1/4 Reproductive Medicine Collaborative Consortium: a randomized placebo-controlled trial of EGCG to improve fertility in women with uterine fibroids

1/4 生殖医学协作联盟：一项 EGCG 改善子宫肌瘤女性生育能力的随机安慰剂对照试验

• 批准号: 10025598
• 负责人: Valerie Lynn Baker
• 金额: $ 19.72万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-26 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10025598
• 关键词: Address; Adhesions; Affect; Age; Apoptosis; Biological Markers; Biopsy; Birth Rate; Caring; Catechin; Cell Proliferation; Chicago; Clinical Trials; Clomiphene; Color; Conceptions; Controlled Clinical Trials; Data; Data Coordinating Center; Double-Blind Method; Endometrial; Endometrium; Epigallocatechin Gallate; Evaluation; Excision; Fertility; Fibroid Tumor; Florida; Follicle Stimulating Hormone; Goals; Green tea; Health; Illinois; Infertility; Inflammation; Institution; Institutional Review Boards; Intention; Lead; Letrozole; Live Birth; Medical; Menopause; Menstruation; Neoplasm Metastasis; Oral; Outcome; Outcome Measure; Ovarian Cycles; Ovarian Stimulations; Pathway interactions; Patients; Placebos; Postoperative Period; Pregnancy; Pregnancy Outcome; Public Health; Quality of life; Questionnaires; Randomized; Randomized Clinical Trials; Recurrence; Reproductive Medicine; Research; Research Personnel; Running; Safety; Serum; Signal Pathway; Teratogenic effects; Testing; Ultrasonography; Universities; Uterine Fibroids; Uterine cavity; Woman; Women' s Health; aged; arm; clinical efficacy; clinical research site; cost effective; experience; fertility improvement; fertility preservation; health disparity; health related quality of life; hormone therapy; idiopathic infertility; improved; infertility treatment; innovation; intrauterine insemination; neoplastic; novel; placebo group; polyphenol; prevent; primary outcome; randomized placebo controlled trial; randomized placebo-controlled clinical trial; recruit; reproductive; symptomatic improvement; treatment duration; treatment trial; tumor growth

Uterine leiomyomas (fibroids) are the most important neoplastic threat to women’s health worldwide, disproportionately affect women of color and are a significant cause of infertility. Intramural and submucosal fibroids reduce the likelihood of pregnancy (RR=0.3-0.7) compared to unaffected women. Surgical removal of fibroids is afflicted with high recurrence rates and frequent postoperative consequences such as adhesions. There is a critical need for innovative effective, non-hormonal, non-surgical fertility treatment options for women with fibroids that may distort the uterine cavity. Our long-term goal is to develop novel non-hormonal treatments for uterine fibroids. Green tea catechins, such as epigallocatechin gallate (EGCG) is safe during conception and pregnancy. EGCG inhibits key pathways of tumor growth by modulating signaling pathways involved in cell proliferation, transformation, apoptosis and inflammation. Our team evaluated the efficacy and safety of EGCG in women with symptomatic uterine fibroids in a double-blinded, placebo-controlled randomized clinical trial (NCT 01311869). In the placebo group, fibroid volume increased (24.3%); however, patients randomized to EGCG (800 mg/day) showed significant reduction in total fibroid volume (32.6%; P=0.0001). These data indicate that EGCG reduces fibroid size and represents a possible non-hormonal treatment for women with fibroids pursuing pregnancy. The objective of this study is to conduct a randomized clinical trial to determine the effect of EGCG on fibroids and subsequent pregnancy in women seeking fertility treatment. Our central hypothesis is that EGCG will reduce fibroid size and increase the likelihood of pregnancy. To test this hypothesis, we propose a placebo-controlled clinical trial to evaluate live birth outcomes for women with unexplained infertility who have uterine fibroids. Subjects will be randomized to either oral EGCG (800mg/day) vs. placebo for up to 7 months with a 3-month run-in period followed by ovarian stimulation and intrauterine insemination for up to 4 cycles. Aim #1: Will determine the clinical efficacy of EGCG in a randomized study in 654 women pursuing fertility care. Aim #2: Will determine pregnancy outcomes in women seeking fertility care treated with EGCG compared to placebo. Overview of consortium: To meet recruitment goals, the PIs have formed a consortium as described in RFA-HD-19-022. Yale will serve as the data coordinating center and a clinical site, Hopkins will coordinate the single IRB and be a clinical site. Investigators at University of Illinois at Chicago have extensive experience with EGCG and clinical trials and will serve as lead PI. Investigators at the University of Florida have special expertise in clinical trials for fibroids and infertility treatment with prior experience in the Reproductive Medicine Network (AMIGOS, PPCOSII). Each institution has high volume of eligible patients and an excellent fertility center. Impact: Fibroids represent a cause of infertility for millions of affected women and the proposed research could have an immense positive impact on women with uterine fibroids that are seeking fertility care.

子宫平滑肌瘤（纤维）是对全球妇女健康的最重要的肿瘤威胁， 不成比例地影响有色女性，是不育的重要原因。壁内和粘膜下 与未受影响的妇女相比，纤维降低了怀孕的可能性（RR = 0.3-0.7）。手术去除 肌瘤患者患有高复发率和经常发生的后果，例如广告。 迫切需要创新有效的，非激素，非手术生育治疗选择 具有纤维的妇女可能会扭曲子宫腔。我们的长期目标是开发新颖的非荷尔蒙 子宫纤维的治疗方法。绿茶儿茶素，例如epigallocatechin Gallate（EGCG）是安全的 构思和怀孕。 EGCG通过调节信号通路抑制肿瘤生长的关键途径 参与细胞增殖，转化，凋亡和炎症。我们的团队评估了效率和 EGCG在有症状子宫纤维的女性中的安全性，由双眼，安慰剂控制 随机临床试验（NCT 01311869）。在安慰剂组中，肌瘤的体积增加（24.3％）；然而， 随机分配给EGCG的患者（800 mg/day）显示总肌瘤量显着降低（32.6％； p = 0.0001）。这些数据表明EGCG降低了纤维化的大小，代表可能的非激素 fibroads的妇女进行怀孕的治疗。这项研究的目的是进行随机 临床试验以确定EGCG对寻求生育妇女的纤维和随后怀孕的影响 治疗。我们的中心假设是EGCG将减少纤维尺寸，并增加 怀孕。为了检验该假设，我们提出了一项安慰剂对照的临床试验来评估活产 具有子宫纤维的意外不孕症的女性的结果。受试者将被随机分为 口服EGCG（800mg/天）与安慰剂最多7个月，持续3个月，然后是卵巢 刺激和插入的授精，可用于多达4个周期。目标＃1：将确定 EGCG在一项在654名寻求生育护理的妇女的随机研究中。目标2：将确定怀孕 与安慰剂相比，寻求用EGCG治疗生育的妇女的结果。财团概述： 为了满足招聘目标，PIS已形成了一个财团，如RFA-HD-19-022中所述。耶鲁将服务 作为数据协调中心和临床部位，霍普金斯将协调单个IRB并成为临床部位。 伊利诺伊大学芝加哥大学的调查人员在EGCG和临床试验方面拥有丰富的经验 将用作铅pi。佛罗里达大学的研究人员在纤维临床试验方面具有特殊专业知识 和不孕治疗，具有生殖医学网络（Amigos，ppcosii）的先前经验。 每个机构都有大量合格的患者和出色的生育中心。影响：肌瘤代表 数以百万计的受影响妇女和拟议的研究可能具有巨大积极的原因 对寻求生育护理的子宫纤维的女性的影响。