Pharmacokinetics and Hepatic Safety of EGCG

Phase 1

Completed

• Conditions: Uterine Fibroids
• Interventions: Dietary Supplement: Epigallocatechin gallate (EGCG); Drug: Clomiphene Citrate; Drug: Letrozole

• Registration Number: NCT04177693
• Lead Sponsor: Yale University

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2019-11-20
• Study First Submitted QC: 2019-11-22
• Study First Posted: 2019-11-26
• Study Start: 2020-11-24
• Primary Completion: 2022-01-31
• Study Completion: 2022-01-31
• Results First Submitted: 2023-01-27
• Status Verified: 2023-05
• Results First Submitted QC: 2023-05-08
• Last Update Submitted: 2023-05-08
• Results First Posted: 2023-06-05
• Last Update Posted: 2023-06-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 39

Inclusion Criteria

1. Healthy women ≥18 to ≤40 years of age with or without uterine fibroids
2. Must use a double-barrier method for contraception

Exclusion Criteria

1. Subjects using green tea/EGCG within 2 weeks prior to study enrollment
2. Known liver disease (defined as AST or ALT>2 times normal, or total bilirubin >2.5 mg/dL).
3. History of alcohol abuse (defined as >14 drinks/week) or binge drinking of ≥ 6 drinks at one time).
4. Subject using hormonal contraceptives
5. Subjects who are pregnant or breastfeeding
6. Known hypersensitivity to the study drugs
7. Any chronic disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EGCG daily alone.	Epigallocatechin gallate (EGCG)	EGCG daily alone. 800mg
EGCG with clomiphene citrate	Epigallocatechin gallate (EGCG)	EGCG 800 mg daily with clomiphene citrate 100mg for 5 days.
EGCG with clomiphene citrate	Clomiphene Citrate	EGCG 800 mg daily with clomiphene citrate 100mg for 5 days.
EGCG with letrozole	Epigallocatechin gallate (EGCG)	EGCG 800mg daily with letrozole 5mg for 5 days.
EGCG with letrozole	Letrozole	EGCG 800mg daily with letrozole 5mg for 5 days.

Primary Outcome Measures

Name	Time	Method
Changes in Epigallocatechin Gallate (EGCG)	Baseline, and Visit 4 (end of study, up to 40 days)	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.
Changes in Epigallocatechin (EGC)	Baseline, and Visit 4 (end of study, up to 40 days)	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.
Changes in Epicatechin Gallate(ECG)	Baseline, and Visit 4 (end of study, up to 40 days)	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Johns Hopkins Medicine; 🇺🇸 Baltimore, Maryland, United States