CLINICAL TRIAL / NCT05364008
FRIEND: Fibroids and Unexplained Infertility Treatment With Epigallocatechin Gallate; A Natural CompounD in Green Tea
- Interventional
- Active
- NCT05364008
Contact Information
- Hiba Siblini
Fibroids and Unexplained Infertility Treatment With Epigallocatechin Gallate; A Natural CompounD in Green Tea (FRIEND)
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.
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.
Gender
Female
Age Group
18 Years to 40 Years
Accepting Healthy Volunteers
No
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.