Pharmacokinetics and Hepatic Safety of EGCG

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

Study Overview

• Status: Completed
• Conditions: Uterine Fibroids
• Intervention / Treatment: Dietary supplement: Epigallocatechin gallate (EGCG); Drug: Clomiphene Citrate; Drug: Letrozole

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 Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Johns Hopkins University; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); University of Chicago; University of Illinois at Chicago
• Investigators: Study Director: Esther Eisenberg, MD, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Principal Investigator: Ayman Al-Hendy, MD,PhD, University of Chicago; Study Director: James Segars, MD, Johns Hopkins University; Study Director: Hugh Taylor, MD, Yale University; Study Director: Frank Gonzales, MD, University of Illinois Chicago; Study Director: Heping Zhang, PhD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2020
• Primary Completion (Actual): January 31, 2022
• Study Completion (Actual): January 31, 2022

Study Registration Dates

• First Submitted: November 20, 2019
• First Submitted That Met QC Criteria: November 22, 2019
• First Posted (Actual): November 26, 2019

Study Record Updates

• Last Update Posted (Actual): June 5, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Muscle Tissue; Leiomyoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Antioxidants; Anticarcinogenic Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Antimutagenic Agents; Letrozole; Epigallocatechin gallate; Clomiphene; Enclomiphene; Zuclomiphene
• Other Study ID Numbers: 2000028370; 1R01HD100369-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No