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

• ClinicalTrials.gov Identifier: NCT02362373
• Recruitment Status: Completed
• First Posted: February 12, 2015
• Results First Posted: January 18, 2016
• Last Update Posted: January 18, 2016
• Sponsor: Columbia University
• Collaborator: Bayer
• Information provided by (Responsible Party): Anne Davis, Columbia University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Epilepsy; Contraception	Drug: levonorgestrel IUS	Phase 4

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: Women With Epilepsy: a Pilot Study of Pharmacokinetic and Pharmacodynamic Anti-epileptic Drug Effects in Levonorgestrel Intrauterine System Users
• Study Start Date: August 2011
• Actual Primary Completion Date: January 2014
• Actual Study Completion Date: January 2014

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: levonorgestrel IUS; placement of levonorgestrel intrauterine system; Other Name: Mirena

Outcome Measures

Primary Outcome Measures :

1. Percent of Participants That Experienced Clinically Meaningful Change in Lamotrigine Level [ Time Frame: 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.
2. Percent of Participants That Experienced Clinically Meaningful Change in Levetiracetam Level [ Time Frame: 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.
3. Percent of Participants That Experienced Clinically Meaningful Change in Oxcarbazepine Level [ Time Frame: 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 Outcome Measures :

1. Change in Seizure Frequency [ Time Frame: baseline to 6 months ]
   Number of participants with increased, unchanged or decreased mean monthly seizure frequency.
2. Number of Participants Continuing With IUD [ Time Frame: 6 months ]
   Women continuing the IUD for contraception at 6 months

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, New York

Columbia University

New York, New York, United States, 10032

Sponsors and Collaborators

Columbia University

Bayer

Investigators

• Principal Investigator: Anne Davis, MD; Columbia University

More Information

• Responsible Party: Anne Davis, Associate Professor of Clinical Obstetrics and Gynecology, Columbia University
• ClinicalTrials.gov Identifier: NCT02362373 History of Changes
• Other Study ID Numbers: AAAI0750
• First Posted: February 12, 2015
• Results First Posted: January 18, 2016
• Last Update Posted: January 18, 2016
• Last Verified: December 2015

Keywords provided by Anne Davis, Columbia University:

epilepsy; contraception; drug interaction

Additional relevant MeSH terms:

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Levonorgestrel; Anticonvulsants; Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Contraceptives, Oral, Synthetic; Contraceptives, Oral