<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/NCT03774641</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00162134</org_study_id>
    <nct_id>NCT03774641</nct_id>
  </id_info>
  <brief_title>A Pilot Study of Prophylactic Management of Lamotrigine in Pregnant Women</brief_title>
  <official_title>A Pilot Study of Prophylactic Management of Lamotrigine for Bipolar Disorder in Pregnant Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pregnant women who are taking lamotrigine will be evaluated monthly during pregnancy&#xD;
      including a clinical evaluation and a blood draw for lamotrigine levels at each visit. Based&#xD;
      on the Therapeutic Drug Monitoring protocol, participant's lamotrigine dosing will be&#xD;
      adjusted as needed based on participant's blood levels compared to the reference&#xD;
      concentration that was obtained prior to pregnancy or early in pregnancy while clinically&#xD;
      stable. After delivery participant and participant's infants will be assessed for mood and&#xD;
      functioning at 1, 2, 4, and 6 weeks postpartum.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Studies have demonstrated that at least 80% of women who stop mood stabilizing medications&#xD;
      for pregnancy relapse psychiatrically. However, relapse is also quite common in women who&#xD;
      continue taking mood stabilizing medication with studies demonstrating approximately a 30-37%&#xD;
      relapse rate-most with depressive episodes. One likely explanation for the high relapse rate&#xD;
      of Bipolar Disorder during pregnancy despite continued mood stabilizing medication is&#xD;
      decreasing blood levels of mood stabilizing medications during the course of pregnancy.&#xD;
      Pregnancy induces both pharmacokinetic and pharmacodynamic changes, which can result in&#xD;
      decreased serum blood levels and decreased treatment efficacy. Therapeutic drug monitoring is&#xD;
      considered standard of care for a number of psychiatric medications. Therapeutic drug&#xD;
      monitoring can be an especially crucial guide to clinical treatment during pregnancy, but&#xD;
      remarkably, there are no established protocols for the monitoring of levels and dosing of&#xD;
      psychiatric medications in pregnancy. Most pregnant psychiatric patients are therefore&#xD;
      managed based on symptom recurrence. In contrast, there are established protocols for&#xD;
      monitoring blood levels and prophylactic management of antiepileptic medications for&#xD;
      epilepsy, including lamotrigine which is also a mood stabilizing medication. The&#xD;
      investigators will collect pilot data on the psychiatric outcomes, adverse events, and&#xD;
      obstetrical and infant outcomes of pregnant women with Bipolar Disorder who undergo&#xD;
      prophylactic therapeutic drug monitoring for a commonly used mood stabilizing medication&#xD;
      during pregnancy- lamotrigine. In the epilepsy literature, there is a published protocol for&#xD;
      lamotrigine management before, during, and after pregnancy for seizure control; the&#xD;
      investigators will use this protocol as a guide.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 3, 2018</start_date>
  <completion_date type="Anticipated">December 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Mood as assessed by The Edinburgh Postnatal Rating Scale</measure>
    <time_frame>Monthly, after enrollment, up to 10 months</time_frame>
    <description>Self-reported experience of depressive symptoms over the past 7 days, each item is scored 0-3 (0=not experiencing the symptom, 3=experiencing the symptom most of the time) yielding a total between 0 and 30. A score of 0-9 indicates little to no depressive symptoms and a score from 10-30 indicates significant depressive symptoms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Mood as assessed by The Young Mania Rating Scale</measure>
    <time_frame>Monthly, after enrollment, up to 10 months</time_frame>
    <description>Clinical interview that measures manic symptoms in the past 2 weeks, each item is scored 0-4 (0=absent, 4=fully present) yielding a total between 0 and 44. Any score above 0 indicates a possible manic episode.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Side Effect as assessed by the Udvalg for Kliniske Undersøgelser Side Effects Rating Scale</measure>
    <time_frame>Monthly, after enrollment, up to 10 months</time_frame>
    <description>Clinical interview that measures current, or in the past 72 hours, side effects of medication, each item is scored 0-3 (0=not or doubtfully present, 3=severe), yielding a total between 0 and 168. Any score above 0 indicates a possible causal relationship between medication and side effects.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Side Effect as assessed by the Frequency, Intensity, and Burden of Side Effects Rating Scale</measure>
    <time_frame>Monthly, after enrollment, up to 10 months</time_frame>
    <description>Self-reported frequency, intensity, and burden of side effects in the past week, each item is scored 0-6 (0=no side effects/impairment, 6=present all the time/intolerable/unable to function) yielding a total between 0 and 18. For each item, a score of 0-2 indicates treatment should continue, a score of 3-4 indicates the side effect should be addressed, and a score of 5-6 indicates a change in treatment is needed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Infant Habituation as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale</measure>
    <time_frame>At 1, 2, 4, and 6 weeks postpartum</time_frame>
    <description>Neurobehavioral assessment measuring infant's ability to shut down response to a stimulus, the item is scored 1-9, a low score indicates no decrement in response over 10 stimuli and a high score indicates a shut down of response after 1-2 stimuli</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Infant Attention as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale</measure>
    <time_frame>At 1, 2, 4, and 6 weeks postpartum</time_frame>
    <description>Neurobehavioral assessment measuring infant's response to a stimulus, the item is scored 1-9, a low score indicates no response and a high score indicates alerting to stimulus</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Infant Self-Regulation as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale</measure>
    <time_frame>At 1, 2, 4, and 6 weeks postpartum</time_frame>
    <description>Neurobehavioral assessment measuring infant's ability to self-regulate, the item is scored 1-9, a low score indicates the infant makes no attempt to quiet self and a high score indicates the infant consistently quiets self for sustained periods</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Infant Arousal as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale</measure>
    <time_frame>At 1, 2, 4, and 6 weeks postpartum</time_frame>
    <description>Neurobehavioral assessment measuring infant's arousal, the item is scored 1-9, a low score indicates a low level of arousal to all stimuli and a high score indicates the infant achieves insulated crying</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Infant Tonicity as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale</measure>
    <time_frame>At 1, 2, 4, and 6 weeks postpartum</time_frame>
    <description>Neurobehavioral assessment measuring infant's body tone, the item is scored 1-9, a low score indicates the infant is flaccid and a high score indicates the infant is hypertonic</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Infant Reflexes as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale</measure>
    <time_frame>At 1, 2, 4, and 6 weeks postpartum</time_frame>
    <description>Neurobehavioral assessment measuring infant's reflexes, the item is scored 1-5, a low score indicates no response and a high score indicates a strong response</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Infant Quality of Movement as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale</measure>
    <time_frame>At 1, 2, 4, and 6 weeks postpartum</time_frame>
    <description>Neurobehavioral assessment measuring infant's power and flexibility, the item is scored 1-5, a low score indicates no resistance/movement and a high score indicates strong resistance/movement</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Gestational Age at Birth in Weeks assessed by Review of the Infant Delivery Chart</measure>
    <time_frame>At 2 weeks postpartum visit, up to 15 minutes</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Birth Length in Inches assessed by Review of the Infant Delivery Chart</measure>
    <time_frame>At 2 weeks postpartum visit, up to 15 minutes</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Birth Weight in pounds assessed by Review of the Infant Delivery Chart</measure>
    <time_frame>At 2 weeks postpartum visit, up to 15 minutes</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>APGAR Score at 1 Minute assessed by Review of the Infant Delivery Chart</measure>
    <time_frame>At 2 weeks postpartum visit, up to 15 minutes</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>APGAR Score at 5 Minutes assessed by Review of the Infant Delivery Chart</measure>
    <time_frame>At 2 weeks postpartum visit, up to 15 minutes</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of Neonatal Intensive Care Unit Admission by Review of the Infant Delivery Chart</measure>
    <time_frame>At 2 weeks postpartum visit, up to 15 minutes</time_frame>
    <description>By reviewing the infant delivery chart, the outcome will be &quot;yes&quot; if the infant was admitted to the Neonatal Intensive Care Unit and &quot;no&quot; if the infant was not admitted</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Bipolar Disorder</condition>
  <condition>Major Depressive Disorder</condition>
  <condition>Schizo Affective Disorder</condition>
  <arm_group>
    <arm_group_label>Taking Lamotrigine</arm_group_label>
    <description>Lamotrigine (Lamictal), dosage will be based on a reference concentration of blood-serum levels</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lamictal</intervention_name>
    <description>Blood-serum levels will be checked monthly during pregnancy and reference concentration will be maintained</description>
    <arm_group_label>Taking Lamotrigine</arm_group_label>
    <other_name>Lamotrigine</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Pregnant women who are currently taking Lamotrigine for Bipolar Disorder, Major Depressive&#xD;
        Disorder, Schizoaffective Disorder, or another psychiatric illness, and plan to continue&#xD;
        throughout pregnancy.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  pregnant, prior or 20 weeks&#xD;
&#xD;
          -  currently taking Lamotrigine and plan to continue throughout pregnancy&#xD;
&#xD;
          -  history of Bipolar Disorder, Major Depressive Disorder, Schizoaffective Disorder or&#xD;
             other psychiatric illness, currently stable&#xD;
&#xD;
          -  may be taking other psychiatric medications&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  suicidal/clinically unstable&#xD;
&#xD;
          -  alcohol, marijuana, or other drug dependence in last 90 days&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lindsay Standeven, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kelsey Hannan</last_name>
    <phone>(443)583-4329</phone>
    <email>khannan1@jhmi.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>550 N Broadway</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kelsey Hannan</last_name>
    </contact>
    <investigator>
      <last_name>Lindsay Standeven, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Viguera AC, Whitfield T, Baldessarini RJ, Newport DJ, Stowe Z, Reminick A, Zurick A, Cohen LS. Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood stabilizer discontinuation. Am J Psychiatry. 2007 Dec;164(12):1817-24; quiz 1923. doi: 10.1176/appi.ajp.2007.06101639.</citation>
    <PMID>18056236</PMID>
  </reference>
  <reference>
    <citation>Newport DJ, Stowe ZN, Viguera AC, Calamaras MR, Juric S, Knight B, Pennell PB, Baldessarini RJ. Lamotrigine in bipolar disorder: efficacy during pregnancy. Bipolar Disord. 2008 May;10(3):432-6. doi: 10.1111/j.1399-5618.2007.00565.x.</citation>
    <PMID>18402631</PMID>
  </reference>
  <reference>
    <citation>Le Strat Y, Dubertret C, Le Foll B. Prevalence and correlates of major depressive episode in pregnant and postpartum women in the United States. J Affect Disord. 2011 Dec;135(1-3):128-38. doi: 10.1016/j.jad.2011.07.004. Epub 2011 Jul 29.</citation>
    <PMID>21802737</PMID>
  </reference>
  <reference>
    <citation>Barker ED, Kirkham N, Ng J, Jensen SK. Prenatal maternal depression symptoms and nutrition, and child cognitive function. Br J Psychiatry. 2013 Dec;203(6):417-21. doi: 10.1192/bjp.bp.113.129486. Epub 2013 Oct 10.</citation>
    <PMID>24115347</PMID>
  </reference>
  <reference>
    <citation>McPhie S, Skouteris H, Fuller-Tyszkiewicz M, Hill B, Jacka F, O'Neil A. Relationships between mental health symptoms and body mass index in women with and without excessive weight gain during pregnancy. Midwifery. 2015 Jan;31(1):138-46. doi: 10.1016/j.midw.2014.07.004. Epub 2014 Jul 19.</citation>
    <PMID>25086989</PMID>
  </reference>
  <reference>
    <citation>Kim HG, Mandell M, Crandall C, Kuskowski MA, Dieperink B, Buchberger RL. Antenatal psychiatric illness and adequacy of prenatal care in an ethnically diverse inner-city obstetric population. Arch Womens Ment Health. 2006 Mar;9(2):103-7. doi: 10.1007/s00737-005-0117-5. Epub 2005 Dec 29.</citation>
    <PMID>16380813</PMID>
  </reference>
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    <citation>Grigoriadis S, VonderPorten EH, Mamisashvili L, Tomlinson G, Dennis CL, Koren G, Steiner M, Mousmanis P, Cheung A, Radford K, Martinovic J, Ross LE. The impact of maternal depression during pregnancy on perinatal outcomes: a systematic review and meta-analysis. J Clin Psychiatry. 2013 Apr;74(4):e321-41. doi: 10.4088/JCP.12r07968.</citation>
    <PMID>23656857</PMID>
  </reference>
  <reference>
    <citation>Dennis CL, McQueen K. The relationship between infant-feeding outcomes and postpartum depression: a qualitative systematic review. Pediatrics. 2009 Apr;123(4):e736-51. doi: 10.1542/peds.2008-1629.</citation>
    <PMID>19336362</PMID>
  </reference>
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    <citation>Diego MA, Field T, Hernandez-Reif M, Cullen C, Schanberg S, Kuhn C. Prepartum, postpartum, and chronic depression effects on newborns. Psychiatry. 2004 Spring;67(1):63-80. doi: 10.1521/psyc.67.1.63.31251.</citation>
    <PMID>15139586</PMID>
  </reference>
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    <citation>Ashman SB, Dawson G, Panagiotides H, Yamada E, Wilkinson CW. Stress hormone levels of children of depressed mothers. Dev Psychopathol. 2002 Spring;14(2):333-49. doi: 10.1017/s0954579402002080.</citation>
    <PMID>12030695</PMID>
  </reference>
  <reference>
    <citation>Essex MJ, Klein MH, Cho E, Kalin NH. Maternal stress beginning in infancy may sensitize children to later stress exposure: effects on cortisol and behavior. Biol Psychiatry. 2002 Oct 15;52(8):776-84. doi: 10.1016/s0006-3223(02)01553-6.</citation>
    <PMID>12372649</PMID>
  </reference>
  <reference>
    <citation>Halligan SL, Herbert J, Goodyer IM, Murray L. Exposure to postnatal depression predicts elevated cortisol in adolescent offspring. Biol Psychiatry. 2004 Feb 15;55(4):376-81. doi: 10.1016/j.biopsych.2003.09.013.</citation>
    <PMID>14960290</PMID>
  </reference>
  <reference>
    <citation>Robertson E, Grace S, Wallington T, Stewart DE. Antenatal risk factors for postpartum depression: a synthesis of recent literature. Gen Hosp Psychiatry. 2004 Jul-Aug;26(4):289-95. doi: 10.1016/j.genhosppsych.2004.02.006.</citation>
    <PMID>15234824</PMID>
  </reference>
  <reference>
    <citation>Akman I, Kuscu K, Ozdemir N, Yurdakul Z, Solakoglu M, Orhan L, Karabekiroglu A, Ozek E. Mothers' postpartum psychological adjustment and infantile colic. Arch Dis Child. 2006 May;91(5):417-9. doi: 10.1136/adc.2005.083790. Epub 2006 Feb 1.</citation>
    <PMID>16452109</PMID>
  </reference>
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    <citation>Flynn HA, Davis M, Marcus SM, Cunningham R, Blow FC. Rates of maternal depression in pediatric emergency department and relationship to child service utilization. Gen Hosp Psychiatry. 2004 Jul-Aug;26(4):316-22. doi: 10.1016/j.genhosppsych.2004.03.009.</citation>
    <PMID>15234828</PMID>
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    <citation>McLearn KT, Minkovitz CS, Strobino DM, Marks E, Hou W. The timing of maternal depressive symptoms and mothers' parenting practices with young children: implications for pediatric practice. Pediatrics. 2006 Jul;118(1):e174-82. doi: 10.1542/peds.2005-1551.</citation>
    <PMID>16818531</PMID>
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    <citation>Grace SL, Evindar A, Stewart DE. The effect of postpartum depression on child cognitive development and behavior: a review and critical analysis of the literature. Arch Womens Ment Health. 2003 Nov;6(4):263-74. doi: 10.1007/s00737-003-0024-6.</citation>
    <PMID>14628179</PMID>
  </reference>
  <reference>
    <citation>Deligiannidis KM, Byatt N, Freeman MP. Pharmacotherapy for mood disorders in pregnancy: a review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. J Clin Psychopharmacol. 2014 Apr;34(2):244-55. doi: 10.1097/JCP.0000000000000087.</citation>
    <PMID>24525634</PMID>
  </reference>
  <reference>
    <citation>Fotopoulou C, Kretz R, Bauer S, Schefold JC, Schmitz B, Dudenhausen JW, Henrich W. Prospectively assessed changes in lamotrigine-concentration in women with epilepsy during pregnancy, lactation and the neonatal period. Epilepsy Res. 2009 Jul;85(1):60-4. doi: 10.1016/j.eplepsyres.2009.02.011. Epub 2009 Mar 9.</citation>
    <PMID>19272754</PMID>
  </reference>
  <reference>
    <citation>Polepally AR, Pennell PB, Brundage RC, Stowe ZN, Newport DJ, Viguera AC, Ritchie JC, Birnbaum AK. MODEL-BASED LAMOTRIGINE CLEARANCE CHANGES DURING PREGNANCY: CLINICAL IMPLICATION. Ann Clin Transl Neurol. 2014 Feb;1(2):99-106. doi: 10.1002/acn3.29.</citation>
    <PMID>24883336</PMID>
  </reference>
  <reference>
    <citation>Hirsch LJ, Weintraub D, Du Y, Buchsbaum R, Spencer HT, Hager M, Straka T, Bazil CW, Adams DJ, Resor SR Jr, Morrell MJ. Correlating lamotrigine serum concentrations with tolerability in patients with epilepsy. Neurology. 2004 Sep 28;63(6):1022-6. doi: 10.1212/01.wnl.0000138424.33979.0c.</citation>
    <PMID>15452293</PMID>
  </reference>
  <reference>
    <citation>Sabers A. Algorithm for lamotrigine dose adjustment before, during, and after pregnancy. Acta Neurol Scand. 2012 Jul;126(1):e1-4. doi: 10.1111/j.1600-0404.2011.01627.x. Epub 2011 Dec 9.</citation>
    <PMID>22150770</PMID>
  </reference>
  <reference>
    <citation>Clark CT, Klein AM, Perel JM, Helsel J, Wisner KL. Lamotrigine dosing for pregnant patients with bipolar disorder. Am J Psychiatry. 2013 Nov;170(11):1240-7. doi: 10.1176/appi.ajp.2013.13010006.</citation>
    <PMID>24185239</PMID>
  </reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>December 11, 2018</study_first_submitted>
  <study_first_submitted_qc>December 11, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 13, 2018</study_first_posted>
  <last_update_submitted>July 6, 2023</last_update_submitted>
  <last_update_submitted_qc>July 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lamotrigine</keyword>
  <keyword>Bipolar Disorder</keyword>
  <keyword>Major Depressive Disorder</keyword>
  <keyword>Schizo Affective Disorder</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
    <mesh_term>Bipolar Disorder</mesh_term>
    <mesh_term>Mood Disorders</mesh_term>
    <mesh_term>Psychotic Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lamotrigine</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 10, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/41/NCT03774641/Prot_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/NCT03774641
org study id: IRB00162134
nct id: NCT03774641
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Pregnant women who are taking lamotrigine will be evaluated monthly during pregnancy
      including a clinical evaluation and a blood draw for lamotrigine levels at each visit. Based
      on the Therapeutic Drug Monitoring protocol, participant's lamotrigine dosing will be
      adjusted as needed based on participant's blood levels compared to the reference
      concentration that was obtained prior to pregnancy or early in pregnancy while clinically
      stable. After delivery participant and participant's infants will be assessed for mood and
      functioning at 1, 2, 4, and 6 weeks postpartum.
Studies have demonstrated that at least 80% of women who stop mood stabilizing medications
      for pregnancy relapse psychiatrically. However, relapse is also quite common in women who
      continue taking mood stabilizing medication with studies demonstrating approximately a 30-37%
      relapse rate-most with depressive episodes. One likely explanation for the high relapse rate
      of Bipolar Disorder during pregnancy despite continued mood stabilizing medication is
      decreasing blood levels of mood stabilizing medications during the course of pregnancy.
      Pregnancy induces both pharmacokinetic and pharmacodynamic changes, which can result in
      decreased serum blood levels and decreased treatment efficacy. Therapeutic drug monitoring is
      considered standard of care for a number of psychiatric medications. Therapeutic drug
      monitoring can be an especially crucial guide to clinical treatment during pregnancy, but
      remarkably, there are no established protocols for the monitoring of levels and dosing of
      psychiatric medications in pregnancy. Most pregnant psychiatric patients are therefore
      managed based on symptom recurrence. In contrast, there are established protocols for
      monitoring blood levels and prophylactic management of antiepileptic medications for
      epilepsy, including lamotrigine which is also a mood stabilizing medication. The
      investigators will collect pilot data on the psychiatric outcomes, adverse events, and
      obstetrical and infant outcomes of pregnant women with Bipolar Disorder who undergo
      prophylactic therapeutic drug monitoring for a commonly used mood stabilizing medication
      during pregnancy- lamotrigine. In the epilepsy literature, there is a published protocol for
      lamotrigine management before, during, and after pregnancy for seizure control; the
      investigators will use this protocol as a guide.
observational model: Case-Only
time perspective: Prospective
measure: Change in Mood as assessed by The Edinburgh Postnatal Rating Scale
time frame: Monthly, after enrollment, up to 10 months
description: Self-reported experience of depressive symptoms over the past 7 days, each item is scored 0-3 (0=not experiencing the symptom, 3=experiencing the symptom most of the time) yielding a total between 0 and 30. A score of 0-9 indicates little to no depressive symptoms and a score from 10-30 indicates significant depressive symptoms.
measure: Change in Mood as assessed by The Young Mania Rating Scale
time frame: Monthly, after enrollment, up to 10 months
description: Clinical interview that measures manic symptoms in the past 2 weeks, each item is scored 0-4 (0=absent, 4=fully present) yielding a total between 0 and 44. Any score above 0 indicates a possible manic episode.
measure: Side Effect as assessed by the Udvalg for Kliniske Undersøgelser Side Effects Rating Scale
time frame: Monthly, after enrollment, up to 10 months
description: Clinical interview that measures current, or in the past 72 hours, side effects of medication, each item is scored 0-3 (0=not or doubtfully present, 3=severe), yielding a total between 0 and 168. Any score above 0 indicates a possible causal relationship between medication and side effects.
measure: Side Effect as assessed by the Frequency, Intensity, and Burden of Side Effects Rating Scale
time frame: Monthly, after enrollment, up to 10 months
description: Self-reported frequency, intensity, and burden of side effects in the past week, each item is scored 0-6 (0=no side effects/impairment, 6=present all the time/intolerable/unable to function) yielding a total between 0 and 18. For each item, a score of 0-2 indicates treatment should continue, a score of 3-4 indicates the side effect should be addressed, and a score of 5-6 indicates a change in treatment is needed.
measure: Change in Infant Habituation as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale
time frame: At 1, 2, 4, and 6 weeks postpartum
description: Neurobehavioral assessment measuring infant's ability to shut down response to a stimulus, the item is scored 1-9, a low score indicates no decrement in response over 10 stimuli and a high score indicates a shut down of response after 1-2 stimuli
measure: Change in Infant Attention as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale
time frame: At 1, 2, 4, and 6 weeks postpartum
description: Neurobehavioral assessment measuring infant's response to a stimulus, the item is scored 1-9, a low score indicates no response and a high score indicates alerting to stimulus
measure: Change in Infant Self-Regulation as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale
time frame: At 1, 2, 4, and 6 weeks postpartum
description: Neurobehavioral assessment measuring infant's ability to self-regulate, the item is scored 1-9, a low score indicates the infant makes no attempt to quiet self and a high score indicates the infant consistently quiets self for sustained periods
measure: Change in Infant Arousal as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale
time frame: At 1, 2, 4, and 6 weeks postpartum
description: Neurobehavioral assessment measuring infant's arousal, the item is scored 1-9, a low score indicates a low level of arousal to all stimuli and a high score indicates the infant achieves insulated crying
measure: Change in Infant Tonicity as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale
time frame: At 1, 2, 4, and 6 weeks postpartum
description: Neurobehavioral assessment measuring infant's body tone, the item is scored 1-9, a low score indicates the infant is flaccid and a high score indicates the infant is hypertonic
measure: Change in Infant Reflexes as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale
time frame: At 1, 2, 4, and 6 weeks postpartum
description: Neurobehavioral assessment measuring infant's reflexes, the item is scored 1-5, a low score indicates no response and a high score indicates a strong response
measure: Change in Infant Quality of Movement as assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale
time frame: At 1, 2, 4, and 6 weeks postpartum
description: Neurobehavioral assessment measuring infant's power and flexibility, the item is scored 1-5, a low score indicates no resistance/movement and a high score indicates strong resistance/movement
measure: Gestational Age at Birth in Weeks assessed by Review of the Infant Delivery Chart
time frame: At 2 weeks postpartum visit, up to 15 minutes
measure: Birth Length in Inches assessed by Review of the Infant Delivery Chart
time frame: At 2 weeks postpartum visit, up to 15 minutes
measure: Birth Weight in pounds assessed by Review of the Infant Delivery Chart
time frame: At 2 weeks postpartum visit, up to 15 minutes
measure: APGAR Score at 1 Minute assessed by Review of the Infant Delivery Chart
time frame: At 2 weeks postpartum visit, up to 15 minutes
measure: APGAR Score at 5 Minutes assessed by Review of the Infant Delivery Chart
time frame: At 2 weeks postpartum visit, up to 15 minutes
measure: Assessment of Neonatal Intensive Care Unit Admission by Review of the Infant Delivery Chart
time frame: At 2 weeks postpartum visit, up to 15 minutes
description: By reviewing the infant delivery chart, the outcome will be "yes" if the infant was admitted to the Neonatal Intensive Care Unit and "no" if the infant was not admitted
arm group label: Taking Lamotrigine
description: Lamotrigine (Lamictal), dosage will be based on a reference concentration of blood-serum levels
intervention type: Drug
intervention name: Lamictal
description: Blood-serum levels will be checked monthly during pregnancy and reference concentration will be maintained
arm group label: Taking Lamotrigine
other name: Lamotrigine
Serum
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lindsay Standeven, MD
role: Principal Investigator
affiliation: Johns Hopkins University
last name: Kelsey Hannan
phone: (443)583-4329
email: khannan1@jhmi.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
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responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
mesh term: Bipolar Disorder
mesh term: Mood Disorders
mesh term: Psychotic Disorders
mesh term: Lamotrigine
provided document: 