ContraceptionPhase 4NCT00131885
Effects of St. John's Wort on the Oral Contraceptive Hormone Levonorgestrel
A Phase 4 study testing St. John's Wort and Levonorgestrel in people with Contraception, run by University of Utah at 1 site in United States.
Trial summary
This study will determine the effects of St. John's wort, a common herbal remedy, on metabolism of the female contraceptive hormone levonorgestrel. Read more about this study
- Who is it for?
- Ages 18 to 30 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Contraception
- What is being tested?
- St. John's Wort and Levonorgestrel
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2005to May 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 30 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Body mass index (BMI) between 20 and 25
- Regular menstrual cycles for at least 3 months prior to study entry
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of St. John's Wort on Levonorgestrel
This study will determine the effects of St. John's wort, a common herbal remedy, on metabolism of the female contraceptive hormone levonorgestrel.
Read the 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.
- Conditions
- Contraception
- Being tested
- Placebo Control (Placebo Herb), St. John's Wort, Levonorgestrel
- Keywords
- Menstruation, Complementary Therapies, Pharmacokinetics, Hypericum, St. John's wort, Levonorgestrel, Women
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo Control (Placebo Herb)Dietary supplement
Placebo herb three times daily (ground cellulose) for 4-6 weeks
St. John's WortDietary supplement
St. John's Wort (Hypericum perforatum) orally or 4-6 weeks
LevonorgestrelDrug
Levonorgestrel in a single oral dose
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Dietary Supplement: Placebo Control (Placebo Herb); Drug: Levonorgestrel |
| 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 Receives: Dietary Supplement: St. John's Wort; Drug: Levonorgestrel |
| 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 Receives: Dietary Supplement: St. John's Wort; Drug: Levonorgestrel |
| 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 Receives: Dietary Supplement: St. John's Wort; Drug: Levonorgestrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
Secondary outcomes (3)
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).
Measured: 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).
Measured: 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).
Measured: Time Frame: Time 1 (pre-intervention baseline) and Time 2 (following a 6 week intervention)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2005 (estimated)
- Study startAug 2005
- Primary completionMay 2008
- Study completionMay 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ContraceptionStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH)
- Responsible party
- Principal investigator, Patricia Murphy, University of Utah
- Investigators
- Patricia A. Murphy, DrPH, Principal investigator, College of Nursing, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00131885
- Sponsor's protocol ID
- 13430
- Other IDs
- R21AT002297
- Status last verified
- Nov 2023
- First submitted
- 17 Aug 2005
- Last updated
- 13 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 15914127
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of St. John's Wort on Levonorgestrel
- ClinicalTrials.gov ID
- NCT00131885
- Acronym / sponsor ID
- 13430
- Conditions
- Contraception
- Keywords
- Menstruation, Complementary Therapies, Pharmacokinetics, Hypericum, St. John's wort, Levonorgestrel, Women
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH)
- Study start
- Aug 2005
- Primary completion
- May 2008 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 19 Aug 2005 (estimated)
- Results
- Posted 9 Jun 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will determine the effects of St. John's wort, a common herbal remedy, on metabolism of the female contraceptive hormone levonorgestrel.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Levonorgestrel 1.5 with Placebo Herb | Placebo comparator | Dietary Supplement: Placebo Control (Placebo Herb), Drug: LevonorgestrelThis 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 |
| Levonorgestrel 1.5 with SJW 900 mg | Active comparator | Dietary Supplement: St. John's Wort, Drug: LevonorgestrelThis 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 2.25 with SJW 900 mg | Active comparator | Dietary Supplement: St. John's Wort, Drug: LevonorgestrelThis 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 1.5 with SJW 1500 mg | Active comparator | Dietary Supplement: St. John's Wort, Drug: LevonorgestrelThis 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 |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Body mass index (BMI) between 20 and 25
- Regular menstrual cycles for at least 3 months prior to study entry
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo Control (Placebo Herb)Placebo herb three times daily (ground cellulose) for 4-6 weeks | Dietary supplement | Levonorgestrel 1.5 with Placebo Herb |
| St. John's WortSt. John's Wort (Hypericum perforatum) orally or 4-6 weeks | Dietary supplement | Levonorgestrel 1.5 with SJW 1500 mg, Levonorgestrel 1.5 with SJW 900 mg, Levonorgestrel 2.25 with SJW 900 mg |
| LevonorgestrelLevonorgestrel in a single oral dose | Drug | Levonorgestrel 1.5 with Placebo Herb, Levonorgestrel 1.5 with SJW 1500 mg, Levonorgestrel 1.5 with SJW 900 mg, Levonorgestrel 2.25 with SJW 900 mg |
Primary outcome
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.
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.
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)
Average and standard deviation for Clearance (L/hr) of Levonorgestrel study for each dosage group and each study session.
3 secondary outcomes
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)
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15914127Murphy 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patricia A. Murphy, DrPH principal investigator
College of Nursing, University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing St. John's Wort and Levonorgestrel in people with Contraception, run by University of Utah at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00131885, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2023.