Using green tea extract to treat fibroids and improve fertility

Fibroids and Unexplained Infertility Treatment With Epigallocatechin Gallate; A Natural CompounD in Green Tea (FRIEND)

This study is testing if a green tea extract can help women with fibroids improve their chances of getting pregnant and having a healthy baby.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 40 Years
• Sex: Female
• Sponsor: Yale University (Academic / other)
• Locations: 4 sites (New Haven, Connecticut and 3 other locations)
• Trial ID: NCT05364008 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effects of low caffeine green tea extract, which contains 45% epigallocatechin gallate (EGCG), on uterine fibroids and fertility outcomes in women seeking to conceive. The study will involve 50 women aged 18 to 40 with class 2-6 fibroids, who will be randomly assigned to receive either the green tea extract or a placebo alongside fertility treatments. The primary endpoint is the cumulative live birth rate, while secondary endpoints include conception rates, miscarriage rates, and changes in fibroid volume and quality of life. The trial is designed to be randomized, double-blinded, and multi-center to ensure robust results.

Who should consider this trial

Good fit: Ideal candidates are women aged 18 to 40 with class 2-6 uterine fibroids and a history of unexplained infertility.

Not a fit: Patients with fibroids classified as FIGO type 0 or type 1, or those not seeking fertility treatment, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve fertility outcomes for women with uterine fibroids.

How similar studies have performed: While the use of green tea extract in this context is novel, other studies have explored natural compounds for similar conditions with varying degrees of success.

Eligibility criteria

Inclusion Criteria:

1. Intramural fibroids and/or subserosal fibroids that meet the criteria for FIGO types 2-6; at least one fibroid with an average diameter of at least 1 cm in three dimensions. Participants with multiple fibroids including FIGO type 0 and type 1 will be allowed only in combination with additional fibroids type 2-6.
2. Women ≥18 to ≤40 years of age, with six months or more infertility history, desirous of conceiving, regularly ovulating (defined as 9 or more menses per year), at initiation of participation. Women \< 35 years of age must have at least 12 months of infertility history.
3. Baseline AMH ≥ 0.7 ng/ml.
4. At least one open fallopian tube confirmed by hysterosalpingography (HSG), sonohysterography, or laparoscopy/hysteroscopy in the last three years preceding enrollment into the study. An uncomplicated intrauterine non-IVF pregnancy and uncomplicated delivery and postpartum course resulting in live birth within the last three years will also serve as sufficient evidence of a patent tube and normal uterine cavity as long as the participant did not have, during the pregnancy or subsequently, risk factors for Asherman's syndrome or tubal disease or other disorder leading to an increased suspicion for intrauterine abnormality or tubal occlusion.
5. Evidence of ovarian function/reserve as assessed by day 3 (+/-2 days) FSH ≤12 IU/L within one year prior to study initiation.
6. In general, good health as assessed by PI, not taking any medications which could interfere with the study.
7. Ability to have inseminations following hCG administration.
8. If applicable, the study participant will inform their partner of trial participation.
9. Male partner with total motile sperm in the ejaculate of at least 5 million sperm/ml, within one year of study initiation.
10. Participant agreement to abstain from use of green tea products in any form during course of study participation in trial.

Exclusion Criteria:

1. Participants with only intracavity uterine fibroid (FIGO Type 0 or Type 1) when not in combination with other types of fibroids (FIGO type 2-6).
2. Currently pregnant.
3. Clinical intrauterine miscarriages prior to initiating participation: participants must wait 3 months. No exclusion for biochemical pregnancies.
4. Subjects using Green Tea/EGCG within 2 weeks prior to study enrollment. Matcha (Japanese green tea), maca powder, green tea beverages and all other forms of green tea require a 2-week wash-out.
5. Undiagnosed abnormal uterine bleeding.
6. Suspicious ovarian mass.
7. Participants on depo-progestins, or hormonal implants (including Implanon). A two-month washout period will be required prior to screening for participants on these agents. Longer washouts may be necessary for certain depot contraceptive forms or implants, especially when the implants are still in place.
8. Known 21-hydroxylase deficiency or other enzyme defects causing congenital adrenal hyperplasia.
9. Uncontrolled diabetes with HbA1c \> 6.5%
10. Known significant anemia (Hemoglobin \<8 g/dL).
11. History of deep venous thrombosis, pulmonary embolus, or cerebrovascular event.
12. Known heart disease (New York Heart Association Class II or higher).
13. Known Liver disease (defined as AST or ALT\>2 times normal, or total bilirubin \>2.5 mg/dL).
14. Known Renal disease (defined as BUN \>30 mg/dL or serum creatinine \> 1.4 mg/dL).
15. History of, or suspected cervical carcinoma, endometrial carcinoma or breast carcinoma.
16. History of alcohol abuse (defined as \>14 drinks/week) or binge drinking of ≥ 6 drinks at one time).
17. Known Cushing's disease.
18. Known or suspected adrenal or ovarian androgen secreting tumors.
19. Allergy or contraindication to the treatment medications: EGCG, clomiphene citrate (CC) or hCG.
20. Couples with previous sterilization procedures (e.g., vasectomy, tubal ligation) which have been reversed.
21. Participants with untreated poorly controlled hypertension defined as a systolic blood pressure ≥ 160 mm Hg or a diastolic ≥ 100 mm Hg obtained on two measures obtained at least 60 minutes apart.
22. Participants who have undergone a bariatric surgery procedure in the recent past (\< 12 months) and are in a period of acute weight loss or have been advised against pregnancy by their bariatric surgeon.
23. Stage 3 and 4 endometriosis and endometriomas \> 3cm (as per PI discretion) .
24. Known polycystic ovarian syndrome as evidenced by anovulation or oligoovulation hirsutism and/or elevated testosterone levels, and ovarian morphology on ultrasound examination.
25. Medical conditions that are contraindications to pregnancy.

Where this trial is running

New Haven, Connecticut and 3 other locations

• Yale School of Medicine Dept.of Ob/Gyn & Reproductive Sciences — New Haven, Connecticut, United States (Recruiting)
• University of Illinois at Chicago College of Medicine — Chicago, Illinois, United States (Recruiting)
• University of Chicago, Department of Obstetrics and Gynecology — Chicago, Illinois, United States (Recruiting)
• Johns Hopkins, Division of Reproductive Science and Women's Health Research — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Study coordinator: Ayman Al-Hendy, MD, PhD

Conditions Leiomyoma, Uterine; Uterine Fibroids