EpilepsyPBPKNCT05450978
Physiological-based Pharmacokinetics Approach to Medication Exposure During Pregnancy and Breastfeeding
An observational study of Epilepsy and Pregnancy Related, run by University of Pittsburgh at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Epilepsy, Pregnancy Related
- What is being tested?
- Lamotrigine, Levetiracetam and Oxcarbazepine
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jul 2022to 1 Apr 2028
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Study population: Participants to be mainly recruited from Neurology and OBGYN clinics.
Who may be able to join
- 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)
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Erica Kemp, PA contact
United States1 site, 1 recruiting
- Recruiting
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Tonge Ebai, PhD, 412-592-4018, ebait@upmc.edu
Erica Kemp, P.A., kempe2@upmc.edu
About this study
Official title: Physiological-based Pharmacokinetics Approach to Determine the Extent of Drug Exposure of Antiseizure Medications During Pregnancy and Breastfeeding
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.
Read the 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 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:
- Drug concentrations obtained in preconception and early pregnancy predict clearance changes throughout the remainder of pregnancy for individual pregnant women with epilepsy.
- 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
- Epilepsy, Pregnancy Related
- Being tested
- Lamotrigine, Levetiracetam, Oxcarbazepine
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LamotrigineDrug
Also called Anti-seizure medication: Lamotrigine (LTG)
Anti-seizure concentrations
LevetiracetamDrug
Also called Anti-seizure medication: Levetiracetam (LEV)
Anti-seizure concentrations
OxcarbazepineDrug
Also called Anti-seizure medication: Oxcarbazepine (OXC)
Anti-seizure concentrations
| Study group | Role | What they receive |
|---|---|---|
| Lamotrigine (LTG) | Participants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with lamotrigine (LTG) Receives: Drug: Lamotrigine | |
| Levetiracetam (LEV) | Participants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with Levetiracetam (LEV) Receives: Drug: Levetiracetam | |
| Oxcarbazepine (OXC) | Participants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with with Oxcarbazepine (OXC) Receives: Drug: Oxcarbazepine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anti-Seizure Medication (ASM) Clearance
ASM Clearance will be calculated from measurements of lamotrigine, oxcarbazepine, 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.
Measured: Through study completion, an average of 18 months.
Secondary outcomes (3)
Seizure Frequency
Participants will keep a daily seizure diary throughout their participation in the study. The diary will be reviewed at each study visit.
Measured: 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.
Measured: 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, oxcarbazepine, and levetiracetam.
Measured: Through study completion, an average of 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2022
- Study start20 Jul 2022
- Primary completion1 Apr 2027 (estimated)
- Study completion1 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Page B. Pennell, MD, University of Pittsburgh
- Investigators
- Page B Pennell, MD, Principal investigator, The University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05450978
- Sponsor's protocol ID
- STUDY21090138
- Other IDs
- R01HD105305
- Acronym
- PBPK
- Status last verified
- May 2026
- First submitted
- 22 Jun 2022
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: We will adhere to the NIH Grants Policy Statement on Sharing of Biomedical Research Resources, including the "Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources: Final Notice." The results of the studies proposed here will be shared with the scientific community on a regular basis through presentations at scientific meetings and peer-reviewed publications in appropriate scientific journals. Any material resources developed as a result of this grant will be made available to other investigators once a Material Transfer Agreement has been signed between the University of Pittsburgh, University of Minnesota and the requesting investigator's institution.
Publications
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.
PubMed 33369356Birnbaum 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.
PubMed 31886825Pennell 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.
PubMed 35157004
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physiological-based Pharmacokinetics Approach to Determine the Extent of Drug Exposure of Antiseizure Medications During Pregnancy and Breastfeeding
- ClinicalTrials.gov ID
- NCT05450978
- Acronym / sponsor ID
- PBPK / STUDY21090138
- Conditions
- Epilepsy, Pregnancy Related
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 20 Jul 2022 (actual)
- Primary completion
- 1 Apr 2027 (estimated)
- Study completion
- 1 Apr 2028 (estimated)
- First posted
- 11 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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:
- Drug concentrations obtained in preconception and early pregnancy predict clearance changes throughout the remainder of pregnancy for individual pregnant women with epilepsy.
- 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).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Lamotrigine (LTG) | – | Drug: LamotrigineParticipants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with lamotrigine (LTG) |
| Levetiracetam (LEV) | – | Drug: LevetiracetamParticipants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with Levetiracetam (LEV) |
| Oxcarbazepine (OXC) | – | Drug: OxcarbazepineParticipants will include women with epilepsy planning pregnancy or in the early first trimester of pregnancy and treated with with Oxcarbazepine (OXC) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Participants to be mainly recruited from Neurology and OBGYN clinics.
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (4 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LamotrigineAlso: Anti-seizure medication: Lamotrigine (LTG)Anti-seizure concentrations | Drug | Lamotrigine (LTG) |
| LevetiracetamAlso: Anti-seizure medication: Levetiracetam (LEV)Anti-seizure concentrations | Drug | Levetiracetam (LEV) |
| OxcarbazepineAlso: Anti-seizure medication: Oxcarbazepine (OXC)Anti-seizure concentrations | Drug | Oxcarbazepine (OXC) |
Primary outcome
Anti-Seizure Medication (ASM) Clearance
Time frame: Through study completion, an average of 18 months.
ASM Clearance will be calculated from measurements of lamotrigine, oxcarbazepine, 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.
3 secondary outcomes
Seizure Frequency
Time frame: Through study completion, an average of 18 months.
Anti-seizure Medication (ASM) Side Effects
Time frame: Through study completion, an average of 18 months
Placental passage of Anti-Seizure Medications (ASM)
Time frame: Through study completion, an average of 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Background: PubMed 33369356Pennell 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.
- Background: PubMed 31886825Birnbaum 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.
- Background: PubMed 35157004Pennell 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.
- Individual participant dataSharing planned: Undecided. We will adhere to the NIH Grants Policy Statement on Sharing of Biomedical Research Resources, including the "Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources: Final Notice." The results of the studies proposed here will be shared with the scientific community on a regular basis through presentations at scientific meetings and peer-reviewed publications in appropriate scientific journals. Any material resources developed as a result of this grant will be made available to other investigators once a Material Transfer Agreement has been signed between the University of Pittsburgh, University of Minnesota and the requesting investigator's institution.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Erica Kemp, PA contact
Page B Pennell, MD principal investigator
The University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Epilepsy and Pregnancy Related, run by University of Pittsburgh at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tonge Ebai, PhD (4126160730, ebait@upmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Anti-Seizure Medication (ASM) Clearance (time frame: Through study completion, an average of 18 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05450978, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.