FRIEND: Fibroids and Unexplained Infertility Treatment With Epigallocatechin Gallate; A Natural CompounD in Green Tea
Study Details
Study Description
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 200 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 3 |
Detailed Description
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 for up to 7 months with a 3-month run in period followed by ovarian stimulation with clomiphene citrate and timed intrauterine insemination for up to 3 cycles.
Endpoints
Primary Endpoint:
- Our primary endpoint is cumulative live birth rate.
Secondary Endpoints:
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The conception rate.
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The miscarriage rate.
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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.
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Time to pregnancy
This will be a randomized, multi-center, prospective, and double-blind clinical trial of low caffeine green tea extract versus placebo. Two hundred (200) participants will be randomized via computer-generated randomization schedule to receive either:
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low caffeine green tea extract (1650mg in 6 capsules) taken orally on a daily basis (QD) for up to 7 months (including a 3-month run in period and 1 month for every Clomiphene citrate-intrauterine insemination (CC-IUI) cycle, up to 3 cycles if no pregnancy is achieved) or
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matched (smell, taste, color, texture) placebo capsules taken orally on a daily basis (QD) for up to 7 months (including a 3-month run in period and 1 month for every CC-IUI cycle, up to 3 cycles if no pregnancy is achieved.
The randomization scheme will be on a 3:1 basis in favor of green tea extract, thus 150 participants will be assigned to the first arm (green tea extract) and 50 participants to the second arm (placebo).
If no spontaneous pregnancy is achieved during the run-in period and the PI decides to proceed with CC-IUI, then Clomiphene citrate will be taken for 5 days on Day 3 +/- 2 days of the participant's cycle.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Green tea extract containing 45% epigallocatechin gallate (EGCG) Low caffeine green tea extract (1650mg in 6 capsules) taken orally on a daily basis (QD) for up to 7 months with up to 3 cycles of clomiphene citrate (CC) intrauterine insemination (IUI). |
Drug: Green Tea Extract
Green tea extract 1650 mg/day (45% EGCG) for up to 7 months with a 3-month run in period followed by ovarian stimulation with clomiphene citrate and timed intrauterine insemination for up to 3 cycles.
Other Names:
|
| Placebo Comparator: Placebo Placebo matched (smell, taste, color, texture) capsules taken orally on a daily basis (QD) for up to 7 months (including a 3-month run in period and 1 month for every CC-IUI cycle, up to 3 cycles of clomiphene citrate (CC) intrauterine insemination (IUI). |
Other: Placebo
Placebo 1650 mg/day for up to 7 months with a 3-month run in period followed by ovarian stimulation with clomiphene citrate and timed intrauterine insemination for up to 3 cycles.
|
Outcome Measures
Primary Outcome Measures
- Cumulative live birth rate. [Up to 16 months]
The number of women achieving live birth.
Secondary Outcome Measures
- The conception rate [Up to 7 months]
The number of women achieving conception
- The miscarriage rate [up to 9 months]
The number of women who have a miscarriage after conception.
- The change of fibroid volume [Up to 7 months]
The absolute change in fibroid volume (cm^3) from baseline to completion of treatment.
- The change of fibroid symptom severity score [Up to 7 months]
The absolute change in fibroid symptom severity summary scores from baseline to completion of treatment. It consists of an 8-item symptom severity scale. All items are scored on a 5-point Likert scale, ranging from "not at all" (1) to "a very great deal" (5). A high score means a worse outcome.
- The change of health-related quality-of-life questionnaire score [Up to 7 months]
The absolute change in health-related quality-of-life questionnaire summary scores from baseline to completion of treatment. It consists 29 Health-Related Quality of Life items comprising 6 domains: Concern, Activities, Energy/Mood, Control, Self-consciousness, and Sexual Function. All items are scored on a 5-point Likert scale, ranging from "none of the time" (1) to "all of the time" (5). A higher score means a worse outcome.
- Time to conception [7 months]
The time from randomization to the first date of conception found
Eligibility Criteria
Criteria
Inclusion Criteria:
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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.
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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.
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Baseline AMH ≥ 1.0 ng/ml.
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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.
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Evidence of ovarian function/reserve as assessed by day 3 (+/-2 days) FSH ≤12 IU/L within one year prior to study initiation.
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Normal or corrected thyroid function within one year of study initiation.
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Normal prolactin level within one year of study initiation.
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In general, good health as assessed by PI, not taking any medications which could interfere with the study (e.g., FSH, insulin sensitizers).
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Ability to have inseminations following hCG administration.
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If applicable, the study participant will inform their partner of trial participation.
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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.
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Exclusion Criteria:
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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).
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Currently pregnant or successful pregnancies within 12 months of initiating participation. Clinical intrauterine miscarriages prior to initiating participation: participants over 35 must wait 3 months, while participants under 35 must wait 6 months. No exclusion for biochemical pregnancies.
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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. Patients with a detectable EGCG level at the screening visit will be excluded.
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Undiagnosed abnormal uterine bleeding.
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Suspicious ovarian mass.
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Participants on oral contraceptives, 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. A one-month washout will be required for participants on oral cyclic progestins.
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Known 21-hydroxylase deficiency or other enzyme defects causing congenital adrenal hyperplasia.
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Type I or Type II diabetes mellitus.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Yale University
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- University of Chicago
- University of Illinois at Chicago
- Johns Hopkins University
Investigators
- Study Chair: Esther Eisenberg, MD, MPH, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- IRB00215624
- 1R01HD100369