<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01730170</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00060793</org_study_id>
    <secondary_id>2U01NS038455-11A1</secondary_id>
    <nct_id>NCT01730170</nct_id>
  </id_info>
  <brief_title>Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD)</brief_title>
  <acronym>MONEAD</acronym>
  <official_title>Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Emmes Company, LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Neurological Disorders and Stroke (NINDS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Epilepsy is one of the most common neurological disorders affecting women of childbearing&#xD;
      age. Poor pregnancy outcomes are increased in these women and their children. The proposed&#xD;
      studies will increase our knowledge on multiple levels to improve care and reduce adverse&#xD;
      outcomes in these mothers and children. An overall goal of this study is to establish the&#xD;
      relationship between antiepileptic drug exposure and outcomes in the mother and child as well&#xD;
      as describe and explain the variability in antiepileptic drug exposure and response.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There is a compelling need for prospective, properly controlled studies in women with&#xD;
      epilepsy (WWE) during pregnancy to improve maternal and child outcomes. The proposed&#xD;
      investigations are pertinent to the National Institute of Neurological Disorders and Stroke&#xD;
      Epilepsy Research Benchmarks and will address multiple gaps in our knowledge noted by the&#xD;
      recent American Academy of Neurology guidelines. This multicenter investigation will employ a&#xD;
      prospective, observational, parallel-group, cohort design with an established research team.&#xD;
&#xD;
      The specific aims are to:&#xD;
&#xD;
        1. Determine if women with epilepsy have increased seizures during pregnancy and delineate&#xD;
           the contributing factors;&#xD;
&#xD;
        2. Determine if C-section rate is increased in women with epilepsy and delineate&#xD;
           contributing factors;&#xD;
&#xD;
        3. Determine if women with epilepsy have an increased risk for depression during pregnancy&#xD;
           and post-partum period and characterize risks factors;&#xD;
&#xD;
        4. Determine the long-term effects of in utero antiepileptic drug exposure on verbal&#xD;
           intellectual abilities and other neurobehavioral outcomes in the children of women with&#xD;
           epilepsy;&#xD;
&#xD;
        5. Determine if small for gestation age and other adverse neonatal outcomes are increased&#xD;
           in children of women with epilepsy;&#xD;
&#xD;
        6. Determine if breastfeeding when taking antiepileptic drugs impairs the child's verbal&#xD;
           intellectual and other cognitive abilities.&#xD;
&#xD;
      An overall goal of the proposed research is to establish the relationship between&#xD;
      antiepileptic drug exposure and outcomes in the mother and child as well as describe and&#xD;
      explain the variability in antiepileptic drug exposure and response.&#xD;
&#xD;
      Anticonvulsant blood levels (ABLs) and area-under-the-concentration-time-curves (AUCs) will&#xD;
      be used as direct measures of drug exposure. The results will enable clinicians to&#xD;
      prospectively calculate individual dosing regimens for the mother in order to optimize dosing&#xD;
      and limit unnecessary drug exposure to the child. In addition, genetic samples will be&#xD;
      collected, which will provide a valuable resource for future pharmacogenetics studies to&#xD;
      further delineate individual variability across patients.&#xD;
&#xD;
      FACTORS ASSESSED IN MONEAD.&#xD;
&#xD;
      Maternal factors: IQ, age, education, employment, ethnic group, maternal and family medical&#xD;
      history including prior pregnancies and psychiatric disorders, socioeconomic status, site,&#xD;
      periconception and pregnancy folate, concomitant medications, alcohol use, tobacco use, or&#xD;
      other drug use during pregnancy, unwanted pregnancy, pregnancy complications, medical&#xD;
      diseases and serious adverse events, McMaster Family Assessment Device (FAD), Block Food&#xD;
      Frequency, and for WWE: types and frequency of seizures or epilepsy, antiepileptic drug&#xD;
      dosages &amp; blood levels, and compliance.&#xD;
&#xD;
      Depression during pregnancy and post-partum as determined by the screening instrument (Beck&#xD;
      Depression Inventory-II; BDI-II), the EPDS (Edinburgh Postnatal Depression Scale) and&#xD;
      confirmed by the Structured Clinical Interview for DSM-IV (SCID), Beck Anxiety Inventory&#xD;
      (BAI), Pittsburgh Sleep Index, and Perceived Stress Scale in mothers, Parental Stress Index,&#xD;
      and Neurological Disorders Depression Inventory in Epilepsy (NDDI-E).&#xD;
&#xD;
      Maternal hormones (estradiol, progesterone) and Vit D will be drawn at Visit 1, 2, 3, 4, 5, 6&#xD;
      and 7. Maternal continine Levels will be collected via urine sample at Visit 3 on all&#xD;
      non-smoking mothers. If the continine result is positive for tobacco smoke exposure, an LC/MS&#xD;
      (liquid chromatography/mass spectrometry test.&#xD;
&#xD;
      Paternal &amp; relative factors: In fathers and a primary maternal relative, the following were&#xD;
      collected: head circumference, IQ estimates, socioeconomic status, dob, race, ethnicity,&#xD;
      family history, and medical history. For the father, marital status, total household income,&#xD;
      employment status. weight, height, and handedness were also collected.&#xD;
&#xD;
      Adult IQ Assessments:&#xD;
&#xD;
      Peabody Picture Vocabulary Test (PPVT), Wechsler's Adult Intelligence Scale (WAIS).&#xD;
&#xD;
      Child factors: enrollment &amp; birth gestational ages, birthweight, breastfeeding, AED levels&#xD;
      when breastfeeding, physical examinations, childhood medical diseases (including congenital&#xD;
      malformations), head circumference, weight, serious adverse events, developmental delays, and&#xD;
      special education. Also, obtained premature delivery, APGARs (1 &amp; 5 minutes), Neonatal&#xD;
      Intensive Care Unit admissions and all admissions &gt;12hrs, hypoglycemia (&lt;45), need for&#xD;
      resuscitation, and neonatal death. Child Hgb, Hct, PKU, TSH, and T4 at delivery from med&#xD;
      records if collected.&#xD;
&#xD;
      Child Cognitive/Behavioral Assessments:&#xD;
&#xD;
      Denver II, Behavior Assessment System for Children - Parent (BASCP-2) and Teacher (BASCT-2),&#xD;
      Behavior Rating Inventory of Executive Functioning Preschool (BRIEFP) and version 2&#xD;
      (BRIEF-2), Adaptive Behavior Assessment Scale 3 (ABAS-3), Modified Checklist for Autism in&#xD;
      Toddlers (M-CHAT), Modified Edinburgh Handedness Inventory, Gilliam Autism Rating Scale 3&#xD;
      (GARS-3), Bayley Scales of Infant and Toddler Development-3 (BSID-III), Differential&#xD;
      Abilities Scale-II (DAS-II), Preschool Language Scale-5 (PLS-5), Peabody Picture Vocabulary&#xD;
      Test-4 (PPVT-4), Beery-Buktenica Developmental Test of Visual-Motor Integration-6 (VMI-6),&#xD;
      Torrance Test of Creative Thinking- Figural (TTCT-F), NEuroPSYchological Assessment 2nd&#xD;
      edition (NEPSY2), Expressive One Word Picture Vocabulary Test-4 (EOWPVT4), Wechsler's&#xD;
      Intelligence Scale for Children 5 (WISC5) Coding subtest, Children's Memory Scale (CMS),&#xD;
      Lafayette Grooved Pegboard (GPB), Wide Range Achievement Test 5th edition (WRAT5), and Social&#xD;
      Responsiveness Scale 2&#xD;
&#xD;
      Verbal intellectual ability at age 6 years is the ultimate primary outcome. It is determined&#xD;
      by Verbal Index which is average of Word Definitions and Verbal Similarities subtests from&#xD;
      the Differential Ability Scales-2nd ed. (DAS-II),50 -School Age Level, Expressive One-Word&#xD;
      Picture Vocabulary Test-4,51 the Phonological Processing, Comprehension of Instructions and&#xD;
      Sentence Repetition subscales from the NEPSY-2 57 and the Peabody Picture Vocabulary Test-4th&#xD;
      ed. (PPVT-4).52 Children will not reach age 6 in this initial grant period, so primary&#xD;
      outcome at age 2 will be the Language Scale from the Bayley Scales of Infant &amp; Toddler&#xD;
      Development-III.&#xD;
&#xD;
      Cerebral Lateralization will be assessed as verbal minus non-verbal difference scores and&#xD;
      proportion of dextrals in PWWE vs. HPW and in their children as assessed by the Edinburgh&#xD;
      Handedness Inventory.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2013</start_date>
  <completion_date type="Actual">December 12, 2022</completion_date>
  <primary_completion_date type="Actual">December 12, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in seizure frequency over pregnancy vs. post-partum (comparable time periods for non-pregnant women with epilepsy).</measure>
    <time_frame>Pregnant women with epilepsy:1st Trimester through 9 months post-partum; Nonpregnant women with epilepsy: Study enrollment through 18 months participation</time_frame>
    <description>Change in seizure frequency during pregnancy vs postpartum as measured by subject completed daily electronic seizure diaries</description>
  </primary_outcome>
  <primary_outcome>
    <measure>C-section Rate</measure>
    <time_frame>Pregnant women with epilepsy &amp; Pregnant women without epilepsy at child's birth</time_frame>
    <description>rate of C-sections in pregnant women without epilepsy vs pregnant women with epilepsy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rate of Depression</measure>
    <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</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Child Intellectual Ability (2YO)</measure>
    <time_frame>When child is 2 Years of age</time_frame>
    <description>Child intellectual ability as measured by the Language Scale of the Bayley Scales of Infant Development -III at visit 9 (2YO). All of the outcome measures for cognitive outcomes at the various ages are scale scores which are continuous with a mean of 100 and a standard deviation of 15.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Child Intellectual Ability (4.5 YO)</measure>
    <time_frame>When child is 4.5 Years of age</time_frame>
    <description>Child intellectual ability as measured by the Torrence Test of Creative Thinking at visit 11 (4.5YO). All of the outcome measures for cognitive outcomes at the various ages are scale scores which are continuous with a mean of 100 and a standard deviation of 15.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Child Intellectual Ability (3 and 6 YO)</measure>
    <time_frame>When child is 3 and 6 Years of age</time_frame>
    <description>Child intellectual ability as measured by the Verbal Index Score at visit 10 (3YO) and visit 12 (6YO). All of the outcome measures for cognitive outcomes at the various ages are scale scores which are continuous with a mean of 100 and a standard deviation of 15.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Small for Gestational Age Rate</measure>
    <time_frame>Child's birth</time_frame>
    <description>Rate of children considered small for gestational age (&lt;10%tile)born to women with epilepsy vs women without epilepsy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Breastfeeding Effects on verbal intellectual ability in children</measure>
    <time_frame>Birth until the child is 2 Years of age, although we anticipate not all children will breastfeed until 2 Years</time_frame>
    <description>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.</description>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">565</enrollment>
  <condition>Epilepsy</condition>
  <condition>Pregnancy</condition>
  <arm_group>
    <arm_group_label>Pregnant Women without Epilepsy</arm_group_label>
    <description>Women in their first trimester of pregnancy who are not diagnosed with epilepsy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Nonpregnant Women with Epilepsy</arm_group_label>
    <description>Women diagnosed with epilepsy and not currently pregnant.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pregnant Women with Epilepsy</arm_group_label>
    <description>Women in their first trimester of pregnancy and diagnosed with epilepsy</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum, cheek cells, urine&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Subjects will be recruited by the investigators from their clinic populations and&#xD;
        advertisements.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria for All Women&#xD;
&#xD;
          -  Pregnant women with epilepsy up to 20 weeks gestation, healthy pregnant women without&#xD;
             epilepsy up to 20 weeks gestation, or non-pregnant women with epilepsy.&#xD;
&#xD;
          -  Ability to maintain a daily medical diary.&#xD;
&#xD;
          -  Language skills in English or Spanish adequate to perform the cognitive tests and&#xD;
             questionnaires.&#xD;
&#xD;
          -  Access to a telephone for phone contacts.&#xD;
&#xD;
          -  Age 14-45 inclusive.&#xD;
&#xD;
        Inclusion Criteria applicable for pregnant women only. -Ability for follow-up through 6&#xD;
        years after giving birth.&#xD;
&#xD;
        Criteria applicable for non-pregnant women with epilepsy only:&#xD;
&#xD;
          -  Minimum of 9 months post live birth, miscarriage, or elective termination.&#xD;
&#xD;
          -  Not currently breastfeeding.&#xD;
&#xD;
        Exclusion Criteria for All Women&#xD;
&#xD;
          -  Women with an expected IQ&lt;70.&#xD;
&#xD;
          -  IV drug use in past year or any of the following since the beginning of pregnancy:&#xD;
             Alcohol abuse, cocaine, or methamphetamine) or sequelae of drug/alcohol abuse.&#xD;
&#xD;
          -  History of psychogenic non-epileptic spells.&#xD;
&#xD;
          -  History of positive Syphilis test.&#xD;
&#xD;
          -  History of HIV positive test.&#xD;
&#xD;
          -  Progressive cerebral disease (e.g., multiple sclerosis, progressive brain tumor).&#xD;
&#xD;
          -  Presence of other major medical illness (e.g., diabetes, cancer).&#xD;
&#xD;
          -  Any medical, psychiatric, or other condition that, in the judgment of the&#xD;
             investigator, is a contraindication to protocol participation or impairs ability to&#xD;
             give informed consent.&#xD;
&#xD;
          -  Concurrent participation in an experimental drug trial.&#xD;
&#xD;
        Exclusion criteria applicable for pregnant women only.&#xD;
&#xD;
          -  Exposure to known teratogens during pregnancy, excluding AEDs.&#xD;
&#xD;
          -  Detection of fetal major congenital malformation prior to enrollment in current&#xD;
             pregnancy.&#xD;
&#xD;
          -  History of a known genetic disorder in herself or a primary relative (may contact&#xD;
             MONEAD team with details for possible exception).&#xD;
&#xD;
          -  Use of non-licensed midwife as primary source of natal care and/or planning home&#xD;
             delivery or delivery at a stand-alone birth center, independent from a hospital.&#xD;
&#xD;
        Exclusion criteria applicable for all women with epilepsy.&#xD;
&#xD;
        -Planned surgical intervention for epilepsy that would occur during the subject's&#xD;
        participation in the project&#xD;
&#xD;
        Exclusion criteria applicable for pregnant women with epilepsy only. -History of switching&#xD;
        AEDs during pregnancy prior to enrollment. &quot;Switching&quot; AEDs includes changing from no AED&#xD;
        therapy to therapy, discontinuing a current AED therapy, or changing to a different AED&#xD;
        therapy.&#xD;
&#xD;
        Exclusion criteria applicable for non-pregnant women only.&#xD;
&#xD;
          -  Diagnosed by a health care professional as perimenopausal or postmenopausal.&#xD;
&#xD;
          -  History of switching AEDs within 90 days of enrollment. &quot;Switching&quot; AEDs includes&#xD;
             changing from no AED therapy to therapy, discontinuing a current AED therapy, or&#xD;
             changing to a different AED therapy.&#xD;
&#xD;
        Inclusion Criteria for Study Family Members&#xD;
&#xD;
          -  The Father must be the biological father of the child in the study.&#xD;
&#xD;
          -  The Maternal Relative must be a full biological relative or half-sibling of the mother&#xD;
             chosen by the following hierarchy:&#xD;
&#xD;
               1. st choice: Sister of closest age to the mother in the trial&#xD;
&#xD;
               2. nd Sister of next closest age&#xD;
&#xD;
               3. rd Brother of closest age&#xD;
&#xD;
               4. th Brother of next closest age&#xD;
&#xD;
               5. th Mother&#xD;
&#xD;
               6. th Father of pregnant mother in the study&#xD;
&#xD;
               7. th Half-Sibling if NO Primary FULL relatives are available.&#xD;
&#xD;
                  Exclusion Criteria for Study Family Members&#xD;
&#xD;
          -  Any medical, psychiatric, or other condition that, in the judgment of the&#xD;
             investigator, is a contraindication to protocol participation or impairs ability to&#xD;
             give informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>14 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kimford J Meador, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Page B Pennell, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Abigail Matthews, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Emmes Company, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama Birmingham Hospital- UAB</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294-0021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Arizona - University Medical Center</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85724-5023</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Keck Hospital of the University of Southern California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90089</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami Hospital - University of Miami School of Medicine</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University School of Medicine</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Georgia at Georgia Regents University</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912-0004</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern Memorial Hospital-Northwestern University Feinberg School of Medicine</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Hopkins Bayview Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224-2735</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham &amp; Women's Hospital - Harvard</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115-6110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202-2608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Epilepsy Group</name>
      <address>
        <city>Roseville</city>
        <state>Minnesota</state>
        <zip>55113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Shore Jewish Medical Center</name>
      <address>
        <city>Manhasset</city>
        <state>New York</state>
        <zip>11040-1402</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York University School of Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016-6402</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center/NY Presbyterian Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032-7133</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest Baptist Health-Wake Forest University School of Medicine</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati UC Health University Hospital</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267-0525</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Center</name>
      <address>
        <city>Danville</city>
        <state>Pennsylvania</state>
        <zip>17822-9800</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>November 9, 2012</study_first_submitted>
  <study_first_submitted_qc>November 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>July 10, 2023</last_update_submitted>
  <last_update_submitted_qc>July 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Kimford Jay Meador</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Epilepsy</keyword>
  <keyword>Pregnancy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epilepsy</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 17, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/70/NCT01730170/Prot_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01730170
org study id: IRB00060793
secondary id: 2U01NS038455-11A1
nct id: NCT01730170
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
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.

      FACTORS ASSESSED IN MONEAD.

      Maternal factors: IQ, age, education, employment, ethnic group, maternal and family medical
      history including prior pregnancies and psychiatric disorders, socioeconomic status, site,
      periconception and pregnancy folate, concomitant medications, alcohol use, tobacco use, or
      other drug use during pregnancy, unwanted pregnancy, pregnancy complications, medical
      diseases and serious adverse events, McMaster Family Assessment Device (FAD), Block Food
      Frequency, and for WWE: types and frequency of seizures or epilepsy, antiepileptic drug
      dosages & blood levels, and compliance.

      Depression during pregnancy and post-partum as determined by the screening instrument (Beck
      Depression Inventory-II; BDI-II), the EPDS (Edinburgh Postnatal Depression Scale) and
      confirmed by the Structured Clinical Interview for DSM-IV (SCID), Beck Anxiety Inventory
      (BAI), Pittsburgh Sleep Index, and Perceived Stress Scale in mothers, Parental Stress Index,
      and Neurological Disorders Depression Inventory in Epilepsy (NDDI-E).

      Maternal hormones (estradiol, progesterone) and Vit D will be drawn at Visit 1, 2, 3, 4, 5, 6
      and 7. Maternal continine Levels will be collected via urine sample at Visit 3 on all
      non-smoking mothers. If the continine result is positive for tobacco smoke exposure, an LC/MS
      (liquid chromatography/mass spectrometry test.

      Paternal & relative factors: In fathers and a primary maternal relative, the following were
      collected: head circumference, IQ estimates, socioeconomic status, dob, race, ethnicity,
      family history, and medical history. For the father, marital status, total household income,
      employment status. weight, height, and handedness were also collected.

      Adult IQ Assessments:

      Peabody Picture Vocabulary Test (PPVT), Wechsler's Adult Intelligence Scale (WAIS).

      Child factors: enrollment & birth gestational ages, birthweight, breastfeeding, AED levels
      when breastfeeding, physical examinations, childhood medical diseases (including congenital
      malformations), head circumference, weight, serious adverse events, developmental delays, and
      special education. Also, obtained premature delivery, APGARs (1 & 5 minutes), Neonatal
      Intensive Care Unit admissions and all admissions >12hrs, hypoglycemia (<45), need for
      resuscitation, and neonatal death. Child Hgb, Hct, PKU, TSH, and T4 at delivery from med
      records if collected.

      Child Cognitive/Behavioral Assessments:

      Denver II, Behavior Assessment System for Children - Parent (BASCP-2) and Teacher (BASCT-2),
      Behavior Rating Inventory of Executive Functioning Preschool (BRIEFP) and version 2
      (BRIEF-2), Adaptive Behavior Assessment Scale 3 (ABAS-3), Modified Checklist for Autism in
      Toddlers (M-CHAT), Modified Edinburgh Handedness Inventory, Gilliam Autism Rating Scale 3
      (GARS-3), Bayley Scales of Infant and Toddler Development-3 (BSID-III), Differential
      Abilities Scale-II (DAS-II), Preschool Language Scale-5 (PLS-5), Peabody Picture Vocabulary
      Test-4 (PPVT-4), Beery-Buktenica Developmental Test of Visual-Motor Integration-6 (VMI-6),
      Torrance Test of Creative Thinking- Figural (TTCT-F), NEuroPSYchological Assessment 2nd
      edition (NEPSY2), Expressive One Word Picture Vocabulary Test-4 (EOWPVT4), Wechsler's
      Intelligence Scale for Children 5 (WISC5) Coding subtest, Children's Memory Scale (CMS),
      Lafayette Grooved Pegboard (GPB), Wide Range Achievement Test 5th edition (WRAT5), and Social
      Responsiveness Scale 2

      Verbal intellectual ability at age 6 years is the ultimate primary outcome. It is determined
      by Verbal Index which is average of Word Definitions and Verbal Similarities subtests from
      the Differential Ability Scales-2nd ed. (DAS-II),50 -School Age Level, Expressive One-Word
      Picture Vocabulary Test-4,51 the Phonological Processing, Comprehension of Instructions and
      Sentence Repetition subscales from the NEPSY-2 57 and the Peabody Picture Vocabulary Test-4th
      ed. (PPVT-4).52 Children will not reach age 6 in this initial grant period, so primary
      outcome at age 2 will be the Language Scale from the Bayley Scales of Infant & Toddler
      Development-III.

      Cerebral Lateralization will be assessed as verbal minus non-verbal difference scores and
      proportion of dextrals in PWWE vs. HPW and in their children as assessed by the Edinburgh
      Handedness Inventory.
observational model: Cohort
time perspective: Prospective
measure: Change 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
description: Change in seizure frequency during pregnancy vs postpartum as measured by subject completed daily electronic seizure diaries
measure: C-section Rate
time frame: Pregnant women with epilepsy & Pregnant women without epilepsy at child's birth
description: rate of C-sections in pregnant women without epilepsy vs pregnant women with epilepsy
measure: 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
description: 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.
measure: Child Intellectual Ability (2YO)
time frame: When child is 2 Years of age
description: Child intellectual ability as measured by the Language Scale of the Bayley Scales of Infant Development -III at visit 9 (2YO). All of the outcome measures for cognitive outcomes at the various ages are scale scores which are continuous with a mean of 100 and a standard deviation of 15.
measure: Child Intellectual Ability (4.5 YO)
time frame: When child is 4.5 Years of age
description: Child intellectual ability as measured by the Torrence Test of Creative Thinking at visit 11 (4.5YO). All of the outcome measures for cognitive outcomes at the various ages are scale scores which are continuous with a mean of 100 and a standard deviation of 15.
measure: Child Intellectual Ability (3 and 6 YO)
time frame: When child is 3 and 6 Years of age
description: Child intellectual ability as measured by the Verbal Index Score at visit 10 (3YO) and visit 12 (6YO). All of the outcome measures for cognitive outcomes at the various ages are scale scores which are continuous with a mean of 100 and a standard deviation of 15.
measure: Small for Gestational Age Rate
time frame: Child's birth
description: Rate of children considered small for gestational age (<10%tile)born to women with epilepsy vs women without epilepsy
measure: 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
description: 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.
arm group label: Pregnant Women without Epilepsy
description: Women in their first trimester of pregnancy who are not diagnosed with epilepsy
arm group label: Nonpregnant Women with Epilepsy
description: Women diagnosed with epilepsy and not currently pregnant.
arm group label: Pregnant Women with Epilepsy
description: Women in their first trimester of pregnancy and diagnosed with epilepsy
Serum, cheek cells, urine
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 14 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kimford J Meador, M.D.
role: Principal Investigator
affiliation: Stanford University
last name: Page B Pennell, M.D.
role: Principal Investigator
affiliation: University of Pittsburgh
last name: Abigail Matthews, PhD
role: Principal Investigator
affiliation: The Emmes Company, LLC
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Kimford Jay Meador
investigator title: Professor
mesh term: Epilepsy
provided document: 