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

Columbia University

Status and phase: Completed; Phase 4

Conditions: Epilepsy; Contraception

Treatments: Drug: levonorgestrel IUS

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02362373

AAAI0750

Details and patient eligibility

About

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.

Full description

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

Enrollment: 20 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

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

Trial design

20 participants in 1 patient group

levonorgestrel IUS

Other group

Description:

all women in the study underwent placement of the levonorgestrel IUS in an open-label fashion, outcomes were compared before and after placement.

Treatment:

Drug: levonorgestrel IUS