3/4, University of Illinois at Chicago Clinical Site- Reproductive Medicine Collaborative Consortium: A randomized placebo-controlled trial of EGCG to improve fertility in women with uterine fibroids

3/4，伊利诺伊大学芝加哥分校临床中心 - 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: 10878669
• 负责人: Ayman Al-Hendy
• 金额: $ 31.16万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 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/10878669
• 关键词: Address; Adhesions; Affect; Age; Apoptosis; Biological Markers; Biopsy; Caring; Catechin; Cell Proliferation; Chicago; Clinical Trials; Clomiphene; Conceptions; Controlled Clinical Trials; Data; Data Coordinating Center; Double-Blind Method; Eligibility Determination; Endometrial; Endometrium; Epigallocatechin Gallate; Evaluation; Excision; Fertility; Fibroid Tumor; Florida; Follicle Stimulating Hormone; Friends; Goals; Green tea; Health; Illinois; Infertility; Inflammation; Institution; Institutional Review Boards; Intention; Invaded; Lead; Letrozole; Live Birth; Live-Birth Pregnancy Rate; Medical; Menopause; Menstruation; Neoplasm Metastasis; Oral; Outcome; Outcome Measure; Ovarian Cycles; Ovarian Stimulations; Ovulation; Pathway interactions; Patients; Placebo Control; Placebos; Postoperative Period; Pregnancy; Pregnancy Outcome; Public Health; Quality of life; Questionnaires; Randomized; Recurrence; Reproductive Medicine; Research; Research Personnel; Running; Safety; Serum; Signal Pathway; Submucosa; 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; randomized, clinical trials; 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 (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 @ 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.

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（RR=0.3-0.7）。手术切除 纤维瘤具有高复发率和频繁的术后后果如粘连。 迫切需要创新的有效的、非激素的、非手术的生育治疗选择， 患有可能扭曲子宫腔的纤维瘤的妇女。我们的长期目标是开发新的非激素 子宫肌瘤的治疗方法绿色茶儿茶素，如表没食子儿茶素没食子酸酯（EGCG）是安全的， 怀孕和怀孕。表没食子儿茶素没食子酸酯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。我们的团队评估了疗效， 在一项双盲、安慰剂对照的研究中， 随机临床试验（NCT 01311869）。在安慰剂组中，肌瘤体积增加（24.3%）;然而， 随机分配至EGCG组（800 mg/天）的患者显示总肌瘤体积显著减少（32.6%; P=0.0001）。这些数据表明，表没食子儿茶素没食子酸酯减少子宫肌瘤的大小，并代表了一个可能的非激素 治疗患有子宫肌瘤的妇女寻求怀孕。本研究的目的是进行一项随机 临床试验，以确定影响的表没食子儿茶素没食子酸酯对纤维瘤和随后怀孕的妇女寻求生育 治疗我们的中心假设是，表没食子儿茶素没食子酸酯将减少子宫肌瘤的大小，并增加 怀孕为了验证这一假设，我们提出了一个安慰剂对照的临床试验，以评估活产 患有子宫肌瘤的不明原因不孕症女性的结局。受试者将随机 口服表没食子儿茶素没食子酸酯（800毫克/天）与安慰剂，长达7个月，有3个月的导入期，然后卵巢 刺激和子宫内授精长达4个周期。目的#1：将确定 在654名寻求生育护理的妇女中进行的一项随机研究中的EGCG。目标#2：决定怀孕 与安慰剂相比，寻求生育护理的妇女接受EGCG治疗的结果。联合体概况： 为实现招募目标，PI已组建了一个联盟，如RFA-HD-19-022所述。耶鲁将担任 作为数据协调中心和临床研究中心，霍普金斯将协调单个IRB并成为临床研究中心。 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， 将担任首席私家侦探佛罗里达大学的研究人员在纤维瘤的临床试验方面有特殊的专业知识 在生殖医学网络（AMIGOS，PPCOS II）中具有先前经验的不孕症治疗。 每个机构都有大量符合条件的患者和优秀的生育中心。影响：肌瘤代表 这是数百万受影响妇女不孕的原因，拟议中的研究可能会产生巨大的积极影响。 对正在寻求生育护理的子宫肌瘤妇女的影响。