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.

子宫平滑肌瘤（肌瘤）是世界范围内对妇女健康最重要的肿瘤威胁。