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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Emory University
Sponsor:
Collaborator:
The EMMES Corporation
Information provided by (Responsible Party):
kmeador@stanford.edu, Emory University
ClinicalTrials.gov Identifier:
NCT01730170
First received: November 9, 2012
Last updated: November 13, 2014
Last verified: November 2014
  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


Estimated Enrollment: 550
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
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

Contacts
Contact: Gene Moore 843-261-4805 emoore5@emory.edu

Locations
United States, Alabama
University of Alabama Birmingham Hospital- UAB Recruiting
Birmingham, Alabama, United States, 35294-0021
Contact: Cheryl Hall, LPN    205-934-1654    chall@uab.edu   
Principal Investigator: Jennifer L DeWolfe, DO, DABPN         
United States, Arizona
University of Arizona - University Medical Center Recruiting
Tucson, Arizona, United States, 85724-5023
Contact: Lucia Rodriguez    520-626-3576    lrodriguez@neurology.arizona.edu   
Principal Investigator: David M Labiner, M.D.         
United States, California
Keck Hospital of the University of Southern California Recruiting
Los Angeles, California, United States, 90089
Contact: Guadalupe Corral-Leyva    323-442-7057    corralle@usc.edu   
Principal Investigator: Laura Kalayjian, M.D.         
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Swetapadma Patnaik    650-497-6810    sweta@stanford.edu   
Principal Investigator: Kimford J Meador, MD         
United States, Florida
University of Miami Hospital - University of Miami School of Medicine Recruiting
Miami, Florida, United States, 33136
Contact: Pedro Figueredo, M.D.    305-243-8829    PFigueredo@med.miami.edu   
Principal Investigator: Enrique A Serrano, M.D.         
United States, Georgia
Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30322
Contact: Melanee Newman    404-778-4249    melanee_newman@emoryhealthcare.org   
Principal Investigator: Kimford J Meador, M.D.         
Sub-Investigator: Naymee Velez-Ruiz, MD         
Medical College of Georgia at Georgia Regents University Recruiting
Augusta, Georgia, United States, 30912-0004
Contact: Patty Ray, Ph.D.    706-721-6260    paray@gru.edu   
Principal Investigator: Suzanne Strickland, M.D.         
United States, Illinois
Northwestern Memorial Hospital-Northwestern University Feinberg School of Medicine Recruiting
Chicago, Illinois, United States, 60611
Contact: Irena Garic    312-926-1672    igaric@nmff.org   
Principal Investigator: Elizabeth Gerard, M.D.         
United States, Maryland
John Hopkins Bayview Medical Center Recruiting
Baltimore, Maryland, United States, 21224-2735
Contact: Pam Coe    410-502-5570    pcoe@jhmi.edu   
Principal Investigator: Gregory Krauss, MD         
United States, Massachusetts
Brigham & Women's Hospital - Harvard Recruiting
Boston, Massachusetts, United States, 02115-6110
Contact: Rutendo Kashambwa    617-525-3011    RKASHAMBWA@PARTNERS.ORG   
Principal Investigator: Page B Pennell, M.D.         
United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202-2608
Contact: Carla Sandles    313-916-3923    CSANDLE1@hfhs.org   
Principal Investigator: Gregory L Barkley, M.D.         
United States, Minnesota
Minnesota Epilepsy Group Recruiting
St. Paul, Minnesota, United States, 55102-2533
Contact: Janet Branson    651-241-5595    jbranson@mnepilepsy.net   
Principal Investigator: Patricia E Penovich, M.D.         
United States, New York
North Shore Jewish Medical Center Recruiting
Manhasset, New York, United States, 11040-1402
Contact: Connie Lau, M.S.    516-325-7022    CLau@NSHS.edu   
Principal Investigator: Cynthia L Harden, M.D.         
Columbia University Medical Center/NY Presbyterian Hospital Recruiting
New York, New York, United States, 10032-7133
Contact: Jackie Wooley    212-305-1684    jw3186@columbia.edu   
Principal Investigator: Alison Pack, M.D.         
New York University School of Medicine Recruiting
New York, New York, United States, 10016-6402
Contact: Veronique Ruppe    646-558-0877    Veronique.Ruppe@nyumc.org   
Principal Investigator: Jacqueline A French, M.D.         
United States, North Carolina
Wake Forest Baptist Health-Wake Forest University School of Medicine Recruiting
Winston Salem, North Carolina, United States, 27157
Contact: Jessica Dimos    336-716-1715    jdimos@wakehealth.edu   
Principal Investigator: Maria C Sam, M.D.         
United States, Ohio
University of Cincinnati UC Health University Hospital Recruiting
Cincinnati, Ohio, United States, 45267-0525
Contact: Lucy Mendoza, CCRP    513-558-3020    mendozlc@UCMAIL.UC.EDU   
Principal Investigator: Jennifer Cavitt, M.D.         
United States, Pennsylvania
Geisinger Medical Center Recruiting
Danville, Pennsylvania, United States, 17822-9800
Contact: Rosemarie Delucca    570-808-3461    rtdelucca@geisinger.edu   
Principal Investigator: Paul McCabe, MD         
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Kaylee Klingensmith    412-864-2401    klingensmithk@upmc.edu   
Principal Investigator: Anto Bagic, M.D.         
United States, Washington
University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98104
Contact: Stephanie Mallahan    206-744-6324    steph22@uw.edu   
Principal Investigator: John W Miller, M.D., Ph.D.         
Sponsors and Collaborators
Emory University
The EMMES Corporation
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:
No publications provided

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: November 13, 2014
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
Central Nervous System Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014