Division of Gastroenterology, Yokohama City University School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan.
BMC Cancer. 2012 Sep 19;12:413. doi: 10.1186/1471-2407-12-413.
Colorectal cancer (CRC) is one of the most commonly occurring neoplasms and a leading cause of cancer death worldwide, and new preventive strategies are needed to lower the burden of this disease. Eicosapentaenoic acid (EPA), the omega-3 polyunsaturated fatty acid that is widely used in the treatment of hyperlipidemia and prevention of cardiovascular disease, has recently been suggested to have a suppressive effect on tumorigenesis and cancer cell growth. In CRC chemoprevention trials, in general, the incidence of polyps or of the cancer itself is set as the study endpoint. Although the incidence rate of CRC would be the most reliable endpoint, use of this endpoint would be unsuitable for chemoprevention trials, because of the relatively low occurrence rate of CRC in the general population and the long-term observation period that it would necessitate. Moreover, there is an ethical problem in conducting long-term trials to determine whether a test drug might be effective or harmful. Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger in diameter and stain more darkly with methylene blue than normal crypts, are considered as a reliable surrogate biomarker of CRC. Thus, we devised a prospective randomized controlled trial as a preliminary study prior to a CRC chemoprevention trial to evaluate the chemopreventive effect of EPA against colorectal ACF formation and the safety of this drug, in patients scheduled for polypectomy.
This study is a multicenter, double-blind, placebo-controlled, randomized controlled trial to be conducted in patients with both colorectal ACF and colorectal polyps scheduled for polypectomy. Eligible patients shall be recruited for the study and the number of ACF in the rectum counted at the baseline colonoscopy. Then, the participants shall be allocated randomly to either one of two groups, the EPA group and the placebo group. Patients in the EPA group shall receive oral 900-mg EPA capsules thrice daily (total daily dose, 2.7 g per day), and those in the placebo group shall receive oral placebo capsules thrice daily. After one month's treatment with EPA/placebo, colonoscopic examination and polypectomy will be performed to evaluate the formation of ACF, and the cell-proliferative activity and cell-apoptotic activity in normal colorectal mucosa and colorectal polyps.
This is the first study proposed to explore the effect of EPA against colorectal ACF formation in humans.This trial has been registered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000008172.
结直肠癌（CRC）是最常见的肿瘤之一，也是全球癌症死亡的主要原因，因此需要新的预防策略来降低这种疾病的负担。二十碳五烯酸（EPA）是一种ω-3 多不饱和脂肪酸，广泛用于治疗高脂血症和预防心血管疾病，最近有研究表明其对肿瘤发生和癌细胞生长具有抑制作用。在 CRC 化学预防试验中，一般以息肉或癌症的发生率作为研究终点。尽管 CRC 的发生率是最可靠的终点，但由于普通人群中 CRC 的发生率相对较低，需要长期观察，因此使用该终点不适合化学预防试验。此外，进行长期试验以确定试验药物是否有效或有害存在伦理问题。异常隐窝病灶（ACF）定义为直径较大且用亚甲蓝染色比正常隐窝更深的隐窝病变，被认为是 CRC 的可靠替代生物标志物。因此，我们设计了一项前瞻性随机对照试验，作为 CRC 化学预防试验之前的初步研究，以评估 EPA 对结直肠 ACF 形成的化学预防作用和该药物在计划进行息肉切除术的患者中的安全性。
本研究是一项多中心、双盲、安慰剂对照、随机对照临床试验，在计划进行息肉切除术的结直肠 ACF 和结直肠息肉患者中进行。符合条件的患者将被招募入组，并在基线结肠镜检查时计算直肠内 ACF 的数量。然后，将参与者随机分配到 EPA 组和安慰剂组中的任意一组。EPA 组患者每日口服 900mg EPA 胶囊 3 次（每日总剂量为 2.7g），安慰剂组患者每日口服安慰剂胶囊 3 次。在 EPA/安慰剂治疗 1 个月后，进行结肠镜检查和息肉切除术，以评估 ACF 的形成情况，并评估正常结直肠黏膜和结直肠息肉中的细胞增殖活性和细胞凋亡活性。
这是第一项探索 EPA 对人类结直肠 ACF 形成影响的研究。该试验已在大学医院医疗信息网络（UMIN）临床试验注册中心注册，注册号为 UMIN000008172。
