<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/NCT02185547</url>
  </required_header>
  <id_info>
    <org_study_id>KWMP001</org_study_id>
    <nct_id>NCT02185547</nct_id>
  </id_info>
  <brief_title>Effects and Consequences for Mother and Child From Treatment for Depression</brief_title>
  <acronym>MAGDALENA</acronym>
  <official_title>Effects and Consequences for Mother and Child From Treatment for Depression, A Prospective Randomized, Placebo- Controlled, Trial With Internet-based Cognitive Behavior Therapy and Sertraline or Placebo for Moderate Depression in Pregnancy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Katarina Wide</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Karolinska University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study targets women with moderate depression during pregnancy. We aim to investigate the&#xD;
      direct effect of the newborn child and the long term consequences on the cognitive&#xD;
      developement on children who´s mother has been treated with CBT alone or in combination with&#xD;
      antidepressants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective is to study the direct neonatal effects and the long-term consequences&#xD;
      on cognitive development in children prenatal exposed to maternal sertraline treatment&#xD;
      compared to exposure to maternal depression treated with only ICBT.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Difficulties in recruiting participants.&#xD;
  </why_stopped>
  <start_date type="Actual">February 21, 2016</start_date>
  <completion_date type="Actual">November 4, 2019</completion_date>
  <primary_completion_date type="Actual">November 4, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cognitive development</measure>
    <time_frame>2 years</time_frame>
    <description>The differences in cognitive development at 2 years evaluated by the standard Bayley Scales of Infant and Toddler Development third edition (BSID-III)®.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>measure in MADRS_S</measure>
    <time_frame>12 weeks, 14 weeks and 30 weeks</time_frame>
    <description>a) Add-on effect of sertraline measured in difference i) in self-report of depressive symptoms (MADRS-S),ii) in rate of remission from depression (measured by diagnostic psychiatric interview with MADRS at -12weeks, 14 weeks, and 30 weeks (= 3 months postpartum) of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stresshormone level</measure>
    <time_frame>up to 3 months postpartum</time_frame>
    <description>Effects on levels of S-hCG, cytokines,</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacological assessment</measure>
    <time_frame>4, 14, 18 weeks</time_frame>
    <description>Plasma sertraline concentrations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacological assessment</measure>
    <time_frame>4, 14, 18 weeks</time_frame>
    <description>Pharmacokinetic variations in the metabolism of sertraline. Assess activity of enzymes regulating the metabolism of sertralin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacological assessment</measure>
    <time_frame>4, 14, 18 weeks</time_frame>
    <description>Genetic variations in the metabolism of sertraline. Assess concentration of sertralin and markers for metabolism of sertralin on specific regions of sertralin pathways.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacological assessment</measure>
    <time_frame>4, 14, 18 weeks</time_frame>
    <description>Effects on prolactin levels. Assess prolactin.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Pregnancy</condition>
  <condition>Moderate Depression</condition>
  <arm_group>
    <arm_group_label>ICBT in combination with sertraline treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Internet cognitive behavioral therapy in combination with sertraline treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ICBT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Only Internet cognitive behavioral treatment, no additional depression treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zoloft</intervention_name>
    <description>Sertraline treatment 25 mg</description>
    <arm_group_label>ICBT in combination with sertraline treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>ICBT</intervention_name>
    <description>Internet behavioral cognitive therapy only</description>
    <arm_group_label>ICBT</arm_group_label>
    <arm_group_label>ICBT in combination with sertraline treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female &gt; 18 years old&#xD;
&#xD;
          2. Pregnant, gestational week 9-21.&#xD;
&#xD;
          3. Verified moderate depression according to SCID-I with or without concomitant anxiety&#xD;
             disorder.&#xD;
&#xD;
          4. Signed informed consent&#xD;
&#xD;
          5. Able to understand the Swedish language orally and in written and able to use the&#xD;
             internet for the ICBT, including having succeded in filling out online questionnaires&#xD;
&#xD;
          6. Are willing to participate to all study visits&#xD;
&#xD;
          7. Plans to give birth at the Department of Obstetrics at Karolinska University Hospital,&#xD;
             Huddinge or at additional study site such as Norrland University Hospital (NUS), Umeå&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Known drug or alcohol abuse 2. Serious psychiatric disorder such as psychosis,&#xD;
             bipolar disorder, severe personality disorder, ADHD/ADD, autism or mental retardation)&#xD;
             and severe melancholic or psychotic depression.&#xD;
&#xD;
             3. Known idiosyncrasy to Zoloft or allergy to one of the Zoloft excipients 4. Ongoing&#xD;
             medication with SSRI, SNRI, TCA, mood-stabilizers, antiepileptic drugs ,psychotropic&#xD;
             drugs, tramadol, propafenon, tolbutamid, flekainid, psychostimulants and atomoxetine,&#xD;
             insulin or steroids 5. Any severe somatic disease that necessitate regular treatment&#xD;
             with systemic steroids, severe heart and lung disease, kidney disease, liver disease,&#xD;
             diabetes mellitus, or epilepsy with drug treatment.&#xD;
&#xD;
             6. Women who either during screening or treatment on self-assessment forms (MADRS-S: 4&#xD;
             or more points on question about suicidal ideation (question 9)) report symptoms of&#xD;
             severe suicidal thoughts or suicide plans will be contacted for structured suicide&#xD;
             risk assessment by telephone (by experienced staff from the unit for internet&#xD;
             psychiatry according to clinical routine). If judged necessary patients will be booked&#xD;
             for psychiatric assessment by study nurse. If acute assessment or care is judged&#xD;
             necessary, referral to psychiatric emergency departments will be made according to the&#xD;
             same routine as in regular care.&#xD;
&#xD;
        Also women, who contact the study personal and report symptoms of suicidal thoughts or&#xD;
        suicide plans will receive psychiatric assessment as specified above. Women who according&#xD;
        to psychiatric assessment have a high suicidal risk will be excluded from the study. These&#xD;
        women will be actively transferred into necessary psychiatric treatment as usual.&#xD;
&#xD;
        7. Other factors that are clinical significant and could jeopardize study results or its&#xD;
        intention, as judged by study psychiatrist or study obstetrician&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Karolinska University Hospital</name>
      <address>
        <city>Stockholm</city>
        <zip>14186</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <reference>
    <citation>Wide K, Winbladh B, Kallen B. Major malformations in infants exposed to antiepileptic drugs in utero, with emphasis on carbamazepine and valproic acid: a nation-wide, population-based register study. Acta Paediatr. 2004 Feb;93(2):174-6. doi: 10.1080/08035250310021118.</citation>
    <PMID>15046269</PMID>
  </reference>
  <reference>
    <citation>Wide K, Winbladh B, Tomson T, Sars-Zimmer K, Berggren E. Psychomotor development and minor anomalies in children exposed to antiepileptic drugs in utero: a prospective population-based study. Dev Med Child Neurol. 2000 Feb;42(2):87-92. doi: 10.1017/s0012162200000177. Erratum In: Dev Med Child Neurol 2000 May;42(5):356.</citation>
    <PMID>10698324</PMID>
  </reference>
  <reference>
    <citation>Pilo C, Wide K, Winbladh B. Pregnancy, delivery, and neonatal complications after treatment with antiepileptic drugs. Acta Obstet Gynecol Scand. 2006;85(6):643-6. doi: 10.1080/00016340600604625.</citation>
    <PMID>16752253</PMID>
  </reference>
  <reference>
    <citation>Wide K, Winbladh B, Tomson T, Kallen B. Body dimensions of infants exposed to antiepileptic drugs in utero: observations spanning 25 years. Epilepsia. 2000 Jul;41(7):854-61. doi: 10.1111/j.1528-1157.2000.tb00253.x.</citation>
    <PMID>10897157</PMID>
  </reference>
  <reference>
    <citation>Wide K, Henning E, Tomson T, Winbladh B. Psychomotor development in preschool children exposed to antiepileptic drugs in utero. Acta Paediatr. 2002;91(4):409-14. doi: 10.1080/080352502317371643.</citation>
    <PMID>12061356</PMID>
  </reference>
  <reference>
    <citation>Tomson T, Battino D, French J, Harden C, Holmes L, Morrow J, Robert-Gnansia E, Scheuerle A, Vajda F, Wide K, Gordon J. Antiepileptic drug exposure and major congenital malformations: the role of pregnancy registries. Epilepsy Behav. 2007 Nov;11(3):277-82. doi: 10.1016/j.yebeh.2007.08.015.</citation>
    <PMID>17996635</PMID>
  </reference>
  <reference>
    <citation>Fahnehjelm KT, Wide K, Ygge J, Hellstrom A, Tomson T, Winbladh B, Stromland K. Visual and ocular outcome in children after prenatal exposure to antiepileptic drugs. Acta Ophthalmol Scand. 1999 Oct;77(5):530-5. doi: 10.1034/j.1600-0420.1999.770509.x.</citation>
    <PMID>10551294</PMID>
  </reference>
  <reference>
    <citation>Forsberg L, Wide K, Kallen B. School performance at age 16 in children exposed to antiepileptic drugs in utero--a population-based study. Epilepsia. 2011 Feb;52(2):364-9. doi: 10.1111/j.1528-1167.2010.02778.x. Epub 2010 Nov 3.</citation>
    <PMID>21054354</PMID>
  </reference>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>July 6, 2014</study_first_submitted>
  <study_first_submitted_qc>July 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 2014</study_first_posted>
  <last_update_submitted>January 13, 2020</last_update_submitted>
  <last_update_submitted_qc>January 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska University Hospital</investigator_affiliation>
    <investigator_full_name>Katarina Wide</investigator_full_name>
    <investigator_title>M.D associated professor</investigator_title>
  </responsible_party>
  <keyword>women</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sertraline</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02185547
org study id: KWMP001
nct id: NCT02185547
lead sponsor: 
has dmc: No
This study targets women with moderate depression during pregnancy. We aim to investigate the
      direct effect of the newborn child and the long term consequences on the cognitive
      developement on children who´s mother has been treated with CBT alone or in combination with
      antidepressants.
The primary objective is to study the direct neonatal effects and the long-term consequences
      on cognitive development in children prenatal exposed to maternal sertraline treatment
      compared to exposure to maternal depression treated with only ICBT.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Cognitive development
time frame: 2 years
description: The differences in cognitive development at 2 years evaluated by the standard Bayley Scales of Infant and Toddler Development third edition (BSID-III)®.
measure: measure in MADRS_S
time frame: 12 weeks, 14 weeks and 30 weeks
description: a) Add-on effect of sertraline measured in difference i) in self-report of depressive symptoms (MADRS-S),ii) in rate of remission from depression (measured by diagnostic psychiatric interview with MADRS at -12weeks, 14 weeks, and 30 weeks (= 3 months postpartum) of treatment
measure: Stresshormone level
time frame: up to 3 months postpartum
description: Effects on levels of S-hCG, cytokines,
measure: Pharmacological assessment
time frame: 4, 14, 18 weeks
description: Plasma sertraline concentrations.
measure: Pharmacological assessment
time frame: 4, 14, 18 weeks
description: Pharmacokinetic variations in the metabolism of sertraline. Assess activity of enzymes regulating the metabolism of sertralin.
measure: Pharmacological assessment
time frame: 4, 14, 18 weeks
description: Genetic variations in the metabolism of sertraline. Assess concentration of sertralin and markers for metabolism of sertralin on specific regions of sertralin pathways.
measure: Pharmacological assessment
time frame: 4, 14, 18 weeks
description: Effects on prolactin levels. Assess prolactin.
arm group label: ICBT in combination with sertraline treatment
arm group type: Experimental
description: Internet cognitive behavioral therapy in combination with sertraline treatment
arm group label: ICBT
arm group type: Active Comparator
description: Only Internet cognitive behavioral treatment, no additional depression treatment
intervention type: Drug
intervention name: Zoloft
description: Sertraline treatment 25 mg
arm group label: ICBT in combination with sertraline treatment
intervention type: Behavioral
intervention name: ICBT
description: Internet behavioral cognitive therapy only
arm group label: ICBT
arm group label: ICBT in combination with sertraline treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
facility: 
country: Sweden
citation: Wide K, Winbladh B, Kallen B. Major malformations in infants exposed to antiepileptic drugs in utero, with emphasis on carbamazepine and valproic acid: a nation-wide, population-based register study. Acta Paediatr. 2004 Feb;93(2):174-6. doi: 10.1080/08035250310021118.
PMID: 15046269
citation: Wide K, Winbladh B, Tomson T, Sars-Zimmer K, Berggren E. Psychomotor development and minor anomalies in children exposed to antiepileptic drugs in utero: a prospective population-based study. Dev Med Child Neurol. 2000 Feb;42(2):87-92. doi: 10.1017/s0012162200000177. Erratum In: Dev Med Child Neurol 2000 May;42(5):356.
PMID: 10698324
citation: Pilo C, Wide K, Winbladh B. Pregnancy, delivery, and neonatal complications after treatment with antiepileptic drugs. Acta Obstet Gynecol Scand. 2006;85(6):643-6. doi: 10.1080/00016340600604625.
PMID: 16752253
citation: Wide K, Winbladh B, Tomson T, Kallen B. Body dimensions of infants exposed to antiepileptic drugs in utero: observations spanning 25 years. Epilepsia. 2000 Jul;41(7):854-61. doi: 10.1111/j.1528-1157.2000.tb00253.x.
PMID: 10897157
citation: Wide K, Henning E, Tomson T, Winbladh B. Psychomotor development in preschool children exposed to antiepileptic drugs in utero. Acta Paediatr. 2002;91(4):409-14. doi: 10.1080/080352502317371643.
PMID: 12061356
citation: Tomson T, Battino D, French J, Harden C, Holmes L, Morrow J, Robert-Gnansia E, Scheuerle A, Vajda F, Wide K, Gordon J. Antiepileptic drug exposure and major congenital malformations: the role of pregnancy registries. Epilepsy Behav. 2007 Nov;11(3):277-82. doi: 10.1016/j.yebeh.2007.08.015.
PMID: 17996635
citation: Fahnehjelm KT, Wide K, Ygge J, Hellstrom A, Tomson T, Winbladh B, Stromland K. Visual and ocular outcome in children after prenatal exposure to antiepileptic drugs. Acta Ophthalmol Scand. 1999 Oct;77(5):530-5. doi: 10.1034/j.1600-0420.1999.770509.x.
PMID: 10551294
citation: Forsberg L, Wide K, Kallen B. School performance at age 16 in children exposed to antiepileptic drugs in utero--a population-based study. Epilepsia. 2011 Feb;52(2):364-9. doi: 10.1111/j.1528-1167.2010.02778.x. Epub 2010 Nov 3.
PMID: 21054354
responsible party type: Sponsor-Investigator
investigator affiliation: Karolinska University Hospital
investigator full name: Katarina Wide
investigator title: M.D associated professor
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Sertraline