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: 10480843
• 负责人: Valerie Lynn Baker
• 金额: $ 18.96万
• 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/10480843
• 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

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.

子宫肌瘤（肌瘤）是对全世界妇女健康最重要的肿瘤威胁， 对有色人种女性的影响尤为严重，是导致不孕的一个重要原因。壁内和粘膜下 与未受影响的女性相比，肌瘤会降低怀孕的可能性（RR=0.3-0.7）。手术切除 肌瘤具有高复发率和常见的术后后果（例如粘连）。 迫切需要创新、有效、非激素、非手术的生育治疗方案 患有可能会扭曲子宫腔的肌瘤的女性。我们的长期目标是开发新型非激素 子宫肌瘤的治疗。绿茶儿茶素，例如表没食子儿茶素没食子酸酯 (EGCG) 在食用期间是安全的 受孕和怀孕。 EGCG 通过调节信号通路抑制肿瘤生长的关键通路 参与细胞增殖、转化、凋亡和炎症。我们的团队评估了功效并 双盲、安慰剂对照研究中 EGCG 对有症状子宫肌瘤女性的安全性 随机临床试验（NCT 01311869）。在安慰剂组中，肌瘤体积增加（24.3%）；然而， 随机接受 EGCG（800 毫克/天）治疗的患者显示肌瘤总体积显着减少（32.6%； P=0.0001）。这些数据表明 EGCG 可以减小子宫肌瘤的大小，并代表一种可能的非激素疗法 对患有子宫肌瘤并准备怀孕的女性进行治疗。本研究的目的是进行一项随机 确定 EGCG 对寻求生育的女性子宫肌瘤和随后怀孕的影响的临床试验 治疗。我们的中心假设是 EGCG 会减小子宫肌瘤的大小并增加子宫肌瘤的可能性 怀孕。为了检验这一假设，我们提出了一项安慰剂对照临床试验来评估活产 患有子宫肌瘤的不明原因不孕女性的结果。受试者将被随机分配到 口服 EGCG（800 毫克/天）与安慰剂，为期长达 7 个月，并有 3 个月的磨合期，随后进行卵巢治疗 刺激和宫内人工授精最多 4 个周期。目标#1：将确定临床疗效 EGCG 对 654 名寻求生育护理的女性进行了一项随机研究。目标#2：将决定怀孕 与安慰剂相比，接受 EGCG 治疗的寻求生育护理的女性的结果。联合体概况： 为了实现招聘目标，PI 组建了一个联盟，如 RFA-HD-19-022 中所述。耶鲁将服务 作为数据协调中心和临床中心，霍普金斯大学将协调单个 IRB 并成为临床中心。 伊利诺伊大学芝加哥分校的研究人员在 EGCG 和临床试验方面拥有丰富的经验， 将担任首席 PI。佛罗里达大学的研究人员在肌瘤临床试验方面拥有特殊的专业知识 以及具有生殖医学网络（AMIGOS、PPCOSII）经验的不孕不育治疗。 每个机构都拥有大量符合条件的患者和优秀的生育中心。影响：肌瘤代表 数百万受影响妇女不孕的一个原因，拟议的研究可能会产生巨大的积极作用 对寻求生育护理的子宫肌瘤女性的影响。