Fibroids & Infertility

(FRIEND Trial)

Recruiting in Palo Alto (17 mi)

+3 other locations

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Yale University

Must not be taking: Depo-progestins, Hormonal implants

Disqualifiers: Pregnancy, Diabetes, Heart disease, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests if a low caffeine green tea extract with high EGCG can help women aged 18-40 with fibroids get pregnant. The EGCG may shrink fibroids and improve the uterus lining, increasing pregnancy chances. EGCG, a major component of green tea, has been studied for its potential benefits in reducing uterine fibroids and improving reproductive health.

Will I have to stop taking my current medications?

The trial requires that participants not take any medications that could interfere with the study. If you are on depo-progestins or hormonal implants, a two-month period without these medications is needed before screening. Other medications are not specifically mentioned, so it's best to discuss your current medications with the study team.

What data supports the effectiveness of the treatment Green Tea Extract for uterine fibroids and infertility?

Research shows that Epigallocatechin Gallate (EGCG), a component of green tea extract, can shrink uterine fibroids and improve symptoms of benign gynecological disorders. It has been studied for its potential to reduce fibroid size and alleviate symptoms, although its role in treating infertility remains controversial. ^{1 2 3 4 5}

Is green tea extract safe for humans, particularly for women with uterine fibroids?

Research shows that taking 800 mg of green tea extract (EGCG) daily is generally safe for women, as it does not cause liver damage or affect folate levels. This suggests that green tea extract is well-tolerated in humans. ^{1 2 3 5 6}

How does the drug Green Tea Extract (EGCG) differ from other treatments for uterine fibroids and infertility?

Green Tea Extract, specifically its component EGCG, is unique because it works by reducing the size of uterine fibroids through anti-fibrotic, anti-angiogenic (preventing new blood vessel formation), and pro-apoptotic (promoting cell death) mechanisms, which are different from traditional surgical or hormonal treatments. Additionally, it is a natural compound with antioxidant properties, offering a non-invasive alternative with fewer side effects. ^{1 2 3 5 7}

Research Team

David Weinberg, PhD

Principal Investigator

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

Eligibility Criteria

This trial is for women aged 18-40 with a desire to conceive, who have been infertile for at least six months and have certain types of uterine fibroids (FIGO types 2-6). They must be regularly ovulating, have at least one open fallopian tube, and their male partner should have a sufficient sperm count. Women can't join if they've had severe endometriosis, unexplained bleeding, alcohol abuse issues or a history of blood clots.

Inclusion Criteria

I have fibroids of specific types and sizes according to FIGO classifications.

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.

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.

Exclusion Criteria

I have been diagnosed with Cushing's disease.

You regularly drink too much alcohol or have a history of binge drinking.

I have had a blood clot in my veins, lungs, or a stroke.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either low caffeine green tea extract or placebo along with Clomiphene citrate-intrauterine insemination (CC-IUI) cycle, up to 4 cycles if no pregnancy is achieved

Up to 4 cycles

Regular visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of conception and live birth outcomes

Up to 15 months

Treatment Details

Interventions

• Green Tea Extract (Polyphenol)
• Placebo (Other)

Trial Overview The study aims to see if taking green tea extract containing epigallocatechin gallate (EGCG) affects the size of fibroids in the uterus and improves chances of pregnancy and live births compared to those taking a placebo. The trial involves 200 women seeking fertility treatment.

Participant Groups

Group I: Green tea extract containing 45% epigallocatechin gallate (EGCG) Experimental Treatment 1 Intervention

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 II: Placebo Placebo Group 1 Intervention

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Yale School of Medicine Dept.of Ob/Gyn & Reproductive Sciences New Haven, CT

University of Illinois at Chicago College of Medicine Chicago, IL

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

University of Chicago, Department of Obstetrics and Gynecology Chicago, IL

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1963

Patients Recruited

3,046,000+

University of Illinois at Chicago

Collaborator

Trials

653

Patients Recruited

1,574,000+

Johns Hopkins University

Collaborator

Trials

2366

Patients Recruited

15,160,000+

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

Collaborator

Trials

2103

Patients Recruited

2,760,000+

University of Chicago

Collaborator

Trials

1086

Patients Recruited

844,000+

Findings from Research

Green tea extract, specifically epigallocatechin gallate (EGCG), significantly inhibits the growth of wild-type human leiomyoma (WT-HuLM) cells by reducing the expression and activity of the enzyme catechol-o-methyltransferase (COMT).

The antiproliferative effects of EGCG are linked to its ability to modulate multiple signaling pathways, which are less effective in cells where COMT has been silenced, indicating that COMT plays a crucial role in the mechanism of action of EGCG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Green tea extract inhibition of human leiomyoma cell proliferation is mediated via catechol-O-methyltransferase. Zhang, D., Rajaratnam, V., Al-Hendy, O., et al.[2021]

In a study of 25 women with uterine myomas, daily ingestion of green tea extract (GTE) capsules for 6 months significantly improved physical quality of life scores, as measured by the SF-12 questionnaire.

Despite the improvement in physical health, there were no significant changes in mental health scores, myoma size, or other symptoms, and no relevant side effects were reported, indicating GTE may be safe but its efficacy on myoma-related issues is limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of epigallocatechin gallate-enriched green tea extract capsules in uterine myomas: results of an observational study. Biro, R., Richter, R., Ortiz, M., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Antiproliferative and proapoptotic effects of epigallocatechin gallate on human leiomyoma cells. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Green Tea and Benign Gynecologic Disorders: A New Trick for An Old Beverage? [2023]

3. United States pubmed.ncbi.nlm.nih.gov

The combination of natural compounds Crila and epigallocatechin gallate showed enhanced antiproliferative effects on human uterine fibroid cells compared with single treatments. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Green tea extract inhibition of human leiomyoma cell proliferation is mediated via catechol-O-methyltransferase. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Assessing the Hepatic Safety of Epigallocatechin Gallate (EGCG) in Reproductive-Aged Women. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Effects of epigallocatechin gallate-enriched green tea extract capsules in uterine myomas: results of an observational study. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Biological and Mechanistic Characterization of Novel Prodrugs of Green Tea Polyphenol Epigallocatechin Gallate Analogs in Human Leiomyoma Cell Lines. [2018]