Clinical trial NCT02362373: Women With Epilepsy: a Pilot Study of PK and PD Anti-epileptic Drug Effects in Levonorgestrel Intrauterine System Users
Official title: Women With Epilepsy: a Pilot Study of Pharmacokinetic and Pharmacodynamic Anti-epileptic Drug Effects in Levonorgestrel Intrauterine System Users
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Epilepsy
Contraception
Keywords: epilepsy
contraception
drug interaction
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2015-02-12
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Percent of Participants That Experienced Clinically Meaningful Change in Lamotrigine Level
timeFrame: from baseline to 6 months after LNG IUS insertion
measure: Percent of Participants That Experienced Clinically Meaningful Change in Levetiracetam Level
timeFrame: from baseline to 6 months after LNG IUS insertion
measure: Percent of Participants That Experienced Clinically Meaningful Change in Oxcarbazepine Level
timeFrame: from baseline to 6 months after LNG IUS insertion
Secondary outcomes:
measure: Change in Seizure Frequency
timeFrame: baseline to 6 months
measure: Number of Participants Continuing With IUD
timeFrame: 6 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University
state: New York
Study officials:
affiliation: Columbia University
name: Anne Davis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vieira CS, Pack A, Roberts K, Davis AR. A pilot study of levonorgestrel concentrations and bleeding patterns in women with epilepsy using a levonorgestrel IUD and treated with antiepileptic drugs. Contraception. 2019 Apr;99(4):251-255. doi: 10.1016/j.contraception.2018.11.018. Epub 2018 Dec 4.