Maternal and Neurodevelopmental Outcomes of in Utero Antiepileptic Drug (AED) Exposure (MONEAD)

This study is currently recruiting participants.
Verified March 2014 by Emory University
Sponsor:
Collaborator:
The EMMES Corporation
Information provided by (Responsible Party):
Kimford J. Meador, MD, Emory University
ClinicalTrials.gov Identifier:
NCT01730170
First received: November 9, 2012
Last updated: March 6, 2014
Last verified: March 2014

November 9, 2012
March 6, 2014
January 2013
July 2017   (final data collection date for primary outcome measure)
  • Changes in seizure frequency over pregnancy vs. post-partum (comparable time periods for non-pregnant women with epilepsy). [ Time Frame: Pregnant women with epilepsy:1st Trimester through 9 months post-partum; Nonpregnant women with epilepsy: Study enrollment through 18 months participation ] [ Designated as safety issue: No ]
    Change in seizure frequency during pregnancy vs postpartum as measured by subject completed daily electronic seizure diaries
  • C-section Rate [ Time Frame: Pregnant women with epilepsy & Pregnant women without epilepsy at child's birth ] [ Designated as safety issue: No ]
    rate of C-sections in pregnant women without epilepsy vs pregnant women with epilepsy
  • Rate of Depression [ Time Frame: Pregnant women: 1st Trimester through 9 months post partum, again when child is 2 and 3 Years of age. Nonpregnant women with epilepsy: Study enrollment through 6months participation, then 12 months until 18 months participation ] [ Designated as safety issue: Yes ]
    Rate of depression during pregnancy in pregnant women with epilepsy vs pregnant women without epilepsy screened by the Beck Depression Inventory and confirmed by the Structured Clinical Interview for Diagnostic and Statistical Manual-IV.
  • Child Verbal Intellectual Ability [ Time Frame: When child is 2, 3, 4.5 and 6 Years of age ] [ Designated as safety issue: No ]
    Child verbal intellectual ability as measured by the Language Scale of the Bayley Scales of Infant Development -III at visit 9 (2Yo) and by the Differential Abilities Scale-II at visit 10 (3Yo)and 4.5YO and 6YO.
  • Small for Gestational Age Rate [ Time Frame: Child's birth ] [ Designated as safety issue: No ]
    Rate of children considered small for gestational age (<10%tile)born to women with epilepsy vs women without epilepsy
  • Breastfeeding Effects on verbal intellectual ability in children [ Time Frame: Birth until the child is 2 Years of age, although we anticipate not all children will breastfeed until 2 Years ] [ Designated as safety issue: No ]
    Measuring difference in verbal intellectual ability in breastfed children vs non-breastfed children born to women on aeds via the Bayley Scales of Infant Development III Language scale at 2 years of age and Differential Abilities Scale III at 3, 4.5 and 6 Years of age.
Same as current
Complete list of historical versions of study NCT01730170 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Maternal and Neurodevelopmental Outcomes of in Utero Antiepileptic Drug (AED) Exposure
Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs

Epilepsy is one of the most common neurological disorders affecting women of childbearing age. Poor pregnancy outcomes are increased in these women and their children. The proposed studies will increase our knowledge on multiple levels to improve care and reduce adverse outcomes in these mothers and children. An overall goal of this study is to establish the relationship between antiepileptic drug exposure and outcomes in the mother and child as well as describe and explain the variability in antiepileptic drug exposure and response.

There is a compelling need for prospective, properly controlled studies in women with epilepsy (WWE) during pregnancy to improve maternal and child outcomes. The proposed investigations are pertinent to the National Institute of Neurological Disorders and Stroke Epilepsy Research Benchmarks and will address multiple gaps in our knowledge noted by the recent American Academy of Neurology guidelines. This multicenter investigation will employ a prospective, observational, parallel-group, cohort design with an established research team.

The specific aims are to:

  1. Determine if women with epilepsy have increased seizures during pregnancy and delineate the contributing factors;
  2. Determine if C-section rate is increased in women with epilepsy and delineate contributing factors;
  3. Determine if women with epilepsy have an increased risk for depression during pregnancy and post-partum period and characterize risks factors;
  4. Determine the long-term effects of in utero antiepileptic drug exposure on verbal intellectual abilities and other neurobehavioral outcomes in the children of women with epilepsy;
  5. Determine if small for gestation age and other adverse neonatal outcomes are increased in children of women with epilepsy;
  6. Determine if breastfeeding when taking antiepileptic drugs impairs the child's verbal intellectual and other cognitive abilities.

An overall goal of the proposed research is to establish the relationship between antiepileptic drug exposure and outcomes in the mother and child as well as describe and explain the variability in antiepileptic drug exposure and response.

Anticonvulsant blood levels (ABLs) and area-under-the-concentration-time-curves (AUCs) will be used as direct measures of drug exposure. The results will enable clinicians to prospectively calculate individual dosing regimens for the mother in order to optimize dosing and limit unnecessary drug exposure to the child. In addition, genetic samples will be collected, which will provide a valuable resource for future pharmacogenetics studies to further delineate individual variability across patients.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

Serum, cheek cells, urine

Non-Probability Sample

Subjects will be recruited by the investigators from their clinic populations and advertisements.

  • Epilepsy
  • Pregnancy
Not Provided
  • Pregnant Women without Epilepsy
    Women in their first trimester of pregnancy who are not diagnosed with epilepsy
  • Nonpregnant Women with Epilepsy
    Women diagnosed with epilepsy and not currently pregnant.
  • Pregnant Women with Epilepsy
    Women in their first trimester of pregnancy and diagnosed with epilepsy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
550
July 2017
July 2017   (final data collection date for primary outcome measure)

Inclusion Criteria for All Women

  • Pregnant women with epilepsy up to 20 weeks gestation, healthy pregnant women without epilepsy up to 20 weeks gestation, or non-pregnant women with epilepsy.
  • Ability to maintain a daily medical diary.
  • Language skills in English or Spanish adequate to perform the cognitive tests and questionnaires.
  • Access to a telephone for phone contacts.
  • Age 14-45 inclusive.

Criteria applicable for pregnant women only.

  • Ability for follow-up through 6 years after giving birth.

Criteria applicable for non-pregnant women with epilepsy only:

  • Minimum of 9 months post-partum
  • Not currently breastfeeding

Exclusion Criteria for All Women

  • Women with an expected IQ<70.
  • IV drug use in past year or any of the following since the beginning of pregnancy: Alcohol abuse, cocaine, or methamphetamine) or sequelae of drug/alcohol abuse.
  • History of psychogenic non-epileptic spells.
  • History of positive Syphilis test.
  • History of HIV positive test.
  • Progressive cerebral disease (e.g., multiple sclerosis, progressive brain tumor).
  • Presence of other major medical illness (e.g., diabetes, cancer).
  • Any medical, psychiatric, or other condition that, in the judgment of the investigator, is a contraindication to protocol participation or impairs ability to give informed consent.
  • Concurrent participation in an experimental drug trial

Exclusion criteria applicable for pregnant women only.

  • Exposure to known teratogens during pregnancy, excluding AEDs.
  • Detection of fetal major congenital malformation prior to enrollment.
  • History of a known genetic disorder in herself or a primary relative (may contact MONEAD team with details for possible exception).
  • Use of midwife as primary source of natal care or planning home delivery.

Exclusion criteria applicable for pregnant women with epilepsy only.

  • History of switching AEDs during pregnancy prior to enrollment

Exclusion criteria applicable for non-pregnant women only.

  • Diagnosed by a health care professional as perimenopausal or postmenopausal.

Inclusion Criteria for Study Family Members

  • The Father must be the biological father of the child in the study.
  • The Maternal Relative must be a full biological relative of the mother chosen by the following hierarchy:

    1. st choice: Sister of closest age to the mother in the trial
    2. nd. Sister of next closest age
    3. rd. Brother of closest age
    4. th. Brother of next closest age
    5. th. Mother
    6. th. Father of pregnant mother in the study

Exclusion Criteria for Study Family Members

  • Any medical, psychiatric, or other condition that, in the judgment of the investigator, is a contraindication to protocol participation or impairs ability to give informed consent.
Female
14 Years to 45 Years
Yes
Contact: Gene Moore 843-261-4805 emoore5@emory.edu
United States
 
NCT01730170
IRB00060793, 2U01NS038455-11A1
No
Kimford J. Meador, MD, Emory University
Emory University
The EMMES Corporation
Principal Investigator: Kimford J Meador, M.D. Emory University
Principal Investigator: Page B Pennell, M.D. Brigham & Women's Hospital - Harvard
Emory University
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP