Neuropsychiatric Mechanisms of Change in Mentalization Based Treatment of Borderline Personality Disorder (MENTAB)

This study has been terminated.
Sponsor:
Collaborators:
Psychiatry Roskilde
University of Copenhagen
Psychiatric Epigenetics Laboratory, Institute of Psychiatry, UK
University of Southern Denmark
Psychoanalysis Unit, University College London, UK
Aarhus University Hospital
University College Zealand, Denmark
Research Division of Clinical Biochemistry, Koege Hospital, Denmark
Information provided by (Responsible Party):
Rune Andersen, Region Sjaelland
ClinicalTrials.gov Identifier:
NCT01720953
First received: October 26, 2012
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention
Borderline Personality Disorder
Other: Mentalization Based Therapy

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Neuropsychiatric Mechanisms of Change in Mentalization Based Treatment of Borderline Personality Disorder (MENTAB)

Resource links provided by NLM:


Further study details as provided by Region Sjælland:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • BDNF serum levels [ Time Frame: Assessed at baseline, and after 6 and 12 months ] [ Designated as safety issue: No ]
  • Salivary cortisol levels [ Time Frame: Assessed at baseline, and after 6 and 12 months ] [ Designated as safety issue: No ]
  • Neuropsychological test performance [ Time Frame: Assessed at baseline and after 12 months ] [ Designated as safety issue: No ]
    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.

  • Psychopathology [ Time Frame: Assessed before baseline, and after 6 and 12 months ] [ Designated as safety issue: No ]
    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)

  • Affect regulation [ Time Frame: Assessed at baseline, and after 6 and 12 months ] [ Designated as safety issue: No ]
    Measured by Affective Lability Scale (ALS-18), Barratt Impulsiveness Scale (BIS-11), Buss-Perry Aggression Questionnaire (BPAQ), Toronto Alexithymia Scale (TAS-20)


Biospecimen Retention:   Samples With DNA

Whole blood samples to measure DNA methylation and BDNF serum levels. Salivary samples to measure cortisol levels.


Estimated Enrollment: 100
Study Start Date: October 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Healthy control subjects
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.
Other: Mentalization Based Therapy
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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Fifty female patients diagnosed with BPD, who will undergo a year of intensive Mentalization Based Therapy at the Psychiatric Clinic Roskilde, Denmark, and a matched healthy control subjects matched on age, gender and socioeconomic status.

Criteria

Patients:

Inclusion Criteria:

  • Female patients between the ages 18 - 40 with a clinical diagnosis of Borderline Personality Disorder to undergo a year of Mentalization Based Therapy at the Psychiatric Clinic Roskilde.

Exclusion Criteria:

  • Severe comorbidity
  • Serious medical condition
  • Pregnancy

Healthy control subjects:

Inclusion Criteria:

  • Match patients on age, gender, and socioeconomic status.

Exclusion Criteria:

  • Any mental disorder
  • Serious medical condition
  • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01720953

Locations
Denmark
Psychiatric Research Unit, Region Zeland
Roskilde, Denmark, 4000
Sponsors and Collaborators
Rune Andersen
Psychiatry Roskilde
University of Copenhagen
Psychiatric Epigenetics Laboratory, Institute of Psychiatry, UK
University of Southern Denmark
Psychoanalysis Unit, University College London, UK
Aarhus University Hospital
University College Zealand, Denmark
Research Division of Clinical Biochemistry, Koege Hospital, Denmark
Investigators
Principal Investigator: Erik Simonsen, Professor, MD, Ph.D. Psychiatric Research Unit, Region Zealand, Denmark
Study Chair: Rune Andersen, Ph.D. Psychiatric Research Unit, Region Zealand, Denmark
  More Information

No publications provided

Responsible Party: Rune Andersen, Senior researcher, Ph.D., Region Sjaelland
ClinicalTrials.gov Identifier: NCT01720953     History of Changes
Other Study ID Numbers: SJ-311
Study First Received: October 26, 2012
Last Updated: July 24, 2014
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Ethics Committee

Keywords provided by Region Sjælland:
Borderline Personality Disorder
Mentalization Based Therapy
DNA methylation
BDNF
Cortisol
Neuropsychology

Additional relevant MeSH terms:
Personality Disorders
Borderline Personality Disorder
Mental Disorders

ClinicalTrials.gov processed this record on July 29, 2014