<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/NCT01720953</url>
  </required_header>
  <id_info>
    <org_study_id>SJ-311</org_study_id>
    <nct_id>NCT01720953</nct_id>
  </id_info>
  <brief_title>Neuropsychiatric Mechanisms of Change in Mentalization Based Treatment of Borderline Personality Disorder (MENTAB)</brief_title>
  <acronym>MENTAB</acronym>
  <official_title>Neuropsychiatric Mechanisms of Change in Mentalization Based Treatment of Borderline Personality Disorder (MENTAB)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rune Andersen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Psychiatry Roskilde</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Copenhagen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Psychiatric Epigenetics Laboratory, Institute of Psychiatry, UK</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Southern Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Psychoanalysis Unit, University College London, UK</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Aarhus University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University College Zealand, Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Research Division of Clinical Biochemistry, Koege Hospital, Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Region Sjælland</source>
  <brief_summary>
    <textblock>
      Purpose:&#xD;
&#xD;
      Borderline personality disorder (BPD) is a complex psychiatric disease of uncertain aetiology&#xD;
      and pathogenesis. A key mechanism of disease susceptibility and treatment response could be&#xD;
      epigenetic changes in DNA methylation patterns. However, no study has yet demonstrated that&#xD;
      psychotherapy can exert its therapeutic effect through epigenetic mechanisms. The main aim of&#xD;
      this study is to analyze the promoter methylation pattern of genes considered to be related&#xD;
      to the development and psychopathology of BPD, in particular the brain-derived neurotrophic&#xD;
      factor (BDNF) and glucocorticoid receptor genes, and the effects of mentalization based&#xD;
      treatment (MBT) on changes. Associations to changes in BDNF serum levels and salivary&#xD;
      cortisol levels, as well as key components of BPD aetiology and core treatment targets in&#xD;
      MBT, will also be investigated. Should epigenetic mechanisms have importance for BPD&#xD;
      pathology and effects of treatment, there is potential use of DNA methylation patterns as&#xD;
      valid biomarker measures of diagnosis, prognosis, and treatment response.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      The formation and maintenance of symptoms in BPD is mediated through neuropsychiatric&#xD;
      mechanisms that can be affected through psychological treatment. Specifically, aberrant&#xD;
      epigenetic regulation of neuropsychiatric genes related to behavioural control and affect&#xD;
      regulation, as well as BDNF and cortisol levels, is ameliorated by therapeutic processes.&#xD;
&#xD;
      Method:&#xD;
&#xD;
      Fifty female patients diagnosed with BPD will undergo a year of intensive MBT that is&#xD;
      designed to target domains of BPD pathology. The patients will be assessed at baseline and&#xD;
      every 6 months over the treatment period. Matched healthy control subjects will be assessed&#xD;
      at 6 month intervals to compare changes in DNA methylation, BDNF serum levels, salivary&#xD;
      cortisol levels, and neuropsychological test performance. To link components of the&#xD;
      neuropsychiatric mechanisms underlying the onset of illness, course, and response to&#xD;
      treatment, patients will undergo assessment of clinical symptoms, comorbidity patterns and&#xD;
      psychosocial impairment. Patients and control subjects will at baseline undergo assessment&#xD;
      for childhood trauma, self-harm, suicidal behavior, early maladaptive schemas, and&#xD;
      personality traits, and within the 1-year study period also undergo continuous assessment for&#xD;
      changes in symptoms of dissociation, depression, and personality dysfunction.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Anticipated">December 2016</completion_date>
  <primary_completion_date type="Anticipated">December 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Promoter methylation pattern of genes considered to be related to the development and pathology of BPD, in particular the BDNF and glucocorticoid receptor genes</measure>
    <time_frame>Assessed at baseline, and after 6 and 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>BDNF serum levels</measure>
    <time_frame>Assessed at baseline, and after 6 and 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Salivary cortisol levels</measure>
    <time_frame>Assessed at baseline, and after 6 and 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Neuropsychological test performance</measure>
    <time_frame>Assessed at baseline and after 12 months</time_frame>
    <description>Assessed by a comprehensive battery of neuropsychological tests to measure both cognitive and emotion processing, including standard paper-and-pencil tests (WAIS-IV) and selected computerized tests (CANTAB, SuperLab and E-Prime). An interview will be conducted to assess autobiographical memory function.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Psychopathology</measure>
    <time_frame>Assessed before baseline, and after 6 and 12 months</time_frame>
    <description>Measured by Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD), Hamilton Rating Scale for Depression (HAM-D), Symptom Checklist-90-Revised (SCL-90-R), Severity Indices of Personality Problems (SIPP-118), and Dissociative Experiences Scale - Brief (DES-B)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Affect regulation</measure>
    <time_frame>Assessed at baseline, and after 6 and 12 months</time_frame>
    <description>Measured by Affective Lability Scale (ALS-18), Barratt Impulsiveness Scale (BIS-11), Buss-Perry Aggression Questionnaire (BPAQ), Toronto Alexithymia Scale (TAS-20)</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Borderline Personality Disorder</condition>
  <arm_group>
    <arm_group_label>Healthy control subjects</arm_group_label>
    <description>Matched healthy control subjects will be assessed at 6 month intervals to compare changes in DNA methylation, BDNF serum levels, salivary cortisol levels, and neuropsychological test performance. Healthy control subjects will within the 1-year study period also undergo continuous assessment for comparative changes in symptoms of dissociation, depression, and personality dysfunction.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Mentalization Based Therapy</intervention_name>
    <description>Fifty female patients diagnosed with BPD will undergo a year of intensive Mentalization Based Therapy that is designed to target domains of BPD pathology. The patients will be assessed at baseline and every 6 months over the treatment period.</description>
    <arm_group_label>Healthy control subjects</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood samples to measure DNA methylation and BDNF serum levels. Salivary samples to&#xD;
      measure cortisol levels.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Fifty female patients diagnosed with BPD, who will undergo a year of intensive&#xD;
        Mentalization Based Therapy at the Psychiatric Clinic Roskilde, Denmark, and a matched&#xD;
        healthy control subjects matched on age, gender and socioeconomic status.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Patients:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Female patients between the ages 18 - 40 with a clinical diagnosis of Borderline&#xD;
             Personality Disorder to undergo a year of Mentalization Based Therapy at the&#xD;
             Psychiatric Clinic Roskilde.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe comorbidity&#xD;
&#xD;
          -  Serious medical condition&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
        Healthy control subjects:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Match patients on age, gender, and socioeconomic status.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any mental disorder&#xD;
&#xD;
          -  Serious medical condition&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Erik Simonsen, Professor, MD, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Psychiatric Research Unit, Region Zealand, Denmark</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rune Andersen, Ph.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Psychiatric Research Unit, Region Zealand, Denmark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Psychiatric Research Unit, Region Zeland</name>
      <address>
        <city>Roskilde</city>
        <zip>4000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>October 26, 2012</study_first_submitted>
  <study_first_submitted_qc>November 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 2, 2012</study_first_posted>
  <last_update_submitted>July 24, 2014</last_update_submitted>
  <last_update_submitted_qc>July 24, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 25, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Region Sjælland</investigator_affiliation>
    <investigator_full_name>Rune Andersen</investigator_full_name>
    <investigator_title>Senior researcher, Ph.D.</investigator_title>
  </responsible_party>
  <keyword>Borderline Personality Disorder</keyword>
  <keyword>Mentalization Based Therapy</keyword>
  <keyword>DNA methylation</keyword>
  <keyword>BDNF</keyword>
  <keyword>Cortisol</keyword>
  <keyword>Neuropsychology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Personality Disorders</mesh_term>
    <mesh_term>Borderline Personality Disorder</mesh_term>
  </condition_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/NCT01720953
org study id: SJ-311
nct id: NCT01720953
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
Purpose:

      Borderline personality disorder (BPD) is a complex psychiatric disease of uncertain aetiology
      and pathogenesis. A key mechanism of disease susceptibility and treatment response could be
      epigenetic changes in DNA methylation patterns. However, no study has yet demonstrated that
      psychotherapy can exert its therapeutic effect through epigenetic mechanisms. The main aim of
      this study is to analyze the promoter methylation pattern of genes considered to be related
      to the development and psychopathology of BPD, in particular the brain-derived neurotrophic
      factor (BDNF) and glucocorticoid receptor genes, and the effects of mentalization based
      treatment (MBT) on changes. Associations to changes in BDNF serum levels and salivary
      cortisol levels, as well as key components of BPD aetiology and core treatment targets in
      MBT, will also be investigated. Should epigenetic mechanisms have importance for BPD
      pathology and effects of treatment, there is potential use of DNA methylation patterns as
      valid biomarker measures of diagnosis, prognosis, and treatment response.

      Hypothesis:

      The formation and maintenance of symptoms in BPD is mediated through neuropsychiatric
      mechanisms that can be affected through psychological treatment. Specifically, aberrant
      epigenetic regulation of neuropsychiatric genes related to behavioural control and affect
      regulation, as well as BDNF and cortisol levels, is ameliorated by therapeutic processes.

      Method:

      Fifty female patients diagnosed with BPD will undergo a year of intensive MBT that is
      designed to target domains of BPD pathology. The patients will be assessed at baseline and
      every 6 months over the treatment period. Matched healthy control subjects will be assessed
      at 6 month intervals to compare changes in DNA methylation, BDNF serum levels, salivary
      cortisol levels, and neuropsychological test performance. To link components of the
      neuropsychiatric mechanisms underlying the onset of illness, course, and response to
      treatment, patients will undergo assessment of clinical symptoms, comorbidity patterns and
      psychosocial impairment. Patients and control subjects will at baseline undergo assessment
      for childhood trauma, self-harm, suicidal behavior, early maladaptive schemas, and
      personality traits, and within the 1-year study period also undergo continuous assessment for
      changes in symptoms of dissociation, depression, and personality dysfunction.
observational model: Case-Control
time perspective: Prospective
measure: Promoter methylation pattern of genes considered to be related to the development and pathology of BPD, in particular the BDNF and glucocorticoid receptor genes
time frame: Assessed at baseline, and after 6 and 12 months
measure: BDNF serum levels
time frame: Assessed at baseline, and after 6 and 12 months
measure: Salivary cortisol levels
time frame: Assessed at baseline, and after 6 and 12 months
measure: Neuropsychological test performance
time frame: Assessed at baseline and after 12 months
description: Assessed by a comprehensive battery of neuropsychological tests to measure both cognitive and emotion processing, including standard paper-and-pencil tests (WAIS-IV) and selected computerized tests (CANTAB, SuperLab and E-Prime). An interview will be conducted to assess autobiographical memory function.
measure: Psychopathology
time frame: Assessed before baseline, and after 6 and 12 months
description: Measured by Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD), Hamilton Rating Scale for Depression (HAM-D), Symptom Checklist-90-Revised (SCL-90-R), Severity Indices of Personality Problems (SIPP-118), and Dissociative Experiences Scale - Brief (DES-B)
measure: Affect regulation
time frame: Assessed at baseline, and after 6 and 12 months
description: Measured by Affective Lability Scale (ALS-18), Barratt Impulsiveness Scale (BIS-11), Buss-Perry Aggression Questionnaire (BPAQ), Toronto Alexithymia Scale (TAS-20)
arm group label: Healthy control subjects
description: Matched healthy control subjects will be assessed at 6 month intervals to compare changes in DNA methylation, BDNF serum levels, salivary cortisol levels, and neuropsychological test performance. Healthy control subjects will within the 1-year study period also undergo continuous assessment for comparative changes in symptoms of dissociation, depression, and personality dysfunction.
intervention type: Other
intervention name: Mentalization Based Therapy
description: Fifty female patients diagnosed with BPD will undergo a year of intensive Mentalization Based Therapy that is designed to target domains of BPD pathology. The patients will be assessed at baseline and every 6 months over the treatment period.
arm group label: Healthy control subjects
Whole blood samples to measure DNA methylation and BDNF serum levels. Salivary samples to
      measure cortisol levels.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Erik Simonsen, Professor, MD, Ph.D.
role: Principal Investigator
affiliation: Psychiatric Research Unit, Region Zealand, Denmark
last name: Rune Andersen, Ph.D.
role: Study Chair
affiliation: Psychiatric Research Unit, Region Zealand, Denmark
facility: 
country: Denmark
responsible party type: Sponsor-Investigator
investigator affiliation: Region Sjælland
investigator full name: Rune Andersen
investigator title: Senior researcher, Ph.D.
mesh term: Personality Disorders
mesh term: Borderline Personality Disorder