Contract HHSN261201200035I, Cancer Prevention Agent Development Program: Early Phase Clinical Research, 9/24/2012 - 9/23/2017Task Order HHSN26100005, Phase I Trial of Berberine in Subjects with U

西安西京医院的研究人员中国提出了一项I期双盲、安慰剂对照、随机试验，黄连素用于临床缓解的溃疡性结肠炎(UC)患者，美沙拉明用于维持治疗。UC患者患结肠炎相关性癌症(CAC)的风险增加，CAC是结直肠癌的一种。鉴于这种增加的风险，建议每年进行多次活检的结肠镜检查。UC缓解期患者通常会开美沙拉明，这通常有助于控制症状，但没有报道对癌症发病率有影响。在过去的50年里，UC在世界各地的发病率和患病率一直在上升，这表明它已经成为一种全球性疾病。 黄连素是一种从植物中提取的物质，在美国可作为膳食补充剂使用，已被中国食品药品监督管理局批准为非处方药，广泛用于治疗胃肠炎和腹泻。黄连素在几个临床试验中显示了抗菌、抗氧化和抗炎活性，并在临床前模型中显示了抗癌活性。虽然这种化合物有广泛的安全性数据，这是医生经常给中国的UC患者服用美沙拉明的药物，而且还没有已知的药物相互作用，但它还没有与美沙拉明联合进行正式测试。 所有潜在的研究参与者将获得一份IRB批准的知情同意进行审查。拒绝参与或退出研究的受试者将得到不带偏见的治疗。在研究开始之前，知情同意必须经过NCI、DCP、联合体牵头组织和西京医院IRB的审查和批准。专业翻译专家将把同意书翻译成中文。 12名受试者将被随机分配到每天服用黄连素500 mg 2次的药物组，4名受试者将被分配到安慰剂组，样本大小为16人。最多18名受试者将考虑到2名患者的自然减员。所有18名受试者都将在基线和三个月后进行结肠镜检查，每个人都有正常结肠粘膜和任何炎症性病灶的活检。 将通过为每个参与者分配一个数字ID来维护机密性。所有文件在传输前都将被取消身份识别。数据将由研究统计师根据标准操作程序进行管理，这些操作程序符合DCP数据管理要求的指南，并遵循西北大学向NCI癌症预防部门备案的数据管理计划。来源数据将由临床研究服务部进行核实。 临床数据将通过电子邮件报告给西北大学。西京医院的首席调查员(PI)将负责发送这些信息。西北大学以电子方式将数据输入西北大学的Notis远程数据捕获(OC-RDC)基于Web的应用程序(如果可用)。在中国政府批准后，PI将负责将组织切片运送给西北大学病理核心中心的一名确定的调查员进行额外的组织学审查。样本应每3-4个月分批运送一批4-5名受试者。所有样品将按照国际航空运输协会(IATA)的危险货物规定运输。

The investigators at Xijing Hospital in Xi’an, China are proposing a Phase I, double-blind, placebo-controlled, randomized trial of Berberine in ulcerative colitis (UC) patients who are in clinical remission, on Mesalamine for maintenance therapy. Patients with UC are at increased risk for developing colitis-associated cancer (CAC), a type of colorectal cancer. In light of this increased risk, annual colonoscopic surveillance with multiple biopsies is recommended. UC patients in remission are commonly prescribed Mesalamine, which typically helps control symptoms, but has no reported effect on cancer incidence. The incidence and prevalence of UC has been rising around the world over the last 50 years, indicating its emergence as a global disease. Berberine, a plant-derived substance that is available in the U.S. as a dietary supplement, is approved by the China Food and Drug Administration (CFDA) as an over-the-counter medication and is widely used to treat gastroenteritis and diarrhea. Berberine has shown antibacterial, anti-oxidative, and anti-inflammatory activity in several clinical trials and anti-carcinogenic activity in preclinical models. While there are extensive safety data for this compound, which is commonly given by physicians to UC patients on Mesalamine in China, and there are no known drug interactions, it has not formally been tested in combination with Mesalamine. All potential study participants will be given a copy of the IRB-approved Informed Consent to review. Subjects who refuse to participate or who withdraw from the study will be treated without prejudice. Prior to study initiation, the informed consent must be reviewed and approved by NCI, DCP, the Consortium Lead Organization and the IRB at Xijing Hospital. A professional translator expert will translate the consent into Chinese. Twelve subjects will be randomly assigned to the agent arm taking Berberine 500 mg 2x/day and four subjects will be assigned to the placebo arm for a sample size of 16. A maximum of 18 subjects will be enrolled to allow for attrition of 2 patients. All 18 subjects will have a colonoscopy at baseline and at three months, each with biopsies of the normal colonic mucosa and any inflammatory foci. Confidentiality will be maintained by assigning a numerical ID to each participant. All documents will be de-identified prior to transmission. Data will be managed by the study statistician, according to standard operating procedures, which meet the guidelines of DCP Requirements for Data Management and which follow the Data Management Plan that Northwestern University has on file with the Division of Cancer Prevention, NCI. Source data verification will be performed by the Department of Clinical Research Services. Clinical data will be reported to Northwestern University via E-mail. The principal investigator (PI) at Xijing hospital will be responsible for sending this information. Northwestern University enters data electronically to Northwestern University’s NOTIS Remote Data Capture (OC-RDC) web-based application, when available. The PI will be responsible for shipping tissue sections to an identified investigator at the Pathology Core of Northwestern University for additional histologic review upon approval of the Chinese government. Samples should be shipped every 3-4 months in batches of 4-5 subjects. All samples will be shipped in compliance with the International Air Transport Association (IATA) Dangerous Goods Regulations.