Physiological-based Pharmacokinetics Approach to Medication Exposure During Pregnancy and Breastfeeding

Study Overview
=================
Brief Summary
-----------------
This project focuses on anti-seizure medication (ASM) clearance and physiological factors determining blood concentrations in pregnant adult women with epilepsy and amounts of exposure to their unborn children and nursing infants.

Detailed Description
-----------------
The goal of this study is to develop modeling of pharmacokinetic changes for Antiseizure medications (ASMs), lamotrigine (LTG), and levetiracetam (LEV) during pregnancy and postpartum that can be used to: Adjust doses in practice without obtaining frequent visits to the lab for therapeutic drug monitoring. Predict exposure of LTG and LEV in mothers and their infants in order to maintain the individualized target concentrations, thus protecting mothers from seizure worsening and minimizing fetal toxicity. Hypotheses: Drug concentrations obtained in preconception and early pregnancy predict clearance changes throughout the remainder of pregnancy for individual pregnant women with epilepsy (WWE). Validated model allows the prediction of drug concentration changes at all stages throughout and after pregnancy, which will more accurately predict increased seizures and medication side effects.

Official Title
-----------------
Physiological-based Pharmacokinetics Approach to Determine the Extent of Drug Exposure of Antiseizure Medications During Pregnancy and Breastfeeding

Conditions
-----------------
Epilepsy, Pregnancy Related

Intervention / Treatment
-----------------
* Drug: Lamotrigine
* Drug: Levetiracetam


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women planning pregnancy within the next 6 months. Women currently being treated with lamotrigine (LTG) or levetiracetam (LEV) for a diagnosis of epilepsy Exclusion Criteria: History of psychogenic non-epileptic spells History of other major medical illnesses including renal or hepatic disease, progressive cerebral disease, Inability to maintain a seizure and medication daily diary Present or recent history of drug or alcohol abuse, or the use of any concomitant medications that interact with the ASM they are taking (lamotrigine or levetiracetam).

Ages Eligible for Study
-----------------
Minimum Age: 14 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lamotrigine (LTG)<br>Participants will include women with epilepsy planning pregnancy within the next 6 months and treated with lamotrigine (LTG) | Drug: Lamotrigine<br>* Anti-seizure concentrations<br>* Other names: Anti-seizure medication: Lamotrigine (LTG);|
| Levetiracetam (LEV)<br>Participants will include women with epilepsy planning pregnancy within the next 6 months and treated with Levetiracetam (LEV) | Drug: Levetiracetam<br>* Anti-seizure concentrations<br>* Other names: Anti-seizure medication: Levetiracetam (LEV);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-Seizure Medication (ASM) Clearance | ASM Clearance will be calculated from measurements of lamotrigine and levetiracetam blood concentrations, serum creatinine and 24-hour urine collection (for levetiracetam), glucuronidated metabolite (for lamotrigine), steroid hormones, medication formulation and doses, time since recent doses, and participant weight. | Through study completion, an average of 18 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seizure Frequency | Participants will keep a daily seizure diary throughout their participation in the study. The diary will be reviewed at each study visit. | Through study completion, an average of 18 months. | 
| Anti-seizure Medication (ASM) Side Effects | An ASM Side Effect Questionnaire will be administered and a neurologic examination will be performed at each study visit. | Through study completion, an average of 18 months | 
| Placental passage of Anti-Seizure Medications (ASM) | Maternal blood will be drawn and umbilical cord blood will be collected, for measurements of ASM concentrations for lamotrigine and levetiracetam. | Through study completion, an average of 18 months |