Clinical trial NCT05450978: Physiological-based Pharmacokinetics Approach to Medication Exposure During Pregnancy and Breastfeeding
Official title: Physiological-based Pharmacokinetics Approach to Determine the Extent of Drug Exposure of Antiseizure Medications During Pregnancy and Breastfeeding
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Epilepsy
Pregnancy Related
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2022-07-11
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants to be mainly recruited from Neurology and OBGYN clinics.

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:

1. Adjust doses in practice without obtaining frequent visits to the lab for therapeutic drug monitoring.
2. Predict exposure of ASMs in mothers and their infants in order to maintain the individualized target concentrations, thus protecting mothers from seizure worsening and minimizing fetal toxicity.

Hypotheses:

1. Drug concentrations obtained in preconception and early pregnancy predict clearance changes throughout the remainder of pregnancy for individual pregnant women with epilepsy.
2. 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.

Additionally, pilot data will be obtained for oxcarbazepine (OXC) in a small number of participants and contribute to data for ASMs that undergo glucuronidation (LTG).

Eligibility criteria: Inclusion Criteria:

* Woman with epilepsy between the ages of 18-45 planning pregnancy or in the early first trimester of pregnancy.
* Women with epilepsy ability to maintain a daily medical diary
* Women with epilepsy ability to answer side effect questionnaires
* Women with epilepsy currently being treated with lamotrigine (LTG) or levetiracetam (LEV) or oxcarbazepine (OXC)

Exclusion Criteria:

* Women with epilepsy having history of functional seizures.
* Women with epilepsy history of other major medical illnesses including renal or hepatic disease, progressive cerebral disease,
* Women with epilepsy who have inability to maintain a seizure and medication daily diary
* Women with epilepsy with 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, levetiracetam, oxcarbazepine).

Primary outcomes:
measure: Anti-Seizure Medication (ASM) Clearance
timeFrame: Through study completion, an average of 18 months.
Secondary outcomes:
measure: Seizure Frequency
timeFrame: Through study completion, an average of 18 months.
measure: Anti-seizure Medication (ASM) Side Effects
timeFrame: Through study completion, an average of 18 months
measure: Placental passage of Anti-Seizure Medications (ASM)
timeFrame: Through study completion, an average of 18 months
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: The University of Pittsburgh
name: Page B Pennell, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pennell PB, French JA, May RC, Gerard E, Kalayjian L, Penovich P, Gedzelman E, Cavitt J, Hwang S, Pack AM, Sam M, Miller JW, Wilson SH, Brown C, Birnbaum AK, Meador KJ; MONEAD Study Group. Changes in Seizure Frequency and Antiepileptic Therapy during Pregnancy. N Engl J Med. 2020 Dec 24;383(26):2547-2556. doi: 10.1056/NEJMoa2008663.
citation: Birnbaum AK, Meador KJ, Karanam A, Brown C, May RC, Gerard EE, Gedzelman ER, Penovich PE, Kalayjian LA, Cavitt J, Pack AM, Miller JW, Stowe ZN, Pennell PB; MONEAD Investigator Group. Antiepileptic Drug Exposure in Infants of Breastfeeding Mothers With Epilepsy. JAMA Neurol. 2020 Apr 1;77(4):441-450. doi: 10.1001/jamaneurol.2019.4443.
citation: Pennell PB, Karanam A, Meador KJ, Gerard E, Kalayjian L, Penovich P, Matthews A, McElrath TM, Birnbaum AK; MONEAD Study Group. Antiseizure Medication Concentrations During Pregnancy: Results From the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) Study. JAMA Neurol. 2022 Apr 1;79(4):370-379. doi: 10.1001/jamaneurol.2021.5487.