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

Columbia University20 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 45 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age18-45 years 2. Regular menstrual cycle of length 21-35 days 3. Willing to use IUS for contraception 4. Willing to use non-hormonal contraception for one month before insertion 5. Stable AED therapy for at least two months 6. Well-controlled epilepsy (2 or fewer seizures, other than simple partial, per month) 7. Working telephone 8. English Speaking Exclusion Criteria: 1. Current pregnancy or pregnancy in the previous two months 2. Breastfeeding with amenorrhea 3. Hepatic p450 enzyme inducing medications other than AEDs (griseofulvin, rifampin, St. John's Wort, bosentan) 4. Depomedroxyprogesterone acetate within previous six months 5. Congenital or acquired uterine anomaly, including myomas, that distort the uterine cavity 6. Acute pelvic infection or a history pelvic infection without subsequent intrauterine pregnancy 7. Postpartum endometritis or infected abortion in the last three months 8. Genital bleeding of unknown etiology 9. Untreated lower genital tract infection (cervical or vaginal) 10. Acute liver disease or liver tumor, benign or malignant 11. HIV infection or partner with HIV infection 12. Increased susceptibility to pelvic infection 13. A previously inserted intrauterine device (IUD) that has not been removed 14. Hypersensitivity to any component of the LNG IUS 15. Known or suspected carcinoma of the breast 16. 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 17. History of genital tract malignancy 18. Current use of anti-coagulants 19. Current alcoholism or drug abuse

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: from baseline to 6 months after LNG IUS insertion

Secondary Outcomes

Change in Seizure Frequency

Number of participants with increased, unchanged or decreased mean monthly seizure frequency.

Time frame: baseline to 6 months

Number of Participants Continuing With IUD

Women continuing the IUD for contraception at 6 months

Time frame: 6 months

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes