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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
The EMMES Corporation
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
kmeador@stanford.edu, Emory University
ClinicalTrials.gov Identifier:
NCT01730170
First received: November 9, 2012
Last updated: February 12, 2016
Last verified: February 2016
  Purpose
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.

Condition
Epilepsy
Pregnancy

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • 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.


Biospecimen Retention:   Samples With DNA
Serum, cheek cells, urine

Enrollment: 565
Study Start Date: January 2013
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   14 Years to 45 Years   (Child, Adult)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Subjects will be recruited by the investigators from their clinic populations and advertisements.
Criteria

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.

Inclusion 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 live birth, miscarriage, or elective termination.
  • 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 in current pregnancy.
  • History of a known genetic disorder in herself or a primary relative (may contact MONEAD team with details for possible exception).
  • Use of non-licensed midwife as primary source of natal care and/or planning home delivery or delivery at a stand-alone birth center, independent from a hospital.

Exclusion criteria applicable for all women with epilepsy.

-Planned surgical intervention for epilepsy that would occur during the subject's participation in the project

Exclusion criteria applicable for pregnant women with epilepsy only. -History of switching AEDs during pregnancy prior to enrollment. "Switching" AEDs includes changing from no AED therapy to therapy, discontinuing a current AED therapy, or changing to a different AED therapy.

Exclusion criteria applicable for non-pregnant women only.

  • Diagnosed by a health care professional as perimenopausal or postmenopausal.
  • History of switching AEDs within 90 days of enrollment. "Switching" AEDs includes changing from no AED therapy to therapy, discontinuing a current AED therapy, or changing to a different AED therapy.

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 or half-sibling 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
    7. th Half-Sibling if NO Primary FULL relatives are available.

      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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01730170

Locations
United States, Alabama
University of Alabama Birmingham Hospital- UAB
Birmingham, Alabama, United States, 35294-0021
United States, Arizona
University of Arizona - University Medical Center
Tucson, Arizona, United States, 85724-5023
United States, California
Keck Hospital of the University of Southern California
Los Angeles, California, United States, 90089
Stanford University
Stanford, California, United States, 94305
United States, Florida
University of Miami Hospital - University of Miami School of Medicine
Miami, Florida, United States, 33136
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
Medical College of Georgia at Georgia Regents University
Augusta, Georgia, United States, 30912-0004
United States, Illinois
Northwestern Memorial Hospital-Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States, 60611
United States, Maryland
John Hopkins Bayview Medical Center
Baltimore, Maryland, United States, 21224-2735
United States, Massachusetts
Brigham & Women's Hospital - Harvard
Boston, Massachusetts, United States, 02115-6110
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202-2608
United States, Minnesota
Minnesota Epilepsy Group
St. Paul, Minnesota, United States, 55102-2533
United States, New York
North Shore Jewish Medical Center
Manhasset, New York, United States, 11040-1402
New York University School of Medicine
New York, New York, United States, 10016-6402
Columbia University Medical Center/NY Presbyterian Hospital
New York, New York, United States, 10032-7133
United States, North Carolina
Wake Forest Baptist Health-Wake Forest University School of Medicine
Winston Salem, North Carolina, United States, 27157
United States, Ohio
University of Cincinnati UC Health University Hospital
Cincinnati, Ohio, United States, 45267-0525
United States, Pennsylvania
Geisinger Medical Center
Danville, Pennsylvania, United States, 17822-9800
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Emory University
The EMMES Corporation
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Principal Investigator: Kimford J Meador, M.D. Emory University
Principal Investigator: Page B Pennell, M.D. Brigham & Women's Hospital - Harvard
  More Information

Additional Information:
Responsible Party: kmeador@stanford.edu, Professor, Emory University
ClinicalTrials.gov Identifier: NCT01730170     History of Changes
Other Study ID Numbers: IRB00060793  2U01NS038455-11A1 
Study First Received: November 9, 2012
Last Updated: February 12, 2016
Health Authority: United States: Federal Government

Keywords provided by Emory University:
Epilepsy
Pregnancy

Additional relevant MeSH terms:
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Anticonvulsants

ClinicalTrials.gov processed this record on December 02, 2016