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Effects of St. John's Wort on the Oral Contraceptive Hormone Levonorgestrel

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ClinicalTrials.gov Identifier: NCT00131885
Recruitment Status : Completed
First Posted : August 19, 2005
Results First Posted : June 9, 2010
Last Update Posted : August 11, 2015
Sponsor:
Collaborator:
National Center for Complementary and Integrative Health (NCCIH)
Information provided by (Responsible Party):
Patricia Murphy, University of Utah

Tracking Information
First Submitted Date  ICMJE August 17, 2005
First Posted Date  ICMJE August 19, 2005
Results First Submitted Date  ICMJE March 21, 2010
Results First Posted Date  ICMJE June 9, 2010
Last Update Posted Date August 11, 2015
Study Start Date  ICMJE August 2005
Actual Primary Completion Date May 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 15, 2015)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 17, 2005)
  • Pharmacokinetic studies between Days 9 and 12 of the menstrual cycle before and during treatment with St. John's wort or placebo
  • ovulation, defined as progesterone levels 3.0 ng/ml at weekly intervals after dosing until menses
Change History Complete list of historical versions of study NCT00131885 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2015)
  • 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).
  • 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).
  • 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: August 17, 2005)
Mean Levels of Follicle-stimulating Hormone, Estradiol-17b (E2), Luteinizing Hormone, Inhibin, and Glycodelin Drawn at Weekly Intervals Until Next Menses
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of St. John's Wort on the Oral Contraceptive Hormone Levonorgestrel
Official Title  ICMJE Effects of St. John's Wort on Levonorgestrel
Brief Summary 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Contraception
Intervention  ICMJE
  • Dietary Supplement: Placebo Control (Placebo Herb)
    Placebo herb three times daily (ground cellulose) for 4-6 weeks
  • 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
Study Arms  ICMJE
  • 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
    Interventions:
    • Dietary Supplement: Placebo Control (Placebo Herb)
    • Drug: Levonorgestrel
  • 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
    Interventions:
    • Dietary Supplement: St. John's Wort
    • Drug: Levonorgestrel
  • 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
    Interventions:
    • Dietary Supplement: St. John's Wort
    • Drug: Levonorgestrel
  • 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
    Interventions:
    • Dietary Supplement: St. John's Wort
    • Drug: Levonorgestrel
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 17, 2005)
36
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 2008
Actual Primary Completion Date May 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 30 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00131885
Other Study ID Numbers  ICMJE 13430
R21AT002297 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Patricia Murphy, University of Utah
Study Sponsor  ICMJE University of Utah
Collaborators  ICMJE National Center for Complementary and Integrative Health (NCCIH)
Investigators  ICMJE
Principal Investigator: Patricia A. Murphy, DrPH College of Nursing, University of Utah
PRS Account University of Utah
Verification Date July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP