RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF MERIVA (R) AS A CANDIDATE CHEMOPREVENTION AGENT FOR GASTRIC CARCINOGENESIS

MERIVA (R) 作为胃癌候选化学预防药物的随机、双盲、安慰剂对照试验

• 批准号: 9931089
• 负责人: PAUL LIMBURG
• 金额: $ 2.68万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2022-02-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9931089
• 关键词: Africa; American Cancer Society; Antioxidants; Arachidonic Acids; Asia; Asians; Atrophic Gastritis; Bioflavonoid; Biological; CXCL10 gene; Cancer Burden; Cancer Etiology; Central America; Cessation of life; Chemoprevention; Chemopreventive Agent; Country; Curcumin; DNA Damage; Developing Countries; Diagnosis; Diet; Disease; Eastern Europe; Encapsulated; Europe; Far East; Flow Cytometry; Formulation; Gastric mucosa; Genotype; Histology; Human; IL8 gene; Incidence; Indium-111; Individual; Interleukin-1 beta; Intestinal Metaplasia; Intestinal Mucosa; Investigation; Japan; Lecithin; Legal patent; Liposomes; Lipoxygenase; Malignant Neoplasms; Metabolism; Methods; Molecular; Multifocal Lesion; North America; Outcome; Participant; Pathway interactions; Persons; Phenols; Placebos; Plants; Populations at Risk; Premalignant; Prostaglandin-Endoperoxide Synthase; Randomized; Reporting; Research Personnel; Resources; Rhizome; Risk; Safety; South America; Southern Europe; Stomach; Survival Rate; TNF gene; Technology; Tumeric; Woman; absorption; cancer type; carcinogenesis; chemokine; cytokine; disability-adjusted life years; double-blind placebo controlled trial; immunoregulation; inflammatory marker; inhibitor/antagonist; magnetic beads; malignant stomach neoplasm; men; mortality; off-patent; primary endpoint; routine screening; secondary endpoint; soy; years of life lost

Gastric cancer (GC) is the 4th most common incident cancer and the 2nd leading cause of cancer death worldwide.1 Approximately 990,000 people are diagnosed with GC worldwide, of whom close to 75% die from this disease.2 GC also is responsible for one of the highest cancer burdens, as determined by disability-adjusted life years lost.3 Despite the overall decrease in the incidence of GC since the 1930s, the annual global burden of cancer is projected to double by 2030 to 22.2 million incident cases and 13.1 million deaths, with over two-thirds of the burden in resource-limited nations.4, 5 In the US, the American Cancer Society estimates that in 2015 24,590 new cases of GC will be diagnosed and approximately 10,720 individuals will die from this type of cancer.6 The average risk that a person will develop GC in his/her lifetime is about 1 in 111, with the risk being 2 to 3-fold higher in men than women. However, GC incidence rates vary dramatically across different countries and are higher in less developed countries.2 GC is more common in East Asia, Southern and Eastern Europe, and South and Central America whereas the lowest incidence rates are observed in Africa and North America.7 Although nearly 60% of the new GC cases are diagnosed in Asia,8 significantly better outcomes have been reported among Asian individuals compared to those diagnosed in Western countries.9 Five-year GC survival rates are 40% lower in the US and Europe compared to Japan.10 With the high GC mortality-to-incidence ratio and the lack of routine screening methods available for asymptomatic individuals, the management of GC remains a challenge and warrants further investigations to more fully understand the biologic basis of progression and to develop chemopreventive strategies for individuals at increased risk. Curcumin is a phenolic antioxidant compound derived from the rhizome of the plant Curcuma longa. This bioflavonoid is a potent inhibitor of arachidonic acid metabolism, and blocks both lipoxygenase and cyclooxygenase activity in the intestinal mucosa. Curcumin exerts a variety of additional immunomodulatory and antioxidant effects and is thought to have broad chemopreventive potential through a variety of molecular mechanisms and cellular pathways, as recently reviewed.11 The investigators (Drs. Cruz-Correa & Morgan) from the Mayo Consortium are proposing a chemopreventive trial on a population at risk for gastric cancer (GC) using Meriva (a liposome-encapsulated formulation of curcumin) and placebo. The hypothesis is that curcumin given to individuals with gastric precancerous lesions – multifocal atrophic gastritis (MAG) & intestinal metaplasia (IM) will have a decrease in markers of inflammation including DNA damage, as compared to placebo, after six months of taking the study agent. Meriva® (Curcumin) is a patented formula of curcumin that includes a dietary phenolic with soy lecithin (non-GMO). The curcumin content and the curcuminoid absorption is 27 fold higher when compared to curcumin alone.

胃癌（GC）是全球第四大最常见的癌症事件和第二大癌症死亡原因。1全球约有990，000人被诊断患有GC，其中近75%死于这种疾病。2 GC也是最高癌症负担之一，尽管自20世纪30年代以来GC的发病率总体下降，预计到2030年，全球每年的癌症负担将翻一番，达到2220万例发病病例和1310万例死亡，其中超过三分之二的负担发生在资源有限的国家。4，5在美国，美国癌症协会估计，2015年，将有590例新的胃癌病例被诊断出来，大约10，720人将死于这种类型的癌症。6一个人一生中患胃癌的平均风险约为1/111，男性的风险比女性高2至3倍。然而，不同国家的GC发病率差异很大，欠发达国家的发病率更高。2 GC在东亚、南欧和东欧以及南美洲和中美洲更常见，而非洲和北美洲的发病率最低。7尽管近60%的新发GC病例在亚洲诊断，8据报道，与西方国家诊断的患者相比，亚洲患者的预后明显更好。9美国和欧洲的5年GC生存率比日本低40%。10 由于胃癌的发病率与死亡率之比很高，且无症状个体缺乏常规筛查方法，胃癌的管理仍然是一个挑战，需要进一步研究，以更充分地了解进展的生物学基础，并为风险增加的个体制定化学预防策略。 姜黄素是一种酚类抗氧化剂化合物，来源于植物姜黄的根茎。该双羟萘酸是花生四烯酸代谢的有效抑制剂，并阻断肠粘膜中的脂氧合酶和环氧合酶活性。姜黄素发挥各种额外的免疫调节和抗氧化作用，并被认为具有广泛的化学预防潜力，通过各种分子机制和细胞途径，如最近审查。 来自马约联盟的研究人员（Cruz-Correa和Morgan博士）正在提议使用Meriva（姜黄素的脂质体胶囊制剂）和安慰剂对胃癌（GC）风险人群进行化学预防试验。假设是，服用研究药物六个月后，与安慰剂相比，给予患有胃癌前病变-多灶性萎缩性胃炎（MAG）和肠上皮化生（IM）的个体的姜黄素将减少炎症标志物，包括DNA损伤。 Meriva®（姜黄素）是一种姜黄素的专利配方，其中包括大豆卵磷脂（非转基因）的膳食酚。姜黄素含量和类姜黄素吸收是单独姜黄素的27倍。