Suppression of Breakthrough Bleeding in LNG-IUS Users

抑制 LNG-IUS 用户突破性出血

• 批准号: 6560852
• 负责人: ROBERT M BRENNER
• 金额: $ 39.75万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-27 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6560852
• 关键词: British Isles; Macaca mulatta; biopsy; clinical research; clinical trials; dosage; drug adverse effect; endometrium; female; gene expression; hemorrhage; hormone inhibitor; human subject; human therapy evaluation; levonorgestrel; microarray technology; morphometry; nondrug contraceptive; nonhuman therapy evaluation; patient oriented research; pharmacokinetics; progestins; reproductive system disorder chemotherapy; reproductive system pharmacology; women's health

DESCRIPTION (provided by applicant): The Mirena(c) (Leiras, OY, Finland) is an intrauterine system (IUS) that releases levonorgestrel (LNG) and provides women with highly effective contraception for 5 years. However, serious breakthrough bleeding (BTB) can occur that leads many patients to discontinue treatment. In women using subcutaneous Norplant contraception, BTB can be suppressed by intermittent antiprogestin therapy with mifepristone. NICHD has a new antiprogestin, CDB-2914, that is more potent than mifepristone. The goal of this proposal is to determine whether CDB-2914 can suppress the BTB associated with the LNG-IUS. Preclinical studies will be done first in rhesus macaques fitted with an LNG-IUS and the information gained will be transmitted to Professor Hilary Critchley, University of Edinburgh, who will select a test population of 150 women from a pool of over 400 who are being fitted annually with an LNG-IUS for contraception. The bleeding-suppressive dose and schedule of CDB-2914 that works well in macaques will be adapted for use in women. The work consists of two major aims: Aim 1: to establish an effective, bleeding-suppressive dose schedule of CDB 2914 in macaques, and to assess spatio-temporal expression of bleeding-associated factors in the endometrium. Aim 2: to conduct a randomized, placebo controlled trial to evaluate CDB-2914 suppression of BTB in women being fitted with the LNG-IUS; and for added value, to develop a questionnaire to assess acceptability of the proposed treatment to women. This proposal involves translation of the information gained from basic research with macaques into clinical practice in women within the time frame of the grant. It is essential to conduct the clinical work at the University of Edinburgh, Scotland, UK, because no clinic in the USA has such a large patient population of women being fitted with the LNG-IUS for contraception. The macaque model provides excellent predictability for human studies, and Drs. Brenner and Critchley have published collaboratively on data from macaques and women in several recent papers. The proposal brings basic scientists and clinicians together for a "bench to bedside" approach that will advance women's health and improve contraceptive technology.

描述（由申请人提供）：Mirena(c)（Leiras，OY，芬兰）是一种宫内节育系统 (IUS)，可释放左炔诺孕酮 (LNG)，为女性提供 5 年高效避孕。然而，可能会发生严重的突破性出血（BTB），导致许多患者停止治疗。对于使用皮下注射 Norplant 避孕药的女性，BTB 可以通过米非司酮间歇性抗孕激素治疗来抑制。 NICHD 有一种新的抗孕激素 CDB-2914，比米非司酮更有效。该提案的目标是确定 CDB-2914 是否可以抑制与 LNG-IUS 相关的 BTB。临床前研究将首先在配备 LNG-IUS 的恒河猴中进行，获得的信息将传输给爱丁堡大学的希拉里·克里奇利 (Hilary Critchley) 教授，他将从每年 400 多名配备 LNG-IUS 避孕的女性中选择 150 名女性进行测试。 CDB-2914 在猕猴中效果良好的止血剂量和给药方案将适用于女性。这项工作有两个主要目标： 目标 1：在猕猴中建立有效的、抑制出血的 CDB 2914 剂量方案，并评估子宫内膜中出血相关因子的时空表达。目标 2：进行一项随机、安慰剂对照试验，以评估 CDB-2914 对装有 LNG-IUS 的女性的 BTB 抑制作用；为了增加价值，制定一份调查问卷来评估妇女对拟议治疗的接受程度。该提案涉及在拨款期限内将从猕猴基础研究中获得的信息转化为女性的临床实践。 在英国苏格兰爱丁堡大学开展临床工作至关重要，因为美国没有一家诊所拥有如此多的女性患者，配备了 LNG-IUS 进行避孕。猕猴模型为人类研究提供了极好的可预测性，博士。布伦纳和克里奇利在最近的几篇论文中合作发表了有关猕猴和女性的数据。该提案将基础科学家和临床医生聚集在一起，采取“从实验室到床边”的方法，以促进妇女的健康并改进避孕技术。