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| ID | Type | Description | Link |
|---|---|---|---|
| R21AT002297 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Center for Complementary and Integrative Health (NCCIH) | NIH |
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This study will determine the effects of St. John's wort, a common herbal remedy, on metabolism of the female contraceptive hormone levonorgestrel.
In the last decade, St. John's wort has become one of the most commonly used botanicals. Levonorgestrel is a form of progesterone, a female hormone involved in conception. It can be given as both a pill and an injection and is used for contraception and for the treatment of endometriosis. However, evidence suggests that St. John's wort may reduce the effectiveness of the contraceptive hormone levonorgestrel. This study will determine whether interactions between St. John's wort and levonorgestrel reduce the effectiveness of the hormone. This study will also determine whether a higher dose of levonorgestrel will override the effects of St. John's wort.
All participants will receive a single dose of levonorgestrel between Days 9 and 12 of their first menstrual cycle after entering this study. Blood and urine collection will occur immediately after the levonorgestrel is given and every week until participants' next menstrual cycle to determine the levels of reproductive hormones in participants' bodies.
At the beginning of participants' next menstrual cycle, they will be randomly assigned to one of four groups and receive either St. John's wort or placebo for 6 weeks. Group 1 will receive a placebo; Groups 2 and 3 will receive a standard dose of St. John's wort (900 mg per day); and Group 4 will receive an increased dose of St. John's wort (1500 mg per day). After 6 weeks, Groups 1, 2, and 4 will receive 150 mcg levonorgestrel; and Group 3 will receive 225 mcg levonorgestrel. Blood and urine collection will occur immediately after levonorgestrel is given and every week until participants' next menstrual cycle.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Levonorgestrel 1.5 with Placebo Herb | Placebo Comparator | This group had baseline pharmacokinetic studies after an oral dose of levonorgestrel (LNG) 1.5 mg, then took a placebo herb daily for 4-6 weeks, during which time pharmacokinetic studies were repeated after an oral dose of LNG 1.5 mg |
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| Levonorgestrel 1.5 with SJW 900 mg | Active Comparator | This group had baseline pharmacokinetic studies after an oral dose of levonorgestrel (LNG) 1.5 mg, then took St. John's Wort (SJW) 900 mg a Day orally for 4-6 weeks, during which time pharmacokinetic studies were repeated after an oral dose of LNG 1.5 mg |
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| Levonorgestrel 2.25 with SJW 900 mg | Active Comparator | This group had baseline pharmacokinetic studies after an oral dose of levonorgestrel (LNG) 1.5 mg, then took a St. Johns's Wort 300 mg capsules three times daily for 4-6 weeks, during which time pharmacokinetic studies were repeated after an oral dose of LNG 2.25 mg |
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| Levonorgestrel 1.5 with SJW 1500 mg | Active Comparator | This group had baseline pharmacokinetic studies after an oral dose of levonorgestrel (LNG) 1.5 mg, then took a St. Johns's Wort 300 mg capsules five times daily for 4-6 weeks, during which time pharmacokinetic studies were repeated after an oral dose of LNG 1.5 mg |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo Control (Placebo Herb) | Dietary Supplement | Placebo herb three times daily (ground cellulose) for 4-6 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration Versus Time Curve for 0 to 24 Hours After Drug Administration, Done Between Days 9 and 12 of the Menstrual Cycle at Time 1 (Before) and Time 2 (During Treatment With St. John's Wort or Placebo) | Pharmacokinetic studies were done between Days 9-12 of the menstrual cycle at Time 1 (baseline, before any treatment with herb or placebo), and at Time 2 (intervention, after treatment with herb or placebo). Serum samples drawn at 0, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, and 24 hours, following oral administration of a dose of levonorgestrel. Treatment between the two time periods was with St. John's Wort or placebo herb, beginning after the Time 1 (baseline) and continued for 5 weeks until Time 2. Estimates of levonorgestrel clearance were made using a two stage non-compartmental approach to determine individual and group parameters. | Area Under the Concentration versus Time curve for 0 to 24 hours after drug administration, between Days 9 and 12 of the menstrual cycle, done at Time 1 and at Time 2 |
| Number of Participants With Progesterone Levels Above 3.0 ng/ml at Time 1 (Baseline) and Time 2 (After Intervention With St John's Wort or Placebo). | Serum progesterone levels were drawn at the time of dosing with levonorgestrel and then at weekly intervals until menses occurred. This was done at Time 1 (baseline), and again at Time 2 (after 5 weeks of dosing with St. John's Wort or placebo). Possible ovulation was defined as a serum progesterone >3ng/ml within 2 weeks of Days 9-12 of the menstrual cycle. | Progesterone levels drawn at weekly intervals after dosing with levonorgestrel between Days 9 and 12 of the menstrual cycle, at each time point until menses |
| Clearance (L/hr) of Levonorgestrel Over 24 Hours for Each Dosage Group and Each Study Session. | Average and standard deviation for Clearance (L/hr) of Levonorgestrel study for each dosage group and each study session. | Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention) |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | Descriptive reporting of secondary outcomes of reproductive hormone levels (including FSH, E2, LH). Pharmacokinetic studies were done between Days 9-12 of the menstrual cycle at Time 1 (baseline, before any treatment with herb or placebo), and at Time 2 (intervention, after treatment with herb or placebo). Weekly means are reported for both time periods at week 0 (day of pharmacokinetic study), week 1 (one week after pharmacokinetic study) and week 2 (2 weeks after pharmacokinetic study). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Patricia A. Murphy, DrPH | College of Nursing, University of Utah | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Utah | Salt Lake City | Utah | 84112 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15914127 | Background | Murphy PA, Kern SE, Stanczyk FZ, Westhoff CL. Interaction of St. John's Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. Contraception. 2005 Jun;71(6):402-8. doi: 10.1016/j.contraception.2004.11.004. |
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No enrolled participants were excluded
Eligible participants were recruited via local advertising.
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| ID | Title | Description |
|---|---|---|
| FG000 | LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Group 1: one-time oral dose of levonorgestrel 1.5 mg at the first pharmacokinetic study, followed by placebo herb and a one-time oral dose of levonorgestrel 1.5 mg at the second pharmacokinetic study |
| FG001 | LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Group 2: One-time oral dose of levonorgestrel 1.5 mg at the first pharmacokinetic study, followed by St. John's Wort 300 mg orally three times per day, and a one-time oral dose of levonorgestrel 1.5 mg at the second pharmacokinetic study |
| FG002 | LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Group 3: A one-time oral dose of levonorgestrel 1.5 mg mg at the first pharmacokinetic study, followed by St. John's Wort 300 mg orally three times per day (900 mg total) and a one-time oral dose of levonorgestrel 2.25 mg at the second pharmacokinetic study |
| FG003 | LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Group 4: A one-time oral dose of levonorgestrel 1.5 mg at the first pharmacokinetic study, then St. John's Wort 300 mg orally five times per day (total 1500 mg daily) and a one-time oral dose of levonorgestrel 1.5 mg at the second pharmacokinetic study |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Time 1: First Intervention |
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| Time 2: Second Intervention |
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| ID | Title | Description |
|---|---|---|
| BG000 | LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Group 1: one-time oral dose of levonorgestrel 1.5 mg at the first pharmacokinetic study, followed by placebo herb and a one-time oral dose of levonorgestrel 1.5 mg at the second pharmacokinetic study |
| BG001 | LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Concentration Versus Time Curve for 0 to 24 Hours After Drug Administration, Done Between Days 9 and 12 of the Menstrual Cycle at Time 1 (Before) and Time 2 (During Treatment With St. John's Wort or Placebo) | Pharmacokinetic studies were done between Days 9-12 of the menstrual cycle at Time 1 (baseline, before any treatment with herb or placebo), and at Time 2 (intervention, after treatment with herb or placebo). Serum samples drawn at 0, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, and 24 hours, following oral administration of a dose of levonorgestrel. Treatment between the two time periods was with St. John's Wort or placebo herb, beginning after the Time 1 (baseline) and continued for 5 weeks until Time 2. Estimates of levonorgestrel clearance were made using a two stage non-compartmental approach to determine individual and group parameters. | Posted | Mean | Standard Deviation | ng*hr/mL | Area Under the Concentration versus Time curve for 0 to 24 hours after drug administration, between Days 9 and 12 of the menstrual cycle, done at Time 1 and at Time 2 |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg | Group 1: one-time oral dose of levonorgestrel 1.5 mg at the first pharmacokinetic study, followed by placebo herb and a one-time oral dose of levonorgestrel 1.5 mg at the second pharmacokinetic study |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Patricia Murphy, DrPH | University of Utah | 801-793-5729 | patricia.murphy@nurs.utah.edu |
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| ID | Term |
|---|---|
| C422326 | Hypericum extract LI 160 |
| D016912 | Levonorgestrel |
| ID | Term |
|---|---|
| D009644 | Norgestrel |
| D009652 | Norpregnenes |
| D009650 | Norpregnanes |
| D009654 | Norsteroids |
| D013256 |
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| St. John's Wort | Dietary Supplement | St. John's Wort (Hypericum perforatum) orally or 4-6 weeks |
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| Levonorgestrel | Drug | Levonorgestrel in a single oral dose |
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| Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention) |
| Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Descriptive reporting of secondary outcomes of reproductive hormone levels (including FSH, E2, LH). Pharmacokinetic studies were done between Days 9-12 of the menstrual cycle at Time 1 (baseline, before any treatment with herb or placebo), and at Time 2 (intervention, after treatment with herb or placebo). Weekly means are reported for both time periods at week 0 (day of pharmacokinetic study), week 1 (one week after pharmacokinetic study) and week 2 (2 weeks after pharmacokinetic study). | Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention) |
| Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | Descriptive reporting of secondary outcomes of reproductive hormone levels (including FSH, E2, LH). Pharmacokinetic studies were done between Days 9-12 of the menstrual cycle at Time 1 (baseline, before any treatment with herb or placebo), and at Time 2 (intervention, after treatment with herb or placebo). Weekly means are reported for both time periods at week 0 (day of pharmacokinetic study), week 1 (one week after pharmacokinetic study) and week 2 (2 weeks after pharmacokinetic study). | Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention) |
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| NOT COMPLETED |
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Group 2: One-time oral dose of levonorgestrel 1.5 mg at the first pharmacokinetic study, followed by St. John's Wort 300 mg orally three times per day, and a one-time oral dose of levonorgestrel 1.5 mg at the second pharmacokinetic study |
| BG002 | LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Group 3: A one-time oral dose of levonorgestrel 1.5 mg mg at the first pharmacokinetic study, followed by St. John's Wort 300 mg orally three times per day (900 mg total) and a one-time oral dose of levonorgestrel 2.25 mg at the second pharmacokinetic study |
| BG003 | LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Group 4: A one-time oral dose of levonorgestrel 1.5 mg at the first pharmacokinetic study, then St. John's Wort 300 mg orally five times per day (total 1500 mg daily) and a one-time oral dose of levonorgestrel 1.5 mg at the second pharmacokinetic study |
| BG004 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| LNG 1.5 mg Dose, Then Placebo Herb, LNG 1.5 mg |
Group 1: one-time oral dose of levonorgestrel 1.5 mg at the first pharmacokinetic study, followed by placebo herb and a one-time oral dose of levonorgestrel 1.5 mg at the second pharmacokinetic study |
| OG001 | LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Group 2: One-time oral dose of levonorgestrel 1.5 mg at the first pharmacokinetic study, followed by St. John's Wort 300 mg orally three times per day, and a one-time oral dose of levonorgestrel 1.5 mg at the second pharmacokinetic study |
| OG002 | LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Group 3: A one-time oral dose of levonorgestrel 1.5 mg mg at the first pharmacokinetic study, followed by St. John's Wort 300 mg orally three times per day (900 mg total) and a one-time oral dose of levonorgestrel 2.25 mg at the second pharmacokinetic study |
| OG003 | LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Group 4: A one-time oral dose of levonorgestrel 1.5 mg at the first pharmacokinetic study, then St. John's Wort 300 mg orally five times per day (total 1500 mg daily) and a one-time oral dose of levonorgestrel 1.5 mg at the second pharmacokinetic study |
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| Primary | Number of Participants With Progesterone Levels Above 3.0 ng/ml at Time 1 (Baseline) and Time 2 (After Intervention With St John's Wort or Placebo). | Serum progesterone levels were drawn at the time of dosing with levonorgestrel and then at weekly intervals until menses occurred. This was done at Time 1 (baseline), and again at Time 2 (after 5 weeks of dosing with St. John's Wort or placebo). Possible ovulation was defined as a serum progesterone >3ng/ml within 2 weeks of Days 9-12 of the menstrual cycle. | Posted | Number | Participants | Progesterone levels drawn at weekly intervals after dosing with levonorgestrel between Days 9 and 12 of the menstrual cycle, at each time point until menses |
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| Secondary | Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses | Descriptive reporting of secondary outcomes of reproductive hormone levels (including FSH, E2, LH). Pharmacokinetic studies were done between Days 9-12 of the menstrual cycle at Time 1 (baseline, before any treatment with herb or placebo), and at Time 2 (intervention, after treatment with herb or placebo). Weekly means are reported for both time periods at week 0 (day of pharmacokinetic study), week 1 (one week after pharmacokinetic study) and week 2 (2 weeks after pharmacokinetic study). | Posted | Mean | Standard Deviation | IU/mL | Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention) |
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| Primary | Clearance (L/hr) of Levonorgestrel Over 24 Hours for Each Dosage Group and Each Study Session. | Average and standard deviation for Clearance (L/hr) of Levonorgestrel study for each dosage group and each study session. | Posted | Mean | Standard Deviation | L/hr | Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention) |
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| Secondary | Mean Levels of Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses | Descriptive reporting of secondary outcomes of reproductive hormone levels (including FSH, E2, LH). Pharmacokinetic studies were done between Days 9-12 of the menstrual cycle at Time 1 (baseline, before any treatment with herb or placebo), and at Time 2 (intervention, after treatment with herb or placebo). Weekly means are reported for both time periods at week 0 (day of pharmacokinetic study), week 1 (one week after pharmacokinetic study) and week 2 (2 weeks after pharmacokinetic study). | Posted | Mean | Standard Deviation | pg/mL | Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention) |
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| Secondary | Mean Levels of Luteinizing Hormone, Drawn at Weekly Intervals Until Next Menses | Descriptive reporting of secondary outcomes of reproductive hormone levels (including FSH, E2, LH). Pharmacokinetic studies were done between Days 9-12 of the menstrual cycle at Time 1 (baseline, before any treatment with herb or placebo), and at Time 2 (intervention, after treatment with herb or placebo). Weekly means are reported for both time periods at week 0 (day of pharmacokinetic study), week 1 (one week after pharmacokinetic study) and week 2 (2 weeks after pharmacokinetic study). | Posted | Mean | Standard Deviation | IU/mL | Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention) |
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| 0 |
| 9 |
| 0 |
| 9 |
| EG001 | LNG 1.5 mg Dose, Then SJW 900 mg Day, LNG 1.5 mg | Group 2: One-time oral dose of levonorgestrel 1.5 mg at the first pharmacokinetic study, followed by St. John's Wort 300 mg orally three times per day, and a one-time oral dose of levonorgestrel 1.5 mg at the second pharmacokinetic study | 0 | 9 | 0 | 9 |
| EG002 | LNG 1.5 mg Dose, Then SJW 900 mg Daily, 2.25 mg LNG Dose | Group 3: A one-time oral dose of levonorgestrel 1.5 mg mg at the first pharmacokinetic study, followed by St. John's Wort 300 mg orally three times per day (900 mg total) and a one-time oral dose of levonorgestrel 2.25 mg at the second pharmacokinetic study | 0 | 9 | 0 | 9 |
| EG003 | LNG 1.5 mg Dose, Then SJW 1500 ng Day, 1.5 mg LNG | Group 4: A one-time oral dose of levonorgestrel 1.5 mg at the first pharmacokinetic study, then St. John's Wort 300 mg orally five times per day (total 1500 mg daily) and a one-time oral dose of levonorgestrel 1.5 mg at the second pharmacokinetic study | 0 | 9 | 0 | 9 |
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| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| Ovulation (Progesterone Levels >3.0 ng/ml) Time 2 |
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| FSH, IU/mL, Time 1, week 1 |
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| FSH, IU/mL, Time 1, week 2 |
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| FSH, IU/mL, Time 2, week 0 |
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| FSH, IU/mL, Time 2, week 1 |
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| FSH, IU/mL, Time 2, week 2 |
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| Clearance L/hr Time 2 |
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| Estradiol, pg/mL, Time 1, week 1 |
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| Estradiol, pg/mL,Time 1, week 2 |
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| Estradiol, pg/mL,Time 2, week 0 |
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| Estradiol, pg/mL,Time 2, week 1 |
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| Estradiol, pg/mL,Time 2, week 2 |
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| LH, IU/L, Time 1, week 1 |
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| LH, IU/L, Time 1, week 2 |
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| LH IU/L, Time 2, week 0 |
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| LH, IU/L, Time 2, week 1 |
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| LH, IU/L, Time 2, week 2 |
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