Pharmacokinetics and Hepatic Safety of EGCG

Study Overview
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Brief Summary
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A trial to assess the pharmacokinetics and hepatic safety of EGCG in women with and without uterine fibroids.

Detailed Description
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This will be a randomized, multi-center, pharmacokinetics and hepatic safety trial of EGCG with 36 total patients in 3 treatment arms. 36 women will be randomized to one of the following groups: EGCG daily alone, EGCG daily with clomiphene citrate and EGCG daily with letrozole. The randomization scheme will be stratified for age groups 18-29 and 30-40 and presence of uterine fibroids. The pharmacokinetics and hepatic safety of EGCG with clomiphene citrate and letrozole are unknown. The trial conducted in women with and without fibroids will allow comparisons between these groups. The results of this study will be used to confirm hepatic safety for the larger multi-center FRIEND study.

Official Title
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Pharmacokinetics and Hepatic Safety of EGCG

Conditions
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Uterine Fibroids

Intervention / Treatment
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* Dietary Supplement: Epigallocatechin gallate (EGCG)
* Drug: Clomiphene Citrate
* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy women ≥18 to ≤40 years of age with or without uterine fibroids Must use a double-barrier method for contraception Exclusion Criteria: Subjects using green tea/EGCG within 2 weeks prior to study enrollment Known liver disease (defined as AST or ALT>2 times normal, or total bilirubin >2.5 mg/dL). History of alcohol abuse (defined as >14 drinks/week) or binge drinking of ≥ 6 drinks at one time). Subject using hormonal contraceptives Subjects who are pregnant or breastfeeding Known hypersensitivity to the study drugs Any chronic disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The 36 women will be randomized to one of the following groups: EGCG daily alone. EGCG daily with clomiphene citrate 100mg for 5 days. EGCG daily with letrozole 5mg for 5 days.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EGCG daily alone.<br>EGCG daily alone. 800mg | Dietary Supplement: Epigallocatechin gallate (EGCG)<br>* 800 mg (4 capsules) of EGCG (green tea extract), taken orally on a daily basis for up to 2 months<br>|
| Experimental: EGCG with clomiphene citrate<br>EGCG 800 mg daily with clomiphene citrate 100mg for 5 days. | Dietary Supplement: Epigallocatechin gallate (EGCG)<br>* 800 mg (4 capsules) of EGCG (green tea extract), taken orally on a daily basis for up to 2 months<br>Drug: Clomiphene Citrate<br>* 100 mg for 5 days<br>* Other names: Serophene;|
| Experimental: EGCG with letrozole<br>EGCG 800mg daily with letrozole 5mg for 5 days. | Dietary Supplement: Epigallocatechin gallate (EGCG)<br>* 800 mg (4 capsules) of EGCG (green tea extract), taken orally on a daily basis for up to 2 months<br>Drug: Letrozole<br>* 5 mg for 5 days<br>* Other names: Femara;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Epigallocatechin Gallate (EGCG) | Changes in epigallocatechin gallate (EGCG) from Visit 1 to Visit 4 (end of study). EGCG levels measured at 1 hour after taking study medication were used for both visits. | Baseline, and Visit 4 (end of study, up to 40 days) | 
| Changes in Epigallocatechin (EGC) | Changes in epigallocatechin (EGC) from Visit 1 to Visit 4 (end of study). EGC levels measured at 1 hour after taking study medication were used for both visits. | Baseline, and Visit 4 (end of study, up to 40 days) | 
| Changes in Epicatechin Gallate(ECG) | Changes in epicatechin gallate(ECG) from Visit 1 to Visit 4 (end of study). ECG levels measured at 1 hour after taking study medication were used for both visits. | Baseline, and Visit 4 (end of study, up to 40 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Total Bilirubin | Changes in total bilirubin between the 3 groups. | Baseline, and Visit 4 (end of study, up to 40 days) | 
| Changes in ALT/SGPT | Changes in alanine aminotransferase /SGPT between the 3 groups. | Baseline, and Visit 4 (end of study, up to 40 days) | 
| Changes in Alkaline Phosphatase | Changes in Alkaline Phosphatase between the 3 groups. | Baseline, and Visit 4 (end of study, up to 40 days) | 
| Changes in Estrogen (E2) | Changes in Estrogen (E2) between the 3 groups. | Baseline, and Visit 4 (end of study, up to 40 days) | 
| Changes in Endometrial Thickness | Changes in endometrial thickness between the 3 groups. | Baseline, and Visit 4 (end of study, up to 40 days) | 
| Change in Serum Folate Level Between MTHFR677-Wild Type (WT) Group and MTHFR677-Hetero Group | Change in serum folate levels between MTHFR677-Wild Type (WT) group and MTHFR677-Hetero group | Baseline, and Visit 4 (end of study, up to 40 days) | 
| Change in Serum Folate Level Between MTHFR1298-Wild Type (WT) Group and MTHFR1298-Hetero Group | Change in serum folate levels between MTHFR1298-Wild Type (WT) group and MTHFR1298-Hetero group | Baseline, and Visit 4 (end of study, up to 40 days) | 
| Change in Serum Folate Level Between DHFR-Wild Type (WT) Group and DHFR-Hetero or Homo Group. | Change in serum folate levels between DHFR-Wild Type (WT) group and DHFR-Hetero or homo group. | Baseline, and Visit 4 (end of study, up to 40 days) |