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

NCT05364008 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: IRB002156241R01HD100369
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Leiomyoma, Uterine

Keywords

Uterine Fibroids

Outcome Measures

Primary Outcomes (1)

• Cumulative live birth rate.

  The number of women achieving live birth.

  Up to 15 months

Secondary Outcomes (6)

• The conception rate

  Up to 6 months

• The miscarriage rate

  up to 8 months

• The change of fibroid volume

  Up to 6 months

• The change of fibroid symptom severity score

  Up to 6 months

• The change of health-related quality-of-life questionnaire score

  Up to 6 months

Study Arms (2)

Green tea extract containing 45% epigallocatechin gallate (EGCG)

EXPERIMENTAL

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

Drug: Green Tea Extract

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Green Tea Extract 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.

Also known as: EGCG (epigallocatechin gallate)

Green tea extract containing 45% epigallocatechin gallate (EGCG)

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Women of reproductive age
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.
• Baseline AMH ≥ 0.7 ng/ml.
• 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.
• Evidence of ovarian function/reserve as assessed by day 3 (+/-2 days) FSH ≤12 IU/L within one year prior to study initiation.
• In general, good health as assessed by PI, not taking any medications which could interfere with the study.
• Ability to have inseminations following hCG administration.
• If applicable, the study participant will inform their partner of trial participation.
• Male partner with total motile sperm in the ejaculate of at least 5 million sperm/ml, within one year of study initiation.
• Participant agreement to abstain from use of green tea products in any form during course of study participation in trial.

You may not qualify if:

• 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).
• Currently pregnant.
• 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.
• Undiagnosed abnormal uterine bleeding.
• Suspicious ovarian mass.
• 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.
• Known 21-hydroxylase deficiency or other enzyme defects causing congenital adrenal hyperplasia.
• Uncontrolled diabetes with HbA1c \> 6.5%
• Known significant anemia (Hemoglobin \<8 g/dL).
• History of deep venous thrombosis, pulmonary embolus, or cerebrovascular event.
• Known heart disease (New York Heart Association Class II or higher).
• Known Liver disease (defined as AST or ALT\>2 times normal, or total bilirubin \>2.5 mg/dL).
• Known Renal disease (defined as BUN \>30 mg/dL or serum creatinine \> 1.4 mg/dL).
• History of, or suspected cervical carcinoma, endometrial carcinoma or breast carcinoma.
• History of alcohol abuse (defined as \>14 drinks/week) or binge drinking of ≥ 6 drinks at one time).

Sponsors & Collaborators

• University of Chicago: collaborator
• Yale University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• University of Illinois at Chicago: collaborator
• Johns Hopkins University: collaborator

Study Sites (4)

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

New Haven, Connecticut, 06520, United States

Location

University of Illinois at Chicago College of Medicine

Chicago, Illinois, 60612, United States

Location

University of Chicago, Department of Obstetrics and Gynecology

Chicago, Illinois, 60637, United States

Location

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

Baltimore, Maryland, 21205, United States

Location

Related Publications (1)

• 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.

  PMID: 38216200 DERIVED

Related Links

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

MeSH Terms

Conditions

Leiomyoma

Interventions

Tea; epigallocatechin gallate

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Plant Preparations; Biological Products; Complex Mixtures; Beverages; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• David Weinberg, PhD

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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind masking.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Susan Dwight Bliss Professor of Biostatistics and Director of Yale Collaborative Center for Statistics in Science

Model Details: Two-arm parallel assignment (with 3:1 ratio)

Study Record Dates

• First Submitted: April 22, 2022
• First Posted: May 6, 2022
• Study Start: January 5, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: data to become available in 2026
• Access Criteria: Not available at this time

Locations

US (4)