Borderline Personality DisorderNCT02134223
Methylation Status of BDNF Gene After Dialectical Behavior Therapy in BPD
A study testing Dialectical behavior therapy and Treatment as Usual: any other drug or psychotherapy offered to participants, except DBT in people with Borderline Personality Disorder, run by Mackay Memorial Hospital at 1 site in Taiwan.
Trial summary
Borderline personality disorder (BPD) is a chronic and debilitating syndrome associated with considerable morbidity, mortality, and high rates of medical and psychiatric utilization services. Read more about this study
- Who is it for?
- Ages 20 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Borderline Personality Disorder
- What is being tested?
- Dialectical behavior therapy and Treatment as Usual: any other drug or psychotherapy offered to participants, except DBT
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteTaiwan
- Study dates
- 20 Mar 2014to 26 Feb 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- patients meeting DSM-IV criteria for borderline personality disorder,
- 18-60 years of age
- have had at least two episodes of suicidal or non-suicidal self-injurious episodes in the past 5 years
- at least one of which is in the 3 months preceding enrollment
- agreement to participate in evaluation of the program
Who cannot join
- 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
- living outside of Taipei area
- having any serious medical condition likely to require hospitalization within the next year (e.g. cancer)
- having plans to leave the Taipei area in the next 1 year
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Changes in Methylation Status of BDNF Gene After Receiving Dialectical Behavior Therapy in Patients With Borderline Personality Disorder
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.
Read more
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.
Read the detailed 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:
- 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.
- 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.
- Known or unknown epigenetic drugs are also associated with alterations in methylation status in patient with BPD at cell level.
- Conditions
- Borderline Personality Disorder
- Being tested
- Dialectical behavior therapy, Treatment as Usual: any other drug or psychotherapy offered to participants, except DBT
- Medical subject headings
- Borderline Personality Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dialectical behavior therapyBehavioural
in standard DBT, we will employ all treatment modalities: a weekly individual (1 hour) and group (2 hours) session, available telephone consultation, and DBT consultation team.
DBT participants will be assigned to the next available individual therapist and relevant skills training group.
Groups have a minimum of four members before commencement and a maximum of twelve members. Entry to the skills group occurs only at the commencement of the next skills module.
Treatment as Usual: any other drug or psychotherapy offered to participants, except DBTOther
| Study group | Role | What they receive |
|---|---|---|
| dialectical behavior therapy | Experimental | Primary intervention group: receiving one year of dialectical behavior therapy Receives: Behavioral: Dialectical behavior therapy |
| treatment as usual | Placebo comparator | Comparison group: receiving one year of treatment as usual Receives: Other: Treatment as Usual: any other drug or psychotherapy offered to participants, except DBT |
| Receiving no treatment at all | No intervention | Healthy control group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Borderline Symptom Checklist (BSL-23)
To measure whether there were changes in scores of each symptoms regarding borderline personality disorder, such as number of times of attempting suicide, number of times of attempting self-harm, number of times of feeling emptiness, number of times of dissociations, number of times of risk-taking behaviors, number of times of substance or alcohol misuse etc.
Measured: Changes in scores of BSL-23 before treatment, and at 4, 8, 12 months after starting the treatment
Secondary outcomes (1)
The Patient Health Questionnaire (PHQ-9)
To measure changes in levels of patient health on a 4-point likert scale over questions of : feeling lack of interest? feeling sad or hopelessness, having problems sleeping, feeling fatigue or lack of energy, feeling poor appetite, or hyperphagia, feeling lack of confidence, unable to concentrate, or restlessness.
Measured: Changes in scores of PHQ-9 before and at 4, 8, 12 months after starting the treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2014 (estimated)
- Study start20 Mar 2014
- Primary completion25 Jan 2017
- Study completion26 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Borderline Personality DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mackay Memorial Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Science and Technology, Taiwan
- Responsible party
- Sponsor
- Investigators
- Shu-I Wu, MD, PhD, Principal investigator, Mackay Memorial Hospital, Taipei, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02134223
- Sponsor's protocol ID
- 13MMHIS257
- Other IDs
- MMH103-80, MOST 103-2314-B-195-002-MY2
- Status last verified
- Sep 2021
- First submitted
- 6 May 2014
- Last updated
- 5 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Storebo OJ, Stoffers-Winterling JM, Vollm BA, Kongerslev MT, Mattivi JT, Jorgensen MS, Faltinsen E, Todorovac A, Sales CP, Callesen HE, Lieb K, Simonsen E. Psychological therapies for people with borderline personality disorder. Cochrane Database Syst Rev. 2020 May 4;5(5):CD012955. doi: 10.1002/14651858.CD012955.pub2.
PubMed 32368793
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Changes in Methylation Status of BDNF Gene After Receiving Dialectical Behavior Therapy in Patients With Borderline Personality Disorder
- ClinicalTrials.gov ID
- NCT02134223
- Acronym / sponsor ID
- 13MMHIS257
- Conditions
- Borderline Personality Disorder
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Mackay Memorial HospitalUniversity, hospital or other
- Collaborators
- Ministry of Science and Technology, Taiwan
- Study start
- 20 Mar 2014 (actual)
- Primary completion
- 25 Jan 2017 (actual)
- Study completion
- 26 Feb 2020 (actual)
- First posted
- 9 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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:
- 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.
- 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.
- Known or unknown epigenetic drugs are also associated with alterations in methylation status in patient with BPD at cell level.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| dialectical behavior therapy | Experimental | Behavioral: Dialectical behavior therapyPrimary intervention group: receiving one year of dialectical behavior therapy |
| treatment as usual | Placebo comparator | Other: Treatment as Usual: any other drug or psychotherapy offered to participants, except DBTComparison group: receiving one year of treatment as usual |
| Receiving no treatment at all | No intervention | –Healthy control group |
Who may qualify
- Ages
- 20 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- patients meeting DSM-IV criteria for borderline personality disorder,
- 18-60 years of age
- have had at least two episodes of suicidal or non-suicidal self-injurious episodes in the past 5 years
- at least one of which is in the 3 months preceding enrollment
- agreement to participate in evaluation of the program
Key exclusion criteria (4 listed)
- 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
- living outside of Taipei area
- having any serious medical condition likely to require hospitalization within the next year (e.g. cancer)
- having plans to leave the Taipei area in the next 1 year
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dialectical behavior therapyin standard DBT, we will employ all treatment modalities: a weekly individual (1 hour) and group (2 hours) session, available telephone consultation, and DBT consultation team. DBT participants will be assigned to the next available individual therapist and relevant skills training group. Groups have a minimum of four members before commencement and a maximum of twelve members. Entry to the skills group occurs only at the commencement of the next skills module. | Behavioural | dialectical behavior therapy |
| Treatment as Usual: any other drug or psychotherapy offered to participants, except DBT | Other | treatment as usual |
Primary outcome
Borderline Symptom Checklist (BSL-23)
Time frame: Changes in scores of BSL-23 before treatment, and at 4, 8, 12 months after starting the treatment
To measure whether there were changes in scores of each symptoms regarding borderline personality disorder, such as number of times of attempting suicide, number of times of attempting self-harm, number of times of feeling emptiness, number of times of dissociations, number of times of risk-taking behaviors, number of times of substance or alcohol misuse etc.
1 secondary outcome
The Patient Health Questionnaire (PHQ-9)
Time frame: Changes in scores of PHQ-9 before and at 4, 8, 12 months after starting the treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2021.
- Derived from this study: PubMed 32368793Storebo OJ, Stoffers-Winterling JM, Vollm BA, Kongerslev MT, Mattivi JT, Jorgensen MS, Faltinsen E, Todorovac A, Sales CP, Callesen HE, Lieb K, Simonsen E. Psychological therapies for people with borderline personality disorder. Cochrane Database Syst Rev. 2020 May 4;5(5):CD012955. doi: 10.1002/14651858.CD012955.pub2.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shu-I Wu, MD, PhD principal investigator
Mackay Memorial Hospital, Taipei, Taiwan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dialectical behavior therapy and Treatment as Usual: any other drug or psychotherapy offered to participants, except DBT in people with Borderline Personality Disorder, run by Mackay Memorial Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Borderline Symptom Checklist (BSL-23) (time frame: Changes in scores of BSL-23 before treatment, and at 4, 8, 12 months after starting the treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02134223, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2021.