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

NCT ID: NCT05450978

Last Updated: 2025-04-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-07-20

Study Completion Date

2028-04-01

Brief Summary

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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

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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).

Conditions

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Epilepsy Pregnancy Related

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Lamotrigine (LTG)

Participants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with lamotrigine (LTG)

Lamotrigine

Intervention Type DRUG

Anti-seizure concentrations

Levetiracetam (LEV)

Participants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with Levetiracetam (LEV)

Levetiracetam

Intervention Type DRUG

Anti-seizure concentrations

Oxcarbazepine (OXC)

Participants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with with Oxcarbazepine (OXC)

Oxcarbazepine

Intervention Type DRUG

Anti-seizure concentrations

Interventions

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Lamotrigine

Anti-seizure concentrations

Intervention Type DRUG

Levetiracetam

Anti-seizure concentrations

Intervention Type DRUG

Oxcarbazepine

Anti-seizure concentrations

Intervention Type DRUG

Other Intervention Names

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Anti-seizure medication: Lamotrigine (LTG) Anti-seizure medication: Levetiracetam (LEV) Anti-seizure medication: Oxcarbazepine (OXC)

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

University of Pittsburgh

OTHER

Sponsor Role lead

Responsible Party

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Page B. Pennell, MD

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Page B Pennell, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Pittsburgh

Locations

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University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Tonge Ebai, PhD

Role: CONTACT

4126160730

Erica Kemp, PA

Role: CONTACT

Facility Contacts

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Tonge Ebai, PhD

Role: primary

412-592-4018

Erica Kemp, P.A.

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 33369356 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31886825 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35157004 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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R01HD105305

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY21090138

Identifier Type: -

Identifier Source: org_study_id

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