Eicosapentaenoic acid (EPA) efficacy for colorectal aberrant crypt foci (ACF): a double-blind randomized controlled trial.
Eicosapentaenoic acid (EPA) efficacy for colorectal aberrant crypt foci (ACF): a double-blind randomized controlled trial.
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DOI：
10.1186/1471-2407-12-413
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发表时间：
2012-09-19
期刊：
影响因子：
3.8
通讯作者：
Nakajima A
中科院分区：
文献类型：
--
作者：
Higurashi T;Hosono K;Endo H;Takahashi H;Iida H;Uchiyama T;Ezuka A;Uchiyama S;Yamada E;Ohkubo H;Sakai E;Maeda S;Morita S;Natsumeda Y;Nagase H;Nakajima A
结直肠癌（CRC）是世界范围内最常见的肿瘤之一，也是癌症死亡的主要原因，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）是广泛用于治疗高脂血症和预防心血管疾病的ω-3多不饱和脂肪酸，最近被认为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，通常将息肉或癌症本身的发生率设定为研究终点。尽管CRC的发生率是最可靠的终点，但由于CRC在一般人群中的发生率相对较低且需要长期观察期，因此使用该终点不适合化学预防试验。此外，在进行长期试验以确定试验药物是否有效或有害时存在伦理问题。异常隐窝病灶（ACF）是指病变中含有直径较大的隐窝，且亚甲基蓝染色较深，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对结肠直肠ACF形成的化学预防作用以及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、随机对照试验，在计划行息肉切除术的结直肠ACF和结直肠息肉患者中进行。应招募合格患者参加研究，并在基线结肠镜检查时计数直肠中的ACF数量。然后，参与者将被随机分配到两组之一，EPA组和安慰剂组。EPA组患者应每日三次口服900 mg EPA胶囊（每日总剂量为2.7 g），安慰剂组患者应每日三次口服安慰剂胶囊。在用EPA/安慰剂治疗一个月后，将进行结肠镜检查和息肉切除术以评价ACF的形成以及正常结直肠粘膜和结直肠息肉中的细胞增殖活性和细胞凋亡活性。这是第一项研究提出探索EPA对人类结直肠ACF形成的影响。该试验已在大学医院医学信息网络（UMIN）临床试验注册处注册为UMIN 000008172。
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.
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