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

NCT ID: NCT05364008

Last Updated: 2025-07-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-05

Study Completion Date

2026-09-30

Brief Summary

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The objective of this study is to determine the effect of low caffeine green tea extract containing 45% epigallocatechin gallate (EGCG) on fibroids and subsequent pregnancy and live births in women seeking fertility treatment.

The population will consist of 50 women desirous of conceiving, ages ≥18 to ≤40 years (at time of consent), and known to have class 2-6 fibroids, according to the FIGO staging system.

Detailed Description

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The objective of this study is to conduct a randomized double-blinded clinical trial to determine the effect of low caffeine green tea extract on fibroids and subsequent pregnancy in women seeking fertility treatment. The investigators hypothesize that EGCG in low caffeine green tea extract will reduce the fibroid size, improve the quality of endometrium, and increase the likelihood of pregnancy. To test this hypothesis, the investigators propose a randomized placebo-controlled clinical trial to evaluate live birth outcomes for women with unexplained infertility who have uterine fibroids. Participants will be randomized to either oral low caffeine green tea extract (1650mg/day) vs. placebo along ovarian stimulation with clomiphene citrate and timed intrauterine insemination for up to 4 cycles.

Endpoints

Primary Endpoint:

\- Our primary endpoint is cumulative live birth rate.

Secondary Endpoints:

* The conception rate.
* The miscarriage rate.
* The change of fibroid volume, symptom severity score, and health-related quality-of-life score, from baseline to completion of treatment, and endometrial receptivity biomarkers.
* Time to pregnancy

This will be a randomized, multi-center, prospective, and double-blind clinical trial of low caffeine green tea extract versus placebo. Fifty (50) participants will be randomized via computer-generated randomization schedule to receive either:

1. low caffeine green tea extract (1650mg in 6 capsules) taken orally on a daily basis along with Clomiphene citrate-intrauterine insemination (CC-IUI) cycle, up to 4 cycles if no pregnancy is achieved. Participant will stop green tea if she becomes pregnant.

or
2. matched (smell, taste, color, texture) placebo capsules taken orally on a daily basis along with CC-IUI cycle, up to 4 cycles if no pregnancy is achieved. Participant will stop placebo if she becomes pregnant.

The randomization scheme will be on a 3:1 basis in favor of green tea extract, thus 37 participants will be assigned to the first arm (green tea extract) and 13 participants to the second arm (placebo).

Clomiphene citrate will be taken for 5 days on Day 3 +/- 2 days of the participant's cycle.

Conditions

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Leiomyoma, Uterine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Two-arm parallel assignment (with 3:1 ratio)
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double-blind masking.

Study Groups

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Green tea extract containing 45% epigallocatechin gallate (EGCG)

Low caffeine green tea extract (1650mg in 6 capsules) taken orally on a daily basis (QD) along with Clomiphene citrate-intrauterine insemination (CC\_IUI) cycle, up to 4 cycles if no pregnancy is achieved, participant will stop green tea if she becomes pregnant

Group Type EXPERIMENTAL

Green Tea Extract

Intervention Type DRUG

Green tea extract 1650 mg/day (45% EGCG) along with ovarian stimulation with clomiphene citrate and timed intrauterine insemination for up to 4 cycles.

Placebo

Placebo (1650mg in 6 capsules) matched (smell, taste, color, texture) capsules taken orally on a daily basis (QD) along with Clomiphene citrate-intrauterine insemination (CC\_IUI) cycle, up to 4 cycles if no pregnancy is achieved, participant will stop placebo if she becomes pregnant

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Placebo 1650 mg/day along with ovarian stimulation with clomiphene citrate and timed intrauterine insemination for up to 4 cycles.

Interventions

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Green Tea Extract

Green tea extract 1650 mg/day (45% EGCG) along with ovarian stimulation with clomiphene citrate and timed intrauterine insemination for up to 4 cycles.

Intervention Type DRUG

Placebo

Placebo 1650 mg/day along with ovarian stimulation with clomiphene citrate and timed intrauterine insemination for up to 4 cycles.

Intervention Type OTHER

Other Intervention Names

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EGCG (epigallocatechin gallate)

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

University of Chicago

OTHER

Sponsor Role collaborator

University of Illinois at Chicago

OTHER

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

Yale University

OTHER

Sponsor Role lead

Responsible Party

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Heping Zhang

Susan Dwight Bliss Professor of Biostatistics and Director of Yale Collaborative Center for Statistics in Science

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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David Weinberg, PhD

Role: STUDY_CHAIR

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Locations

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Yale School of Medicine Dept.of Ob/Gyn & Reproductive Sciences

New Haven, Connecticut, United States

Site Status RECRUITING

University of Illinois at Chicago College of Medicine

Chicago, Illinois, United States

Site Status RECRUITING

University of Chicago, Department of Obstetrics and Gynecology

Chicago, Illinois, United States

Site Status RECRUITING

Johns Hopkins, Division of Reproductive Science and Women's Health Research

Baltimore, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Ayman Al-Hendy, MD, PhD

Role: CONTACT

773-702-5954

Heping Zhang, PhD

Role: CONTACT

203-785-5185

Facility Contacts

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Lisa Schepisi

Role: primary

203-785-4933

Ana-Leonor Jay

Role: primary

Bridget Huepfel

Role: primary

312-355-5506

Samya EI Sayed

Role: primary

410-614-2000

References

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Al-Hendy A, Segars JH, Taylor HS, Gonzalez F, Siblini H, Zamah M, Alkelani H, Singh B, Flores VA, Christman GM, Johnson JJ, Huang H, Zhang H. Fibroids and unexplained infertility treatment with epigallocatechin gallate: a natural compound in green tea (FRIEND) - protocol for a randomised placebo-controlled US multicentre clinical trial of EGCG to improve fertility in women with uterine fibroids. BMJ Open. 2024 Jan 12;14(1):e078989. doi: 10.1136/bmjopen-2023-078989.

Reference Type DERIVED
PMID: 38216200 (View on PubMed)

Related Links

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https://ysph.yale.edu/c2s2/confirm/

Yale School of Public Health and NCHID conFIRM Consortia is to improve the care of women with disorders affecting the reproductive system

Other Identifiers

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1R01HD100369

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00215624

Identifier Type: -

Identifier Source: org_study_id

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