Epigenetic Regulation of BDNF in Major Depression

An observational study of Major Depressive Disorder, run by Chang Gung Memorial Hospital at 1 site in Taiwan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The investigators will (1) detect the associations between brain-derived neurotrophic factor (BDNF) DNA methylation, histone modification, depressive symptoms, suicidal behavior and antidepressant responses in major depressive disorder (MDD) patients, (2) check the correlation between blood BDNF protein and RNA and… Read more about this study

Who is it for?: Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Major Depressive Disorder
How many people: 110 participants
Where: 1 siteTaiwan
Study dates: Aug 2010to May 2013
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 18 to 60 years
All sexes
Healthy volunteers accepted
Adult

Study population: This 2-year study will be conducted in our clinical setting. By a semi-structured interview for DSM-IV criteria, a total of 160 subjectes (80 healthy controls and 80 patients with major depression) will be recruited in this study. In the first year (recruiting 40 healthy controls and 40 patients with major depression), the data of BDNF DNA methylation in all subjects will be collected. In the second year (recruiting another 40 healthy controls and 40 patients with major depression), the data of BDNF histone modification in all subjects will be collected and the mechanism of epigenetic regulation of BDNF in major depression will be discussed.

Who may be able to join

The clinical screening and assessment in patients with major depression：
40 major depression will be recruited in psychiatric inpatients according to DSM-IV criteria by a semi-structured interview. The assessment will be done by two senior psychiatrists. The intra-rater and inter-rater reliability will be done before this project started.
The patients had the ability to complete the written inform consent.
The choice of antidepressant drugs depended on the need of patients in natural treatment procedure. They included selective serotonin reuptake inhibitors (SSRI), eg. fluoxetine or paroxetine.
The 17-item Hamilton Depression Rating Scale (HAM-D) was used to assess severity of depression. The minimum baseline score of the 17-item HAM-D was 18.

Who cannot join

The patients had systemic diseases, including metabolic, heart, and liver diseases。
The patients had received any drugs before entering this protocol.
The patients were heavy smokers or dependent on alcohol.
The use of secondary generation anti-psychotic drugs and mood stabilizers.

Trial locations and contacts

1 site in 1 country.

Taiwan1 site

Department of Psychiatry, Chang Gung Memorial Hospital
Kaohsiung City, 833

Other trials in Taiwan

About this study

Official title: Epigenetic Regulation of Brain-Derived Neurotropic Factor (BDNF) in Patients With Major Depression

Read the detailed description

Brain-derived neurotrophic factor (BDNF) had been chosen as a candidate gene for a development of major depressive disorder (MDD). BDNF had been reported to have an important role on neuronal plasticity, axonal growth and connectivity, and participating in the local response to various types of neuronal stressors. BDNF also influences the differentiation of neurons.

In the past studies, the investigators had found that major depressive women had lower serum BDNF protein levels than healthy controls, and their BDNF levels became significantly increased after antidepressant treatments. In addition, some authors had found that reduced expression of BDNF was noted in postmortem brain of completed suicide subjects. Suicidal major depressive patients also had lower plasma BDNF levels than non-suicidal major depressive patients. These findings suggested that BDNF might play an important role in the suicidal behavior.

However, in past studies, the results did not fully explain why major depressive patients with same genotypes had different clinical expression, including the severity of depression, with/without suicide, and the treatment response. Recently, some papers found that there were relationships between epigenetic regulation, including DNA methylation and histone modification, and psychopathology of major depression. Therefore, we try to investigate the relationships between epigenetic regulation of BDNF and major depression.

Conditions: Major Depressive Disorder
Keywords: Major depression, BDNF, DNA methylation, Histone modification
Medical subject headings: Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01182103
Study group	Role	What they receive
Major depressive patients		Not described
Healthy subjects		Not described

What is being measured

The primary outcome is the main question the study is designed to answer.

Brain-derived Neurotrophic Factor (BDNF) DNA Methylation of Major Depressive Disorder (MDD) Patients and Healthy Controls
averaged percentage of methylation at each CpG site listed
Measured: 2 years
Histone Modification of MDD Patients Before and After Treatment and With Healthy Controls
Chromatin immunoprecipitation (ChIP) was used to measure histone modification. The unit of our given machine is relative quantification, and a higher value indicated increased histone modification. The detailed method could be found in:
Huebert DJ, Kamal M, O'Donovan A, Bernstein BE: Genome-wide analysis of histone modifications by ChIP-on-chip. Methods 2006; 40: 365-369.
Measured: 2 years

Secondary outcomes (1)

BDNF Levels of MDD Patients Before and After Treatment and Healthy Controls
Serum BDNF levels were measured. MDD patients received antidepressant treatment, a standard biological management. Nothing novel (such as experimental drugs or management) is introduced in the treatment, so the research design is observational (of standard treatment).
The choice of antidepressant drugs depended on the need of patients in natural treatment procedure. They included selective serotonin reuptake inhibitors (SSRI), eg. fluoxetine or paroxetine.
Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2010May 2013

First posted16 Aug 2010 (estimated)
Study startAug 2010
Primary completionJul 2012
Study completionMay 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
More trials run by Chang Gung Memorial HospitalThe sponsor's other registered studies.
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: Observational
Observational model: Case-control
Time perspective: Cross-sectional
Enrolment: 110 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01182103
Sponsor's protocol ID: NSC99-2628-B-182-002-MY2
Status last verified: Jul 2014
First submitted: 11 Aug 2010
Last updated: 15 Aug 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Major Depressive Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Epigenetic Regulation of Brain-Derived Neurotropic Factor (BDNF) in Patients With Major Depression
ClinicalTrials.gov ID: NCT01182103
Acronym / sponsor ID: NSC99-2628-B-182-002-MY2
Conditions: Major Depressive Disorder
Keywords: Major depression, BDNF, DNA methylation, Histone modification
Study type: Observational
Recruitment status: Completed
Enrolment: 110 participants (actual)
Lead sponsor: Chang Gung Memorial HospitalUniversity, hospital or other
Study start: Aug 2010
Primary completion: Jul 2012 (actual)
Study completion: May 2013 (actual)
First posted: 16 Aug 2010 (estimated)
Results: Posted 15 Aug 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Observational model: Case-control
Time perspective: Cross-sectional
Number of arms: 2

Arm	Type	Receives
Major depressive patients	–	–
Healthy subjects	–	–

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult
Study population: This 2-year study will be conducted in our clinical setting. By a semi-structured interview for DSM-IV criteria, a total of 160 subjectes (80 healthy controls and 80 patients with major depression) will be recruited in this study. In the first year (recruiting 40 healthy controls and 40 patients with major depression), the data of BDNF DNA methylation in all subjects will be collected. In the second year (recruiting another 40 healthy controls and 40 patients with major depression), the data of BDNF histone modification in all subjects will be collected and the mechanism of epigenetic regulation of BDNF in major depression will be discussed.

Key inclusion criteria (5 listed)

The clinical screening and assessment in patients with major depression：
40 major depression will be recruited in psychiatric inpatients according to DSM-IV criteria by a semi-structured interview. The assessment will be done by two senior psychiatrists. The intra-rater and inter-rater reliability will be done before this project started.
The patients had the ability to complete the written inform consent.
The choice of antidepressant drugs depended on the need of patients in natural treatment procedure. They included selective serotonin reuptake inhibitors (SSRI), eg. fluoxetine or paroxetine.
The 17-item Hamilton Depression Rating Scale (HAM-D) was used to assess severity of depression. The minimum baseline score of the 17-item HAM-D was 18.

Key exclusion criteria (4 listed)

The patients had systemic diseases, including metabolic, heart, and liver diseases。
The patients had received any drugs before entering this protocol.
The patients were heavy smokers or dependent on alcohol.
The use of secondary generation anti-psychotic drugs and mood stabilizers.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

Brain-derived Neurotrophic Factor (BDNF) DNA Methylation of Major Depressive Disorder (MDD) Patients and Healthy Controls
Time frame: 2 years
averaged percentage of methylation at each CpG site listed
Histone Modification of MDD Patients Before and After Treatment and With Healthy Controls
Time frame: 2 years
Chromatin immunoprecipitation (ChIP) was used to measure histone modification. The unit of our given machine is relative quantification, and a higher value indicated increased histone modification. The detailed method could be found in: Huebert DJ, Kamal M, O'Donovan A, Bernstein BE: Genome-wide analysis of histone modifications by ChIP-on-chip. Methods 2006; 40: 365-369.

1 secondary outcome

BDNF Levels of MDD Patients Before and After Treatment and Healthy Controls
Time frame: 2 years

Results and safety

Results posted to the registry on 15 Aug 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Major Depressive Patients	48	48
Healthy Subjects	62	62

Primary outcome: Brain-derived Neurotrophic Factor (BDNF) DNA Methylation of Major Depressive Disorder (MDD) Patients and Healthy Controls

Time frame: 2 years. Mean (Standard Deviation). Unit: percent

Measure	Major Depressive Patients n = 39	Healthy Subjects n = 62
CpG site 24	92 (5.0)	92 (3.0)
CpG site 57	75 (5.4)	75 (4.8)
CpG site 80	65 (7.6)	63 (6.2)
CpG site 134	87 (4.2)	86 (3.8)
CpG site 140	49 (23.2)	41 (24.7)
CpG site 177	93 (3.9)	94 (2.3)
CpG site 203	88 (5.2)	90 (2.9)
CpG site 217	61 (8.0)	51 (11.4)

Major Depressive Patients vs Healthy Subjects: p <0.05, t-test, 2 sided

Population analysed: Only 39 out of the 48 MDD patients provided enough blood sample for this analysis.

Primary outcome: Histone Modification of MDD Patients Before and After Treatment and With Healthy Controls

Time frame: 2 years. Mean (Standard Deviation). Unit: relative quantification

Measure	Healthy Subjects n = 39	Major Depressive Patients Before Treatment n = 37	Major Depressive Patients After Treatment n = 37
BDNF promotor I acetyl-H3	3.5610 (2.79865)	.3124 (.53231)	.4321 (.32039)
BDNF promotor I acetyl-H4	2.6346 (2.66175)	.3784 (.54543)	.4659 (.62056)
BDNF promotor IV acetyl-H3	1.6356 (2.33692)	.4059 (.43157)	.4303 (.70365)
BDNF promotor IV acetyl-H4	2.2795 (2.66175)	.4676 (.54543)	.4988 (.62056)
BDNF promotor X acetyl-H3	3.8960 (1.94450)	.2564 (.36703)	.3640 (.34533)
BDNF promotor X acetyl-H4	1.7433 (2.66175)	.2105 (.30502)	.2540 (.53050)

Healthy Subjects vs Major Depressive Patients Before Treatment vs Major Depressive Patients After Treatment: p <0.05, t-test, 2 sided

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Major Depressive Patients	0 of 48 (0%)	0 of 48 (0%)	Not reported
Healthy Subjects	0 of 62 (0%)	0 of 62 (0%)	Not reported

Limitations and caveats (from the sponsor): Limited funding prevented all samples from receiving all analyses.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Major Depressive Disorder

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Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
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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.

Tiao-Lai Huang, M.D. principal investigator

Chang-Gung Memorial Hospital, Kaohsiung

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Major Depressive Disorder, run by Chang Gung 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 15 Aug 2014. 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. 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?

Yes. Results are posted in the registry (first posted 15 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Brain-derived Neurotrophic Factor (BDNF) DNA Methylation of Major Depressive Disorder (MDD) Patients and Healthy Controls (time frame: 2 years). The study lists 2 primary outcomes in all. 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 NCT01182103.

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 15 Aug 2014.