Effects of St. John's Wort on the Oral Contraceptive Hormone Levonorgestrel (R21 AT002297)

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
University of Utah
ClinicalTrials.gov Identifier:
NCT00131885
First received: August 17, 2005
Last updated: August 10, 2011
Last verified: August 2011
  Purpose

This study will determine the effects of St. John's wort, a common herbal remedy, on metabolism of the female contraceptive hormone levonorgestrel.


Condition Intervention Phase
Contraception
Dietary Supplement: Placebo Control (Placebo Herb)
Dietary Supplement: St. John's Wort
Drug: Levonorgestrel
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Effects of St. John's Wort on Levonorgestrel

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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).

    12 serum samples drawn from 0 to 24 hours of 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 ] [ Designated as safety issue: No ]

    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: Clearance at 24 hours from dosing ] [ Designated as safety issue: No ]
    Average and standard deviation for Clearance (L/hr) of Levonorgestrel study for each dosage group and each study session.


Secondary Outcome Measures:
  • Mean Levels of Follicle-stimulating Hormone, Estradiol-17b (E2), Luteinizing Hormone, Inhibin, and Glycodelin Drawn at Weekly Intervals Until Next Menses [ Time Frame: Weekly mean levels of reproductive hormones ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: August 2005
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Dietary Supplement: Placebo Control (Placebo Herb)
Placebo herb three times daily (ground cellulose) for 4-6 weeks
Drug: Levonorgestrel
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
Dietary Supplement: St. John's Wort
St. John's Wort (Hypericum perforatum) orally or 4-6 weeks
Drug: Levonorgestrel
Levonorgestrel in a single oral dose
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
Dietary Supplement: St. John's Wort
St. John's Wort (Hypericum perforatum) orally or 4-6 weeks
Drug: Levonorgestrel
Levonorgestrel in a single oral dose
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
Dietary Supplement: St. John's Wort
St. John's Wort (Hypericum perforatum) orally or 4-6 weeks
Drug: Levonorgestrel
Levonorgestrel in a single oral dose

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.

  Eligibility

Ages Eligible for Study:   18 Years to 30 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00131885

Locations
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
University of Utah
Investigators
Principal Investigator: Patricia A. Murphy, DrPH College of Nursing, University of Utah
  More Information

Publications:
Responsible Party: Patricia Murphy, DrPH, University of Utah
ClinicalTrials.gov Identifier: NCT00131885     History of Changes
Other Study ID Numbers: 13430, R21AT002297
Study First Received: August 17, 2005
Results First Received: March 21, 2010
Last Updated: August 10, 2011
Health Authority: United States: Federal Government

Keywords provided by University of Utah:
Menstruation
Complementary Therapies
Pharmacokinetics
Hypericum
St. John's wort
Levonorgestrel
Women

Additional relevant MeSH terms:
Levonorgestrel
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptives, Oral, Synthetic
Contraceptives, Oral

ClinicalTrials.gov processed this record on September 16, 2014