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

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 - 应用 4/4

• 批准号: 10477364
• 负责人: Hugh Smith Taylor
• 金额: $ 34.47万
• 依托单位: YALE 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/10477364
• 关键词: Address; Adhesions; Affect; Age; Apoptosis; Biological Markers; Biopsy; Birth Rate; Caring; Catechin; Cell Proliferation; Chicago; Clinical Trials; Clomiphene; 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; Placebo Control; 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; Universities; Uterine Fibroids; Uterine cavity; Woman; Women' s Health; aged; arm; clinical efficacy; clinical research site; cost effective; efficacy evaluation; 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; ultrasound; women of color

Abstract 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 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. In the placebo group, fibroid volume increased; however, patients randomized to EGCG (800 mg/day) showed significant reduction in total fibroid volume. 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 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. We will determine the clinical efficacy of EGCG in a randomized study in 654 women pursuing fertility care; and determine pregnancy outcomes in women seeking fertility care treated with EGCG compared to placebo. To meet recruitment goals, the PIs have formed a consortium. 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. Each institution has high volume of eligible patients and an excellent fertility center. The proposed research will have an immense positive impact on women with uterine fibroids that are seeking fertility care.

摘要 子宫平滑肌瘤（纤维瘤）是全世界妇女健康最重要的肿瘤威胁， 不成比例地影响有色人种妇女，是不孕不育的重要原因。壁内和粘膜下 与未受影响的妇女相比，子宫肌瘤降低了怀孕的可能性。手术切除肌瘤是 具有高复发率和频繁的术后后果如粘连。有一个 迫切需要创新的有效的，非激素，非手术生育治疗方案的妇女， 子宫肌瘤可能会扭曲子宫腔。我们的长期目标是开发新的非激素治疗方法， 子宫肌瘤绿色茶儿茶素，如表没食子儿茶素没食子酸酯（EGCG）在受孕期间是安全的， 怀孕表没食子儿茶素没食子酸酯通过调节细胞内信号通路抑制肿瘤生长的关键途径 增殖、转化、凋亡和炎症。我们的团队评估了EGCG的有效性和安全性 在一项双盲、安慰剂对照的随机临床试验中，在 安慰剂组，肌瘤体积增加;然而，随机分配至EGCG（800 mg/天）组的患者显示， 总肌瘤体积显著减少。这些数据表明，表没食子儿茶素没食子酸酯减少纤维瘤的大小， 一种可能的非激素治疗妇女肌瘤追求怀孕。本研究的目的是 进行一项随机临床试验，以确定EGCG对子宫肌瘤和随后怀孕的影响， 寻求生育治疗的妇女。我们的中心假设是，表没食子儿茶素没食子酸酯将减少子宫肌瘤的大小和增加 怀孕的可能性。为了验证这一假设，我们提出了一个安慰剂对照的临床试验，以评估生活 患有子宫肌瘤的不明原因不孕症妇女的生育结果。受试者将随机 口服表没食子儿茶素没食子酸酯与安慰剂，持续7个月，3个月导入期，随后进行卵巢刺激 子宫内人工授精最多4个周期。我们将确定表没食子儿茶素没食子酸酯的临床疗效， 在654名寻求生育护理的妇女中进行的随机研究;并确定寻求 与安慰剂相比，用EGCG治疗的生育护理。为了达到招聘目标，PI已经成立了一个 财团耶鲁大学将作为数据协调中心和临床研究中心，霍普金斯将协调单一的 IRB和临床研究中心。伊利诺伊大学芝加哥分校的研究人员在以下方面有丰富的经验： EGCG和临床试验，并将担任首席PI。佛罗里达大学的调查人员有特别的 具有子宫肌瘤和不孕症治疗临床试验的专业知识，并具有生殖医学方面的经验 网络每个机构都有大量符合条件的患者和优秀的生育中心。拟议 研究将对寻求生育护理的子宫肌瘤妇女产生巨大的积极影响。