- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00131885
Effects of St. John's Wort on the Oral Contraceptive Hormone Levonorgestrel
Effects of St. John's Wort on Levonorgestrel
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Utah
-
Salt Lake City, Utah, United States, 84112
- University of Utah
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Body mass index (BMI) between 20 and 25
- Regular menstrual cycles for at least 3 months prior to study entry
Exclusion Criteria:
- Current use of foods, herbs, vitamins, over-the-counter supplements, or any medications that could alter pharmacokinetics of other drugs
- Medical contraindications to the use of contraceptives
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Levonorgestrel 1.5 with Placebo Herb
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
|
Placebo herb three times daily (ground cellulose) for 4-6 weeks
Levonorgestrel in a single oral dose
|
Active Comparator: Levonorgestrel 1.5 with SJW 900 mg
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
|
Levonorgestrel in a single oral dose
St. John's Wort (Hypericum perforatum) orally or 4-6 weeks
|
Active Comparator: Levonorgestrel 2.25 with SJW 900 mg
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
|
Levonorgestrel in a single oral dose
St. John's Wort (Hypericum perforatum) orally or 4-6 weeks
|
Active Comparator: Levonorgestrel 1.5 with SJW 1500 mg
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
|
Levonorgestrel in a single oral dose
St. John's Wort (Hypericum perforatum) orally or 4-6 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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)
Time Frame: 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
|
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).
Time Frame: 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
|
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.
Time Frame: Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
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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)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean Levels of Follicle-stimulating Hormone Drawn at Weekly Intervals Until Next Menses
Time Frame: Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
|
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 Estradiol-17b (E2) Drawn at Weekly Intervals Until Next Menses
Time Frame: Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
|
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
Time Frame: Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
|
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)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Patricia A. Murphy, DrPH, College of Nursing, University of Utah
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 13430
- R21AT002297 (U.S. NIH Grant/Contract)
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