Women With Epilepsy: a Pilot Study of PK and PD Anti-epileptic Drug Effects in Levonorgestrel Intrauterine System Users

Study Overview
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Brief Summary
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The investigators will conduct a prospective, seven-month pilot study to explore pharmacokinetic (PK) and pharmacodynamic (PD) effects among women with epilepsy using the levonorgestrel intrauterine system (LNG IUS) for contraception. The investigators will enroll twenty women with well-controlled epilepsy maintained on stable anti-epileptic drugs (AED) therapy seeking the LNG IUS for contraception. The primary outcomes are AED levels and seizures before and after LNG IUS placement. Secondary outcomes include LNG levels, evidence of ovulation three weeks after insertion (serum progesterone >3ng/ml), bleeding and spotting, endometrial thickness, continuation, satisfaction and adverse events (removals, expulsions, side effects). The investigators will conduct a baseline month assessment, insertion visit, and follow-up visits at 21 days, three months and six months.

Detailed Description
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Study Procedures This pilot study consists of five study visits. Once preliminary eligibility is determined through a telephone screening interview, the first visit is scheduled. Visit 1 Enrollment/Baseline Review Eligibility Informed Consent Collect Baseline Information Vital Signs Pregnancy Test Complete Physical Exam including Pelvic exam, Chlamydia testing, and a Pap test if needed as per ASCCP (American Society for Colposcopy and Cervical Pathology) guidelines Receive diary to record any bleeding or spotting Receive condoms, if needed, for use until IUS insertion Sign release for contact of primary neurologist or epileptologist Study MD to contact participant's neurologist to notify of trial participation, and verify type and dose of AEDs Visit 2 Insertion/4-6 Weeks from Baseline Vital Signs Pregnancy Test Phlebotomy for hormone and AED levels Transvaginal ultrasound IUS Insertion Review and collect completed diary Receive new diary Visit 3/ Follow up 3 Weeks post IUS Insertion Vital Signs Phlebotomy for hormone and AED levels Transvaginal Ultrasound Review and collect completed diary Receive new diary Visit 4/Follow up 3 Months post IUS Insertion Vital Signs Phlebotomy for hormone and AED levels Transvaginal ultrasound Review and collect completed diary Receive new diary Acceptability Questionnaire Visit 5/ Exit 6 Months post IUS insertion Vital Signs Phlebotomy for hormone and AED levels Transvaginal Ultrasound Review and collect final completed diary Acceptability Questionnaire

Official Title
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Women With Epilepsy: a Pilot Study of Pharmacokinetic and Pharmacodynamic Anti-epileptic Drug Effects in Levonorgestrel Intrauterine System Users

Conditions
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Epilepsy, Contraception

Intervention / Treatment
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* Drug: levonorgestrel IUS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age18-45 years Regular menstrual cycle of length 21-35 days Willing to use IUS for contraception Willing to use non-hormonal contraception for one month before insertion Stable AED therapy for at least two months Well-controlled epilepsy (2 or fewer seizures, other than simple partial, per month) Working telephone English Speaking Exclusion Criteria: Current pregnancy or pregnancy in the previous two months Breastfeeding with amenorrhea Hepatic p450 enzyme inducing medications other than AEDs (griseofulvin, rifampin, St. John's Wort, bosentan) Depomedroxyprogesterone acetate within previous six months Congenital or acquired uterine anomaly, including myomas, that distort the uterine cavity Acute pelvic infection or a history pelvic infection without subsequent intrauterine pregnancy Postpartum endometritis or infected abortion in the last three months Genital bleeding of unknown etiology Untreated lower genital tract infection (cervical or vaginal) Acute liver disease or liver tumor, benign or malignant HIV infection or partner with HIV infection Increased susceptibility to pelvic infection A previously inserted intrauterine device (IUD) that has not been removed Hypersensitivity to any component of the LNG IUS Known or suspected carcinoma of the breast Current abnormal cervical cytology other than ASCUS or a history of abnormal cervical cytology other than ASCUS without appropriate follow-up demonstrating no evidence of disease History of genital tract malignancy Current use of anti-coagulants Current alcoholism or drug abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: levonorgestrel IUS<br>all women in the study underwent placement of the levonorgestrel IUS in an open-label fashion, outcomes were compared before and after placement. | Drug: levonorgestrel IUS<br>* placement of levonorgestrel intrauterine system<br>* Other names: Mirena;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants That Experienced Clinically Meaningful Change in Lamotrigine Level | The outcome measure is designed to examine whether participants will experience subtherapeutic or toxic serum trough level of lamotrigine after IUD insertion. | from baseline to 6 months after LNG IUS insertion | 
| Percent of Participants That Experienced Clinically Meaningful Change in Levetiracetam Level | The outcome measure is designed to examine whether participants will experience subtherapeutic or toxic serum trough level of levetiracetam after IUD insertion. | from baseline to 6 months after LNG IUS insertion | 
| Percent of Participants That Experienced Clinically Meaningful Change in Oxcarbazepine Level | The outcome measure is designed to examine whether participants will experience subtherapeutic or toxic serum trough level of oxcarbazepine after IUD insertion. | from baseline to 6 months after LNG IUS insertion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Seizure Frequency | Number of participants with increased, unchanged or decreased mean monthly seizure frequency. | baseline to 6 months | 
| Number of Participants Continuing With IUD | Women continuing the IUD for contraception at 6 months | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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epilepsy, contraception, drug interaction