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

NCT05450978 | Recruiting DMC FDA Drug

• 2 other identifiers: STUDY21090138R01HD105305
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Epilepsy; Pregnancy Related

Outcome Measures

Primary Outcomes (1)

• 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.

  Through study completion, an average of 18 months.

Secondary Outcomes (3)

• Seizure Frequency

  Through study completion, an average of 18 months.

• Anti-seizure Medication (ASM) Side Effects

  Through study completion, an average of 18 months

• Placental passage of Anti-Seizure Medications (ASM)

  Through study completion, an average of 18 months

Study Arms (3)

Lamotrigine (LTG)

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

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)

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)

Drug: Oxcarbazepine

Interventions

Lamotrigine DRUG

Anti-seizure concentrations

Also known as: Anti-seizure medication: Lamotrigine (LTG)

Lamotrigine (LTG)

Levetiracetam DRUG

Anti-seizure concentrations

Also known as: Anti-seizure medication: Levetiracetam (LEV)

Levetiracetam (LEV)

Oxcarbazepine DRUG

Anti-seizure concentrations

Also known as: Anti-seizure medication: Oxcarbazepine (OXC)

Oxcarbazepine (OXC)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Women with Epilepsy
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Participants to be mainly recruited from Neurology and OBGYN clinics.

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Pittsburgh: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Related Publications (3)

• 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.

  PMID: 33369356 BACKGROUND

• 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.

  PMID: 31886825 BACKGROUND

• 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.

  PMID: 35157004 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood, urine, breast milk, umbilical cord blood

MeSH Terms

Conditions

Epilepsy

Interventions

Lamotrigine; Levetiracetam; Oxcarbazepine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Carbamazepine; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Page B Pennell, MD

  The University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tonge Ebai, PhD

CONTACT

4126160730; ebait@upmc.edu

Erica Kemp, PA

CONTACT

kempe2@upmc.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 22, 2022
• First Posted: July 11, 2022
• Study Start: July 20, 2022
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (1)