CHEMOPREVENTION OF DEFLUOROMETHYLORNITHINE IN INTESTINAL BARRETTS ESOPHAGUS

脱氟甲基鸟氨酸对肠 Barrett 食管的化学预防

• 批准号: 6297036
• 负责人: Dean E. Brenner
• 金额: $ 0.02万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6297036
• 关键词: adenocarcinoma; biomarker; cell proliferation; chemoprevention; clinical research; difluoromethylornithine; esophagus disorder; gastrointestinal disorder; gastrointestinal disorder chemotherapy; human subject; human therapy evaluation; medical complication; neoplastic transformation; pathologic process

We propose a Phase IIb clinical trial of alpha-difluoromethylornithine (DFMO), a potent inhibitor of ornithine decarboxylase, a crucial enzyme in the spermine synthesis pathway which is required for cellular growth as a potential treatment to prevent the progression of Barrett's esophagus to invasive adenocarcinoma. This Phase IIb study is designed to determine whether DFMO, given in a double-blinded, placebo-controlled clinical trial will alter cellular proliferation in human subjects with dysplastic or metaplastic Barrett's esophagus. Human subjects with intestinal type Barrett's metaplasia or mild dysplasia will be treated with DFMO, 900 mg daily, or placebo in a randomized, double blinded design for 6 months. Prior, 6 months, and 13 months after treatment, endoscopy with biopsies of the Barrett's esophagus, normal esophagus, and normal gastric mucosa will be obtained and studied for surrogate endpoint biomarkers (proliferation, apoptosis, cellular morphometry, microsatellites, p53, and transforming growth factors).

我们提出了一项α-二氟甲基鸟氨酸（DFMO）的IIb期临床试验，DFMO是一种有效的鸟氨酸脱羧酶抑制剂，是细胞生长所需的精胺合成途径中的一种关键酶，作为一种潜在的治疗方法，以防止巴雷特食管进展为浸润性腺癌。 这项IIb期研究旨在确定在双盲、安慰剂对照临床试验中给予DFMO是否会改变患有发育异常或化生性巴雷特食管的人类受试者的细胞增殖。 患有肠型巴雷特化生或轻度异型增生的人类受试者将以随机、双盲设计用DFMO（每日900 mg）或安慰剂治疗6个月。治疗前、治疗后6个月和治疗后13个月，将获得Barrett食管、正常食管和正常胃粘膜的内镜检查和活检，并研究替代终点生物标志物（增殖、凋亡、细胞形态测定、微卫星、p53和转化生长因子）。