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

Phase 4
Completed
Conditions
Epilepsy
Contraception
Interventions
Registration Number
NCT02362373
Lead Sponsor
Columbia University
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

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
20
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
Read More
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
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
levonorgestrel IUSlevonorgestrel IUSall women in the study underwent placement of the levonorgestrel IUS in an open-label fashion, outcomes were compared before and after placement.
Primary Outcome Measures
NameTimeMethod
Percent of Participants That Experienced Clinically Meaningful Change in Lamotrigine Levelfrom baseline to 6 months after LNG IUS insertion

The outcome measure is designed to examine whether participants will experience subtherapeutic or toxic serum trough level of lamotrigine after IUD insertion.

Percent of Participants That Experienced Clinically Meaningful Change in Levetiracetam Levelfrom baseline to 6 months after LNG IUS insertion

The outcome measure is designed to examine whether participants will experience subtherapeutic or toxic serum trough level of levetiracetam after IUD insertion.

Percent of Participants That Experienced Clinically Meaningful Change in Oxcarbazepine Levelfrom baseline to 6 months after LNG IUS insertion

The outcome measure is designed to examine whether participants will experience subtherapeutic or toxic serum trough level of oxcarbazepine after IUD insertion.

Secondary Outcome Measures
NameTimeMethod
Change in Seizure Frequencybaseline to 6 months

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

Number of Participants Continuing With IUD6 months

Women continuing the IUD for contraception at 6 months

Trial Locations

Locations (1)

Columbia University

🇺🇸

New York, New York, United States

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