Epilepsy, Contraception
Conditions
Keywords
epilepsy, contraception, drug interaction
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
Interventions
placement of levonorgestrel intrauterine system
Sponsors
Bayer
Columbia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants That Experienced Clinically Meaningful Change in Lamotrigine Level | from 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 Level | from 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 Level | from 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Seizure Frequency | baseline to 6 months | Number of participants with increased, unchanged or decreased mean monthly seizure frequency. |
| Number of Participants Continuing With IUD | 6 months | Women continuing the IUD for contraception at 6 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Levonorgestrel IUS all women in the study underwent placement of the levonorgestrel IUS in an open-label fashion, outcomes were compared before and after placement.
levonorgestrel IUS: placement of levonorgestrel intrauterine system | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Levonorgestrel IUS |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age, Continuous | 28 years STANDARD_DEVIATION 6.2 |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
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
Population: 13 out of 20 participants received lamotrigine while on IUD.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Women With Epilepsy Receiving the LNG IUS | Percent of Participants That Experienced Clinically Meaningful Change in Lamotrigine Level | 0 percentage of participants |
Primary
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
Population: 5 out of 20 participants received levetiracetam while on IUD.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Women With Epilepsy Receiving the LNG IUS | Percent of Participants That Experienced Clinically Meaningful Change in Levetiracetam Level | 0 percentage of participants |
Primary
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
Population: 3 out of 20 participants received oxcarbazepine while on IUD.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Women With Epilepsy Receiving the LNG IUS | Percent of Participants That Experienced Clinically Meaningful Change in Oxcarbazepine Level | 0 percentage of participants |
Secondary
Change in Seizure Frequency
Number of participants with increased, unchanged or decreased mean monthly seizure frequency.
Time frame: baseline to 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Women With Epilepsy Receiving the LNG IUS | Change in Seizure Frequency | Seizure control unchanged | 13 participants |
| Women With Epilepsy Receiving the LNG IUS | Change in Seizure Frequency | Seizure control decreased | 3 participants |
| Women With Epilepsy Receiving the LNG IUS | Change in Seizure Frequency | Seizure control improved | 4 participants |
Secondary
Number of Participants Continuing With IUD
Women continuing the IUD for contraception at 6 months
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Women With Epilepsy Receiving the LNG IUS | Number of Participants Continuing With IUD | 20 participants |