Uterine Leiomyomata, also known as uterine fibroids, are non-cancer tumors found in the wall
      of the uterus or womb. Uterine fibroids are the common cause of surgery (removal of the
      uterus). African American women are 3-4 times more likely to have uterine fibroids. Currently
      there is no effective long-term medical treatment for fibroids. Hormones have been used for
      short-term therapy, but they are not used long-term because of the risk of side effects. When
      women stop receiving the hormone therapy often fibroids return. Surgery is the common
      treatment for women who are suffering from abnormal symptoms caused by fibroids. Hysterectomy
      is an effective treatment, however women cannot have children after removal of the uterus.

      Epigallocatechin Gallate (EGCG) is one of the main natural chemicals found in green tea..
      Research the investigators have done in the laboratory and in animals leads them to believe
      EGCG may decrease the growth of fibroids.

      This study is intended to determine whether EGCG will cause fibroid tumors to shrink and
      reduce fibroid related symptoms such as abnormal vaginal bleeding and pelvic discomfort.

Green Tea Extract: a Non-Surgical Alternative for Treatment of Uterine Fibroids

Leiomyoma

-  Uterine leiomyoma (also known as fibroids) are benign estrogen-dependent tumors of the
           uterine wall. Uterine fibroids are the most common tumors of the female reproductive
           tract, occurring in 20-70% of premenopausal women in the reproductive age women and
           cause multiple clinical complications such as acute and chronic pelvic pain as well as
           excessive vaginal bleeding and iron deficiency anemia, moreover they are considered as
           the leading indication for hysterectomy in reproductive age African American (AA) women.
           The impact of these serious clinical complications on women's health is tremendous.
           African American women are particularly affected as the prevalence of uterine fibroids
           is about 4 times higher in that ethnic group compared to Caucasians. Being a major
           health disparity issue, uterine fibroids appear to further diminish the quality of life
           for AA women who also suffer from higher incidence of chronic diseases such as diabetes,
           heart disease, obesity, and cancer. Currently there is no effective long-term medicinal
           treatment for this common disease. GnRH analogues are effective short medical therapy
           option. However, they are not approved for long-term (more than 3 months) because of the
           risk of irreversible bone loss and osteoporosis and other major side effects. When these
           medications are discontinued, the fibroids return to their original size with symptoms
           recurring, that is why they are FDA approved in uterine fibroids only as preoperative
           adjuvant to improve the fibroid-related iron-deficiency anemia. Surgery, usually in the
           form of hysterectomy, is the traditional treatment of women with symptomatic uterine
           fibroids. Clearly hysterectomy is an effective treatment but it precludes future
           fertility. This creates a major dilemma for women with symptomatic uterine fibroids who
           have not completed their families or have not even started a family. Problems with
           fibroids must be viewed as a public health concern as well as a major health disparity
           issue. The general public in relation to this problem must be concerned about the: (1)
           The decrease in the quality of life of women who are affected, and hence the well-being
           of the whole family; (2) Interference with inter-family dynamics and relationships.
           Decrease in productivity in the workforce/job performance. Increase in cost of health
           care caused by the more than 600,000 hysterectomies/Y in USA alone.

        -  Green Tea Extract

      This work will evaluate the utility of EGCG, green tea extract, which is a common nutritional
      supplement, in symptomatic relief of this common women's health problem. Considering the wide
      acceptability of nutritional supplements especially among African American women, the ethnic
      group most affected by uterine fibroids, this project can potentially provide an effective
      and inexpensive non-surgical alternative for management of uterine fibroids. Green tea is a
      common agent used by women for multiple purposes. Epigallocatechin gallate (EGCG) is the
      major catechin (about 80%) of green tea. EGCG exhibit several useful biological effects
      including anti-inflammatory, anti-proliferative as well as anti-oxidant effects. A study
      conducted by the United States Department of Agriculture reported that green tea has potent
      anti-cancer effects against a wide range of human cancer cells. Green tea's polyphenols, most
      notably EGCG, are considered responsible for those positive effects. Green tea polyphenols
      have also been shown to inhibit key pathways of tumor growth.

        -  Prior Human Experience with EGCG Several human clinical studies used EGCG for extended
           periods of time in which EGCG was very well tolerated with virtually no reportable side
           effects. Wolfarm and colleagues used oral EGCG 300 mg/day in cardiac patients and
           reported improved endothelial function and increased brachial artery flow-mediated
           dilation that paralleled changes in EGCG plasma concentration. reported on the
           consumption of 500-1000 mg/day of oral EGCG for 3 months which resulted in marked
           decrease in several anti-oxidative biomarkers compared to placebo. Numerous studies have
           described favorable effects of EGCG when used in overweight and obese individuals for
           extended durations. Chow et.al. reported on human use of EGCG with 30 healthy volunteers
           randomly assigned to one of the following doses of Polyphenon E (a decaffeinated green
           tea catechin mixture): 400, 800, or 1200 mg/day (10 subjects per dose group). Only
           transient mild nausea was noted in 3% of the study participants and was seen only at the
           highest study agent dose (1200 mg EGCG/day) and in the fasting condition. Doses of 800mg
           were well tolerated with no reported side effects. Grapes also contain polyphenols and
           catechins such as EGCG. EGCG is the most powerful of these catechins that accounts for
           the favorable health effects from the use of grapes extracts. Grapes polyphenols have
           been shown to inhibit key pathways of tumor growth. Grapes EGCG appear to block each
           stage of tumor-genesis by modulating signaling pathways involved in cell proliferation,
           transformation, inflammation, and oxidative stress, which are clearly involved in
           pathogenesis of various tumors including uterine fibroids. Freeze-dried table grapes
           powder has been used recently for several months in pre-and post-menopausal women at
           doses of up to 36 gm/day. This dose corresponds to about 800mg EGCG/day. This treatment
           was very well tolerated with no reported side effects. This suggests that such
           supplement can be successfully administered to women as part of life or diet
           modification programs.

        -  Preclinical Data Recent studies from our group demonstrated the ability of EGCG to
           control the proliferation and to induce apoptosis in human leiomyomata cells in vitro
           and in animal models. Our preclinical data in fibroid animal models demonstrates that
           EGCG at a dose of 1.25mg/Kg/day added to drinking water was able to induce a highly
           significant (up to 80%) shrinkage of fibroid lesions compared to untreated controls. The
           treatment was well tolerated with no detected side effects. Such daily doses of EGCG
           have been administered safely to human subjects in prior clinical trials. This effect is
           partially attributed to potent inhibitory effect of EGCG on Catechol-O-methyl
           transferase (COMT), an enzyme that we have recently linked to pathogenesis of uterine
           fibroids. In this proposal we aim to evaluate the efficacy of Epigallocatechin gallate
           (EGCG) in reducing the size of uterine fibroids and improving quality of life in women
           with symptomatic uterine fibroids, as well as assess its safety profile.

        -  We have recently demonstrated elevated levels of expression of catechol-O-methyl
           transferase (COMT) in uterine fibroids compared to adjacent normal myometrium, and
           described its important role in fibroid pathogenesis.

        -  Interestingly, recent reports demonstrated that EGCG has potent anti-COMT activity.
           These reports have shown that green tea extract intake is associated with weight loss
           due to diet-induced thermo-genesis. This effect is generally attributed to EGCG. This
           catechin is known to be capable of inhibiting COMT, which is the enzyme that degrades
           nor-epinephrine, thus stimulating thermo-genesis. The inhibition of COMT by EGCG was
           uncompetitive with respect to S-adenosylmethionine (SAM) suggesting that there is no
           direct interaction between EGCG and the SAM-binding site on the COMT, yet there was
           clear inhibition of COMT activity with increasing EGCG concentration. Additionally, the
           Vmax values for methylation were decreased. Our preliminary data also showed that EGCG
           inhibited COMT gene expression in a dose-dependent manner in human leiomyomata cells.

        -  Our hypothesis is that the use of the "EGCG" as a nutritional supplement will decrease
           the size of uterine fibroids and improve fibroids-related clinical symptoms in women
           resulting in a significant improvement in their quality of life.

        -  This work will evaluate the utility of a common nutritional supplement in symptomatic
           relief of a very common women's health problem. Considering the availability, lower
           cost, as well as the wide acceptability of nutritional supplements, this project can
           potentially provide an inexpensive non-surgical alternative for management of uterine
           fibroids which would have a major impact on health of women from all ethnic groups.

EGCG ( Green Tea extract)

Brown rice pills

Principal Investigator

40 subjects will receive 800 mg EGCG orally per day for 6 months versus 40 subjects will receive Brown Rice pill for 6 months

40 subjects will receive 800 mg brown rice pills orally per day for 6 months versus 40 subjects will receive EGCG capsule for 6 months

Green Tea Extract: a Non-Surgical Alternative for Treatment of Uterine Fibroids

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Not accepting

Trial Timing

What is this trial about?

What are the participation requirements?