂。有了这里所要求的资金，我们预计将完成治疗阶段和初步统计分析。 我们还建议在研究完成时测量尿血栓素B2、红细胞和血清叶酸。 这些将用作研究药物依从性的指标。

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.