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Methylation Status of BDNF Gene After Dialectical Behavior Therapy in BPD

M

Mackay Memorial Hospital

Status

Completed

Conditions

Borderline Personality Disorder

Treatments

Behavioral: Dialectical behavior therapy
Other: Treatment as Usual: any other drug or psychotherapy offered to participants, except DBT

Study type

Interventional

Funder types

Other

Identifiers

NCT02134223
MMH103-80 (Other Grant/Funding Number)
MOST 103-2314-B-195-002-MY2 (Other Grant/Funding Number)
13MMHIS257

Details and patient eligibility

About

Borderline personality disorder (BPD) is a chronic and debilitating syndrome associated with considerable morbidity, mortality, and high rates of medical and psychiatric utilization services. Research focusing on finding a biological observable marker for the purpose of monitoring treatment effects has started to draw attention. Recent research has implicated that brain-derived neutrophilic factor (BDNF) might be a natural candidate for a biological correlate of early life stress. The alterations in levels of BDNF or BDNF methylation in BPD patients compared to general population, or pre- and post- psychotherapeutic treatment might indicate the consequence of epigenetic modification associated with stressful experience or suicide, and may later be able to explain the psychopathology or neuro-development of BPD.

Method: The investigators therefore propose this current randomized control trial to test whether epigenetic changes happen during and after DBT treatments, and not TAU. Proportions having suicide or non-suicidal self injurious behaviors will be followed and tested against changes in BDNF methylation levels. Other clinical symptoms will as be assessed, including suicidality, depression, hopelessness, quality of life, disability, service utilization, and function.

In the first to third years of this study, the investigators will aim to recruit 180 study and control subjects, to gather information, to collect biological samples, to give out one-year of psychotherapy per subject, to evaluate results before, during, and after treatment. In addition, the investigators also hope to explore the effects of known or unknown drugs associated with the change of DNA methylation at cell level.

Hypothesis:

Responders of participants who receive DBT will show greater decrease in BDNF methylation levels than patients receiving TAU.

Full description

Background: Borderline personality disorder (BPD) is a chronic and debilitating syndrome associated with considerable morbidity, mortality, and high rates of medical and psychiatric utilization services. The prevalence of BPD is around 1%-2% in general population. However, suicidality and self-injury are common, an estimated 69-80% of patients with BPD attempt suicide and a higher percentage engage in nonsuicidal self-injurious behavior. The rate of completed suicide in this group is appropriately 10%. Several Western literature have demonstrated the therapeutic effects of dialectical behavior therapy (DBT) in patients with BPD. However, research focusing on finding a biological observable marker for the purpose of monitoring treatment effects has started to draw attention. Recent research has implicated that brain-derived neutrophilic factor (BDNF) might be a natural candidate for a biological correlate of early life stress. The alterations in levels of BDNF or BDNF methylation in BPD patients compared to general population, or pre- and post- psychotherapeutic treatment might indicate the consequence of epigenetic modification associated with stressful experience or suicide, and may later be able to explain the psychopathology or neurodevelopment of BPD.

Such studies investigating associations of changes in methylation levels, with changes in depressive scores, hopelessness scores, impulsivity, or effects of psychotherapy have never been done in Asian countries. Little is known about the possible epigenetic changes related to Western psychological therapies for BPD patients in Asia.

Method: The investigators therefore propose this current randomized control trial to test whether epigenetic changes happen during and after DBT treatments, and not treatment as usual (TAU). Proportions having suicide or non-suicidal self injurious behaviors will be followed and tested against changes in BDNF methylation levels. Other clinical symptoms will as be assessed, including suicidality, depression, hopelessness, quality of life, disability, service utilization, and function. Inclusion criteria will be subjects who fulfill the Diagnostic Statistic Manual-IV (DSM-IV) criteria for BPD, 20-60 years of age, sign the informed consent, have had at least two episodes of suicidal or non-suicidal self-injurious episodes in the past 5 years, and at least one of which is in the 3 months preceding enrollment. The exclusion criteria include psychotic disorder, bipolar I disorder, severe physical illness, and mental retardation. Outcome measures and blood samples will be obtained at pre-treatment, 4-month, 8-month and post-treatment (12-month) during 1-year protocol. Using semi-structured interview and a battery of self-report forms, a range of symptoms and behaviors associated with BPD will be assessed. Outcome variables will be evaluated by blinded assessors.

In the first to third years of this study, the investigators will aim to recruit 180 study and control subjects, to gather information, to collect biological samples, to give out one-year of psychotherapy per subject, to evaluate results before, during, and after treatment. The TAU group would receive any therapy the patient could get excluding DBT. In addition, we also hope to explore the effects of known or unknown drugs associated with this project (such as decitabine, azacitidine, trichostatin A, valproic acid) on the change of DNA methylation at cell level. As a consequence, considering potential developments of biological correlates or medications as future evidences of treatments for BPD, this research is expected to take at least three years of investment.

Primary hypothesis:

Responders of participants who receive DBT will show greater decrease in BDNF methylation levels than patients receiving TAU.

Secondary Hypotheses:

  1. Participants who receive DBT and have greater reductions in the frequency and severity of suicidal and non-suicidal self-injurious behaviors will have different levels in BDNF methylations compared to those who didn't have as much improvement.
  2. Changes in scores or frequencies of borderline personality symptoms, depression, psychological symptoms, suicidal ideation, hopelessness, disability, and quality of life measures will be associated with changes in levels of BDNF proteins or BDNF methylations.
  3. Known or unknown epigenetic drugs are also associated with alterations in methylation status in patient with BPD at cell level.

Enrollment

60 patients

Sex

All

Ages

20 to 60 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

  1. patients meeting DSM-IV criteria for borderline personality disorder,
  2. 18-60 years of age
  3. have had at least two episodes of suicidal or non-suicidal self-injurious episodes in the past 5 years
  4. at least one of which is in the 3 months preceding enrollment
  5. agreement to participate in evaluation of the program

Exclusion criteria

  1. having a DSM-IV diagnosis of a psychotic disorder, bipolar I disorder, delirium, dementia, mental retardation, or a diagnosis of substance dependence in the preceding 30 days
  2. living outside of Taipei area
  3. having any serious medical condition likely to require hospitalization within the next year (e.g. cancer)
  4. having plans to leave the Taipei area in the next 1 year

Trial design

Primary purpose

Other

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Single Blind

60 participants in 3 patient groups, including a placebo group

dialectical behavior therapy
Experimental group
Description:
Primary intervention group: receiving one year of dialectical behavior therapy
Treatment:
Behavioral: Dialectical behavior therapy
treatment as usual
Placebo Comparator group
Description:
Comparison group: receiving one year of treatment as usual
Treatment:
Other: Treatment as Usual: any other drug or psychotherapy offered to participants, except DBT
Receiving no treatment at all
No Intervention group
Description:
Healthy control group

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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