Uterine Fibroids
Conditions
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.
Interventions
DIETARY_SUPPLEMENTEpigallocatechin gallate (EGCG)
800 mg (4 capsules) of EGCG (green tea extract), taken orally on a daily basis for up to 2 months
DRUGClomiphene Citrate
100 mg for 5 days
DRUGLetrozole
5 mg for 5 days
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Illinois at Chicago
Johns Hopkins University
University of Chicago
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
The 36 women will be randomized to one of the following groups: 1. EGCG daily alone. 2. EGCG daily with clomiphene citrate 100mg for 5 days. 3. EGCG daily with letrozole 5mg for 5 days.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Changes in Estrogen (E2) | Baseline, and Visit 4 (end of study, up to 40 days) | Changes in Estrogen (E2) 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 Total Bilirubin | Baseline, and Visit 4 (end of study, up to 40 days) | Changes in total bilirubin between the 3 groups. |
| 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. |
| 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 |
| 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 Alkaline Phosphatase | Baseline, and Visit 4 (end of study, up to 40 days) | Changes in Alkaline Phosphatase between the 3 groups. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| EGCG Daily Alone. EGCG daily alone. 800mg
Epigallocatechin gallate (EGCG): 800 mg (4 capsules) of EGCG (green tea extract), taken orally on a daily basis for up to 2 months | 16 |
| EGCG With Clomiphene Citrate EGCG 800 mg daily with clomiphene citrate 100mg for 5 days.
Epigallocatechin gallate (EGCG): 800 mg (4 capsules) of EGCG (green tea extract), taken orally on a daily basis for up to 2 months
Clomiphene Citrate: 100 mg for 5 days | 11 |
| EGCG With Letrozole EGCG 800mg daily with letrozole 5mg for 5 days.
Epigallocatechin gallate (EGCG): 800 mg (4 capsules) of EGCG (green tea extract), taken orally on a daily basis for up to 2 months
Letrozole: 5 mg for 5 days | 12 |
| Total | 39 |
Baseline characteristics
| Characteristic | Total | EGCG Daily Alone. | EGCG With Clomiphene Citrate | EGCG With Letrozole |
|---|---|---|---|---|
| Age, Continuous | 28.8 years STANDARD_DEVIATION 6.3 | 29.6 years STANDARD_DEVIATION 6.3 | 27.2 years STANDARD_DEVIATION 6.6 | 29.3 years STANDARD_DEVIATION 6.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 2 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 14 Participants | 9 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 2 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 23 Participants | 11 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 39 Participants | 16 Participants | 11 Participants | 12 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 11 | 0 / 12 |
| other Total, other adverse events | 2 / 16 | 4 / 11 | 6 / 12 |
| serious Total, serious adverse events | 0 / 16 | 0 / 11 | 0 / 12 |
Outcome results
Primary
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.
Time frame: Baseline, and Visit 4 (end of study, up to 40 days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EGCG Daily Alone. | Changes in Epicatechin Gallate(ECG) | 7.6 nM |
| EGCG With Clomiphene Citrate | Changes in Epicatechin Gallate(ECG) | 64.1 nM |
| EGCG With Letrozole | Changes in Epicatechin Gallate(ECG) | 60.3 nM |
p-value: 0.202Kruskal-Wallis
Primary
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.
Time frame: Baseline, and Visit 4 (end of study, up to 40 days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EGCG Daily Alone. | Changes in Epigallocatechin (EGC) | -58.9 nM |
| EGCG With Clomiphene Citrate | Changes in Epigallocatechin (EGC) | 8.9 nM |
| EGCG With Letrozole | Changes in Epigallocatechin (EGC) | 35.4 nM |
p-value: 0.613Kruskal-Wallis
Primary
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.
Time frame: Baseline, and Visit 4 (end of study, up to 40 days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| EGCG Daily Alone. | Changes in Epigallocatechin Gallate (EGCG) | 5.8 nM |
| EGCG With Clomiphene Citrate | Changes in Epigallocatechin Gallate (EGCG) | 256.3 nM |
| EGCG With Letrozole | Changes in Epigallocatechin Gallate (EGCG) | 86.4 nM |
p-value: 0.112Kruskal-Wallis
Secondary
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.
Time frame: Baseline, and Visit 4 (end of study, up to 40 days)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EGCG Daily Alone. | Change in Serum Folate Level Between DHFR-Wild Type (WT) Group and DHFR-Hetero or Homo Group. | -3.9 ng/mL | Standard Deviation 4.3 |
| EGCG With Clomiphene Citrate | Change in Serum Folate Level Between DHFR-Wild Type (WT) Group and DHFR-Hetero or Homo Group. | -2.1 ng/mL | Standard Deviation 3.2 |
p-value: 0.24t-test, 2 sided
Secondary
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
Time frame: Baseline, and Visit 4 (end of study, up to 40 days)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EGCG Daily Alone. | Change in Serum Folate Level Between MTHFR1298-Wild Type (WT) Group and MTHFR1298-Hetero Group | -1.5 ng/mL | Standard Deviation 3 |
| EGCG With Clomiphene Citrate | Change in Serum Folate Level Between MTHFR1298-Wild Type (WT) Group and MTHFR1298-Hetero Group | -3.8 ng/mL | Standard Deviation 3.7 |
p-value: 0.07t-test, 2 sided
Secondary
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
Time frame: Baseline, and Visit 4 (end of study, up to 40 days)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EGCG Daily Alone. | Change in Serum Folate Level Between MTHFR677-Wild Type (WT) Group and MTHFR677-Hetero Group | -3.2 ng/mL | Standard Deviation 4.1 |
| EGCG With Clomiphene Citrate | Change in Serum Folate Level Between MTHFR677-Wild Type (WT) Group and MTHFR677-Hetero Group | -2.0 ng/mL | Standard Deviation 3 |
p-value: 0.372t-test, 2 sided
Secondary
Changes in Alkaline Phosphatase
Changes in Alkaline Phosphatase between the 3 groups.
Time frame: Baseline, and Visit 4 (end of study, up to 40 days)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EGCG Daily Alone. | Changes in Alkaline Phosphatase | -1.5 U/L | Standard Deviation 5.4 |
| EGCG With Clomiphene Citrate | Changes in Alkaline Phosphatase | -5.6 U/L | Standard Deviation 10.2 |
| EGCG With Letrozole | Changes in Alkaline Phosphatase | -6.0 U/L | Standard Deviation 9.1 |
p-value: 0.327Kruskal-Wallis
Secondary
Changes in ALT/SGPT
Changes in alanine aminotransferase /SGPT between the 3 groups.
Time frame: Baseline, and Visit 4 (end of study, up to 40 days)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EGCG Daily Alone. | Changes in ALT/SGPT | 1.1 U/L | Standard Deviation 5.1 |
| EGCG With Clomiphene Citrate | Changes in ALT/SGPT | 4.4 U/L | Standard Deviation 11.7 |
| EGCG With Letrozole | Changes in ALT/SGPT | -1.0 U/L | Standard Deviation 7.6 |
p-value: 0.237Kruskal-Wallis
Secondary
Changes in Endometrial Thickness
Changes in endometrial thickness between the 3 groups.
Time frame: Baseline, and Visit 4 (end of study, up to 40 days)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EGCG Daily Alone. | Changes in Endometrial Thickness | -1.9 mm | Standard Deviation 4.3 |
| EGCG With Clomiphene Citrate | Changes in Endometrial Thickness | 1.4 mm | Standard Deviation 2 |
| EGCG With Letrozole | Changes in Endometrial Thickness | 0.6 mm | Standard Deviation 2.7 |
p-value: 0.146Kruskal-Wallis
Secondary
Changes in Estrogen (E2)
Changes in Estrogen (E2) between the 3 groups.
Time frame: Baseline, and Visit 4 (end of study, up to 40 days)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EGCG Daily Alone. | Changes in Estrogen (E2) | -50.9 pg/mL | Standard Deviation 122.4 |
| EGCG With Clomiphene Citrate | Changes in Estrogen (E2) | -49.4 pg/mL | Standard Deviation 76.6 |
| EGCG With Letrozole | Changes in Estrogen (E2) | -50.2 pg/mL | Standard Deviation 127.9 |
p-value: 0.633Kruskal-Wallis
Secondary
Changes in Total Bilirubin
Changes in total bilirubin between the 3 groups.
Time frame: Baseline, and Visit 4 (end of study, up to 40 days)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EGCG Daily Alone. | Changes in Total Bilirubin | 0.1 mg/dL | Standard Deviation 0.2 |
| EGCG With Clomiphene Citrate | Changes in Total Bilirubin | 0 mg/dL | Standard Deviation 0 |
| EGCG With Letrozole | Changes in Total Bilirubin | 0 mg/dL | Standard Deviation 0.1 |
p-value: 0.508Kruskal-Wallis